Fibrinogen and platelet contributions to clot formation

Abstract

BACKGROUND Thromboelastography (TEG) is used to diagnose perturbations in clot formation and lysis that are characteristic of acute traumatic coagulopathy (ATC). With novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to clot formation can be elucidated to tailor resuscitation and thromboprophylaxis. We sought to describe the longitudinal contributions of fibrinogen and platelets to clot strength after injury, hypothesizing that low levels of functional fibrinogen and a low contribution of fibrinogen to clot strength on admission would be associated with coagulopathy, increased transfusion requirements, and worse outcomes. METHODS 603 longitudinal plasma samples were prospectively collected from 251 critically-injured patients at a single Level 1 Trauma Center from 0–120h. TEG maximal amplitude (MA), FF MA, FF levels (FLEV), von Clauss fibrinogen, and standard coagulation measures were performed in parallel. Percentage contributions of FF (%MAFF) and platelets (%MAplatelets) were calculated as each MA divided by overall kaolin TEG MA. RESULTS Coagulopathic patients (INR>=1.3) had significantly lower admission %MAFF than non-coagulopathic patients (24.7% vs. 31.2%, p<0.05). Patients requiring plasma transfusion had a significantly lower admission %MAFF (26.6% vs. 30.6%, p<0.05). Higher admission %MAFF was predictive of reduced mortality (HR 0.815, p<0.001). %MAplatelets was higher than %MAFF at all time points, decreased over time, and stabilized at 72 hours (69.4% at 0h, 56.2% at 72h). In contrast, %MAFF increased over time and stabilized at 72 hours (30.6% at 0h, 43.8% at 72). CONCLUSION FF TEG affords differentiation of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma transfusion were associated with a lower %MAFF. Despite this importance of fibrinogen, platelets had a greater contribution to clot strength at all time points after injury. This suggests that attention to these relative contributions should guide resuscitation and thromboprophylaxis, and that antiplatelet therapy may be of under-recognized importance to thromboprophylaxis after trauma. LEVEL OF EVIDENCE Level IV; prognostic

Microparticles impact coagulation after traumatic brain injury

“…Using this technology, human studies have shown that these tests are able to detect hypercoagulable states missed by common coagulation parameters such as plasma prothrombin time or activated partial thromboplastin time [34], and furthermore, that increased clot firmness on admission thromboelastography predicts increased rates of pulmonary embolism [35], highlighting the clinical importance of these tests. In addition, similar to our murine study, other human studies have shown that platelet contribution to clot strength steadily decreases over the 72 h after trauma, with a resulting increase in fibrinogen contribution [31]. Animal models have investigated altered platelet function after head injury [36]; however, our study is the first to demonstrate similar temporal changes in coagulation, specifically the platelet contribution to clot strength, after TBI using thromboelastometry in a murine model.…”

“…MPs were isolated as described in section 2.5. Percent of platelet contribution (%MCF-Platelet) was calculated by the equation: (EXTEM MCF – FIBTEM MCF )/EXTEM MCF , similar to the methods used by Kornblith et al [31]. For NATEM analysis, sham mice ( n = 9) and TBI mice at 10 min ( n = 7), 24 h ( n = 10), and 72 h ( n = 11) were used.…”

Tranexamic acid

“…In trauma, patients with lower functional fibrinogen had greater had greater transfusion requirements and higher mortality. [25] Rourke demonstrated that fibrinogen is rapidly depleted after trauma and that low fibrinogen levels predicted increased mortality at 24 hours. [26] Table 4 lists studies of fibrinogen depletion in trauma.…”

Trauma-Induced Coagulopathy

“…Finally, in the propagation phase, the platelet now adhered to the damaged endovasculature, acts as a foundation for thrombin conversion of fibrinogen and eventual strengthening of the hemostatic clot. Kornblith et al [32] used viscoelastic testing to determine contributions of fibrinogen and platelets to maximum clot firmness in 251 trauma patients (median ISS 9, BD −3.1, INR 1.1). In this cohort, platelets contributed 69.5 % and fibrinogen 30.5 % to clot strength.…”

“…Though viscoelastic testing is “poised to replace traditional plasma-based tests in the diagnosis of perturbations in clot formation and lysis characteristic of ATC” [32], it still has many limitations. Traditional TEG as an indicator of whole blood coagulation can be improved upon by modifications that result in faster turnaround times and more specific information as to which component of coagulation is dysfunctional or deficient.…”