Will Thromboelastography Replace INR?

"The days of pounding fresh frozen [plasma] in people who are on Coumadin are over.” — Lawrence Lottenberg, MD, trauma surgeon.

Prothrombin time (PT) and the international normalized ratio (INR) were initially developed to assess adequacy of pharmacologic anticoagulation and eventually used to evaluate coagulation disorders.

The PT/INR test detects deficiencies in the extrinsic pathway of the coagulation cascade, specifically factors II, VII, IX, X, and somewhat I. Because these are vitamin K-dependent factors, INR is useful to assess the anticoagulant activity of warfarin and make decisions regarding dosing adjustments.

Because the vitamin K-dependent coagulation factors have varying half-lives, with factor II being the longest at up to 72 hours, the use of INR poses a potential problem for patients who require surgical intervention or invasive procedures. Depending on the nature of the intervention, the approach to management may vary.

In a scheduled procedure, the patient may undergo a “warfarin holiday” while bridging with a parenteral anticoagulant and then reinitiating warfarin after the procedure. In an emergent situation, however, a patient is given blood products mainly comprised of either fresh frozen plasma (FFP), which contains all of the vitamin K-dependent factors, or prothrombin complex concentrates (PCC) in order to “reverse” INR.¹

Is INR a true measurement of how a patient’s blood is clotting? Do patients in emergent situations really need to receive blood products, which have been associated with increased morbidity and mortality, or PCC products, which are extremely costly?

Unfortunately, INR is performed in vitro on platelet-poor plasma and can only provide a measure of time before initial thrombin generation. It is also taken at a single point in time and does not consider the patient’s evolving coagulation status.

Meanwhile, thromboelastography (TEG) is a real-time viscoelastic analysis of whole blood. It was first patented in the early 1980s and was mainly used intraoperatively for patients undergoing cardiopulmonary bypass, though it was also used to evaluate coagulation status in liver transplant patients.

TEG offers many advantages over standard coagulation tests, as it includes information regarding fibrin formation, initial clotting time, time to maximum clotting, clotting rapidity, clot strength, clot retraction, and fibrinolysis.²

TEG analysis is actually quite simple. Essentially, whole blood is placed in a cuvette and a pin is inserted. As the cup spins, the viscosity of the blood is measured and a trace is produced, in which the x-axis is time and the y-axis is clot formation.

Some key measurements of TEG include:

• R time: The time it initially takes the clot to start forming. A prolonged R time indicates a deficiency in clotting factors.
• Alpha angle: The speed at which the clot is forming. A depressed alpha angle indicates a deficit or dysfunction in fibrinogen.
• Max amplitude (MA): The total clot strength. A lower MA indicates a platelet deficiency or dysfunctionality. Of note, TEG has the ability to perform additional platelet mapping studies, which may provide more information in patients taking platelet-inhibitors.
• Lysis 30 (LY₃₀): The amount of clot that is broken down or “lysed” over the 30 minutes following formation. An increased LY₃₀ is suggestive of a hyperfibrinolytic state.

Results from TEG analysis may be available in similar time as INR, if not earlier.

Some limitations of TEG include:

• Von Willebrand disease
• Factor V Leiden thrombophilia
• Heparin-induced thrombocytopenia
• Lupus anticoagulant
• Protein C and protein S deficiency

Because TEG measures the capability of whole blood to make and sustain clot formation, it provides a bigger picture of coagulation status compared to the INR. Patients with an elevated INR who show normal hemostasis on TEG may not need to be unnecessarily exposed to blood products, break the bank with PCC, or have delayed procedures.

Although warfarin management in the perioperative setting remains controversial and should be approached on a case-by-case basis that considers risks and benefits, guidelines continue to recommend using INR to guide decisions. As more facilities acquire the capability to perform TEG, however, pharmacists should expect to see more research on its use.

References

1. Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, Dunn AS, Kunz R. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST. 2012;141(2 Suppl):e326S-50S.

2. Abdelfattah K, Cripps MW. Thromboelastography and rotational thromboelastometry use in trauma. Int J Surg. 2015;S1743-9191(15)01223-6.