Coagulation Testing in Trauma Patients
by Donna Castellone, MS, MT(ASCP)S • June 08, 2023
Introduction:
Trauma is a source of 28.4 million emergency visits per year according to the Centers for Disease Control. These injuries range from ankle sprain to multi-organ, critically ill patients with comorbidities.1 Up to 40% of prehospital deaths are attributed to traumatic injury with the leading cause being uncontrolled hemorrhage due to coagulation dysfunction. The major contributors to coagulation dysfunction are hypothermia, acidosis and resuscitative hemodilution, these may actually be present upon admission to the hospital. This can lead to increased blood transfusions; longer hospital stays and higher mortality. It is important for early recognition of any coagulopathy.2
Hypothermia and acidosis are the most important risk factors in trauma patients because they cause a dramatic reduction in the enzymatic activities of clotting factors. This is further complicated in patients receiving massive transfusions due to hemodilution or depletion of coagulation factors making these patients at a greater risk for developing disseminated intravascular coagulation (DIC) which in turn contributes to microvascular thrombosis and fibrinolysis.3
The abnormal coagulation process attributed to trauma is trauma induced coagulopathy (TIC). Initially, hypocoagulability is present which results in bleeding followed by hypercoagulability resulting in venous thrombosis and multiple organ failure.4
Pathophysiology of Trauma Induced Coagulopathy:
Several pathophysiological mechanisms are the underlying cause for TIC. Issues that contribute are tissue injury and shock. These synergistically provoke endothelial, immune system, platelet and clotting activation, which are accentuated by the 'lethal triad' (coagulopathy, hypothermia and acidos).4 Coagulopathy occurs mostly in the acute phase of trauma and consists of hyperfibrinolysis and consumption.5
Trauma-induced coagulopathy is generated by the following pathophysiological mechanisms. It begins with activation of the coagulation system by procoagulants in circulation. The platelet derived microparticles are leukocyte, erythrocyte and endothelial derived and are released during the acute phase of trauma. Tissue factor is also exposed on the membrane of some microparticles which may be reflected in the elevation of tissue factor antigen levels. In severe trauma, injured organs may also release microparticles.5
The impairment of endogenous anticoagulant activity along with thrombin generation in the systemic circulation also occurs. In severe trauma, the endogenous anticoagulant activities are immediately impaired, and dysregulation of coagulation activation is observed. This includes antithrombin and the TM-protein C pathway.5 Antithrombin has also been reported at low levels in severe trauma, as well as a decrease in protein C. Therefore, the anticoagulation ability of the TM-protein C pathway is impaired with resultant dysregulation of thrombin generation.6 The half-life of thrombin is short making measurement of plasma concentration difficult, however other elevated levels of other markers including soluble fibrin and fibrinopeptide A reflect the direct action of thrombin on fibrinogen resulting in fibrin formation.5
Severe trauma can result in hyperfibrinogenolysis. This is a combination of fibrinolysis and fibrinogenolysis. This is caused by the acute release of tissue-plasminogen activator (t-PA) along with coagulation activation.5 T-PA catalyzes the cleavage of plasminogen to plasma which in turn initiates fibrin and fibrinogen degradation in plasma. The Weibel-Palade body is the main source of t-PA and shock trauma can stimulate the endothelial cells and induce the release of t-PA which in turn induces hyperfibrinogenolysis.7
During coagulation activation and hyperfibrinogenolysis consumption of coagulation factors and platelets occur. Plasma fibrinogen level decreases earlier than other coagulation factors and is seen by an increase in both PT and aPTT. Infusions also result in the dilution of fibrinogen. Other coagulation factors cannot compensate for the role of fibrinogen as a precursor of fibrin. As a result, massive bleeding may occur with a poor outcome. The decrease in factors correlate with the severity of trauma. Factor V decreases more than any other factor.5 In the consumptive coagulopathy, platelets are activated via signals that include collagen in the sub-endothelial matrix binding to glycoprotein VI, von Willebrand factor and glycoprotein Ib.2
Trauma induced coagulopathy is a disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype. In DIC both bleeding and clotting can occur. In trauma induced DIC it is different than DIC with thrombosis. Coagulation activation is observed in both types, however plasma PAI suppresses fibrinolysis in DIC with the thrombotic phenotype, in TIC fibrinogenolysis is activated by t-PA in TIC. In the acute phase of trauma, it contributes to massive bleeding and death.8
Coagulation Testing in the Trauma Patient
The most common panel used to evaluate patients with trauma includes platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT) and fibrinogen level.3 There are no set standard tests to diagnosis a coagulopathy in trauma patients.
Platelets
Trauma patients present with thrombocytopenia, frequently due to a quantitative abnormality versus a qualitative abnormality. A major source of this is because of hemodilution due to massive blood transfusion and IV fluids. This occurs slowly due to having 30-40% of platelets stored in the spleen. Coagulation proteins will decrease quicker. Hypothermia and acidosis impact platelet adhesion and aggregation leading to a qualitative disorder of platelets. Available testing for this is difficult, the PFA-100 lacks support for use in trauma patients. Testing for secretion and adhesion requires platelet aggregation.3
Prothombin Time (PT):
Trauma patients who receive massive transfusions of packed red blood cells (PRBC) develop hemodilution of clotting factors. PRBC lacks the labile clotting factors of FV and FVIII. An isolated PT is not usually associated with a significant bleed, unless the PT/INR is prolonged more than 1.8 times the control value. At that point the aPTT will also be prolonged.3 Trauma patients experiencing acidosis will have a prolonged PT due to the decreased activity of VIIa on phospholipid levels by about 90%.2
Activated Partial Thromboplastin Time (aPTT)
The aPTT is more susceptible to hemodilution than the PT, it will appear after the patient receives 10-12 units of PRBC. An isolated aPTT is not a significant predictor of bleeding unless prolonged 1.8 time the control, and this will also prolong the PT.3 In acidotic trauma patients a prolonged aPTT will be seen due to the decrease in coagulation factors.2
Fibrinogen Level
Fibrinogen is an acute phase reactant, which results in elevated levels in times of stress, trauma and inflammation, so initially in trauma fibrinogen levels may be high. However, a consumption of clotting proteins along with hemodilution, fibrinogen levels can decrease. Levels of less than 80mg/dl is associated with a prolonged PT-INR and aPTT. A level below 50mg/dl is usually associated with bleeding.3
Hyperfibrinogenolysis induced by coagulation activation will also present with elevated D-dimer and fibrinogen degradation product (FDP). In the acute phase of trauma PAI activity has not yet increased enough, but the consumption of α2-plasmin inhibitor accelerates the dysregulation of fibrino(geno)lysis.5
Viscoelastic tests:
The cell-based model of hemostasis looks at the phases of initiation, amplification and propagation. These phases are regulated by properties of coagulation proteins, the surface of cells as well as receptors. Testing using either ROTEM or Thromboelastography (TEG) looks at the entire process and can guide care in trauma patients.2 The turnaround time for basic coagulation testing in trauma patients (platelet count, PT, aPTT and fibrinogen) in most of clinical laboratories offering this test is about 60 minutes. These tests may guide prompt hemostatic monitoring and therapy in trauma patients.3
ROTEM looks at the entire coagulation picture which includes clotting time formation, as well as speed and strength of the clot and fibrinolysis. This information has made it important in diagnosis of TIC and the prediction of transfusion and guiding the use of blood products.2 TEG testing is considered rapid point of care testing and takes less than 40 minutes. Both methods can provide rapid results but they come with caveats such as the time from blood draw to test, operator variability, time to test result, and implementation of testing.3 TEG and ROTEM have limited sensitivity in reflecting platelet dysfunction and moderate fibrinolysis.2 In the appropriate clinical setting, these tests may aid in the efficient utilization and reduction of blood products.
Conclusion:
It is important when performing a laboratory testing on a trauma patient that underlying health issues, mechanism of injury as well as the patient's history should be considered. Age, comorbidities and if the patient is on anticoagulation should be factored into the type of laboratory testing used as well as how what tests will be helpful to aid the trauma patient in their management and recovery.
Being able to diagnosis coagulopathy in trauma patients enables the restoration of hemostasis and the avoidance of possible life-threatening complications.
References:
- Arvind Venkat, The Value of Laboratory Testing in the Trauma Patient, TRAUMA REPORTS, Jan 2009, https://www.reliasmedia.com/articles/16688-the-value-of-laboratory-testing-in-the-trauma- patient
- Wenjun Z. Martini, Coagulation complications following trauma Military Medical Research volume 3, Article number: 35 (2016).
- Ali Gahbali*, Tarek Jazearly, Radhakrishnan Ramchandren, and Martin H Bluth. Applications of Coagulation Testing and Methodology in the Trauma Patient. Research & Reviews: Journal of Medical and Health Sciences, 28 November 2013,
- Moore, E.E., Moore, H.B., Kornblith, L.Z. et al. Trauma-induced coagulopathy. Nat Rev Dis Primers 7, 30 (2021).
- Mineji Hayakawa, Pathophysiology of trauma-induced coagulopathy: disseminated intravascular coagulation with the fibrinolytic phenotype Journal of Intensive Care volume 5, Article number: 14 (2017)
- Yanagida Y, Gando S, Sawamura A, Hayakawa M, Uegaki S, Kubota N, et al. Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock. Surgery. 2013;154:48–57.
- Huber D, Cramer EM, Kaufmann JE, Meda P, Masse JM, Kruithof EK, et al. Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in human endothelial cells both in vitro and in vivo. Blood. 2002;99:3637–45.
- Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A. Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study. Semin Thromb Hemost. 2015;41:35–42.