The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Abstract

Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management ('theranostic' approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient's safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration.

Keywords: Algorithms; Bleeding management; Health care costs; Impedance aggregometry; Patient blood management; Thromboelastometry.

Fig. 1.

ROTEM trace (‘temogram’) displaying the clinically most important parameters and their informative value. FDPs: fibrin (ogen) split products. Courtesy of Klaus Görlinger, Germany.

Fig. 2.

Characteristic ROTEM traces. The diagnostic performance is increased by test combinations, e.g., EXTEM and FIBTEM, EXTEM and APTEM, or INTEM and HEPTEM. CT: coagulation time, A5: amplitude of clot firmness 5 min after CT, A10: amplitude of clot firmness 10 min after CT, MCF: maximum clot firmness, ML: maximum lysis during runtime, LI60: lysis index 60 min after CT, TXA: tranexamic acid (or other antifibrinolytic drug), FXIII: coagulation factor XIII, GPIIbIIIa-R: GPIIbIIIa-receptor, CFT: clot formation time, CPB: cardiopulmonary bypass, HLE: heparin-like effect, OLT: orthotopic liver transplantation, 4F-PCC: four factor prothrombin complex concentrate, EX: EXTEM, FIB: FIBTEM, HEP: HEPTEM, IN: INTEM. Courtesy of Klaus Görlinger, Germany.

Fig. 3.

Evidence-based algorithms for ROTEM (A5)-guided bleeding management in (A) cardiovascular surgery and (B) liver transplantation. Algorithm footnotes: ¹Timing of ROTEM-analysis during orthotopic liver transplantation (OLT): Baseline; re-check after 60 min or in case of bleeding during pre-anhepatic phase; 5–10 min after cava clamping (early anhepatic phase); 30–45 mm after cava clamping (late anhepatic phase); 5–10 min after reperfusion; 30–45 min after reperfusion; skin closure; and always in case of diffuse bleeding as well as 10–15 min after a specific hemostatic intervention. ²Check basic conditions: Temp. > 35℃; pH > 7.3; Ca_i²⁺ > 1 mmol/L; Hb ≥ 7 g/dl. ³Antifibrinolytic therapy [105,107]: EACA can be used instead of TXA (based on local practice). CT_FIB > 600 s represents a flat-line in FIBTEM. Only pre-anhepatic hyperfibrinolysis is associated with increased mortality in OLT [103]; hyperfibrinolysis at/after reperfusion without diffuse bleeding may be self-limiting; re-check ROTEM analysis after ML reached 15% and consider avoidance of TXA treatment. ⁴Fibrinogen dose calculation (stepwise approach; see Table 2): Fibrinogen dose (g) = targeted increase in A5_FIB (mm) × body weight (kg) / 160. Correction factor (140–160 mm kg/g) depends on the actual plasma volume. 10 U Cryoprecipitate ≈ 2 g Fibrinogen concentrate. ⁵Platelet concentrate transfusion: Cave: Platelet transfusion is associated with increased mortality in liver transplantation [123]! Consider compensation by increased A5_FIB ≥ 12 mm. Cardiovascular surgery: Check platelet function with ROTEM platelet (ADPTEM and TRAPTEM) or Multiplate after weaning from CPB and heparin reversal with protamine: A5_EX 23–30 mm or ADPTEM ≤ 35 Ohm∙min: 1 pooled or apheresis platelet concentrate. A5_EX 15–22 mm or (ADPTEM ≤ 35 Ohm∙min and TRAPTEM ≤ 45 Ohm∙min): 2 platelet concentrates. A5_EX < 15 mm: 2 platelet concentrates + fibrinogen substitution. ⁶If 4-factor prothrombin-complex-concentrate (4F-PCC) is not available: 10–15 ml FFP /kg bw or 45 (−90) µg rFVIIa /kg bw (if patient is normothermic and pH > 7.3, Ca_i²⁺ > 1 mmol/L, A5_EX ≥ 30 mm, and A5_FIB ≥ 9 mm but FFP is not effective to decrease CT_EX ≤ 80 s and CT_HEP ≤ 280 s). ⁷Anti-thrombin (AT) substitution: Consider AT substitution in patients with an increased risk of thrombosis (e.g., primary biliary cirrhosis, Budd-Chiari-Syndrome, portal vein thrombosis, malignancies) and/ or known pre-existing severe AT deficiency. ⁸Protamine: Endogenous heparin effect after liver graft reperfusion usually is self-limiting and does not require reversal by protamine. However, consider protamine administration in severe bleeding. ⁹Simultaneous interventions: Maximal three interventions at the same time (in first analysis and severe bleeding). Maximal two interventions at the same time (in second analysis and moderate to severe bleeding). Only one intervention at the same time (in second or later analysis and mild to moderate bleeding). A5_EX: amplitude of clot firmness 5 min after coagulation time in EXTEM, CT_FIB: coagulation time in FIBTEM (CT_FIB > 600 s reflects a flat-line in FIBTEM), ML: maximum lysis (within 1 h run time), ACT: activated clotting time, CT_IN: coagulation time in INTEM, CT_HEP: coagulation time in HEPTEM, bw: body weight, A5_FIB: amplitude of clot firmness 5 min after CT in FIBTEM, CT_EX: coagulation time in EXTEM, PCC: prothrombin complex concentrate, FFP: fresh frozen plasma, LI60: Lysis Index (residual clot firmness in % of MCF) 60 min after CT, LI30: Lysis Index (residual clot firmness in % of MCF) 30 min after CT, IU: international units, AT: anti-thrombin, Ca_i²⁺: ionized Calcium concentration, EACA: epsilon-aminocaproic acid, TXA: tranexamic acid, CPB: cardiopulmonary bypass, rFVIIa: activated recombinant factor VII. Courtesy of Klaus Görlinger, Germany.

Fig. 4.

Evidence-based algorithms for ROTEM (A5)-guided bleeding management in (A) trauma/orthopedic surgery and (B) obstetrics/postpartum hemorrhage. Algorithm footnotes: ¹Check basic conditions: Temp. > 35℃; pH > 7.3; Ca_i²⁺ > 1 mmol/L; Hb ≥ 7 g/dl. ²Antifibrinolytic therapy [105,142-146,153,157,195]: Prophylactic administration of TXA can be given within 3 h after trauma or delivery [142-144,195]. Continuous infusion of TXA can be performed in trauma [142-144]. CT_FIB > 600 s represents a flat-line in FIBTEM. EACA can be used instead of TXA (based on local practice). ³Fibrinogen dose calculation (stepwise approach; see Table 2): Fibrinogen dose (g) = targeted increase in A5_FIB (mm) × body weight (kg)/ 160. Correction factor (140–160 mm kg/g) depends on the actual plasma volume. 10 U Cryoprecipitate ≈ 2 g Fibrinogen concentrate. ⁴Platelet concentrate transfusion: Check platelet function with ROTEM platelet (ADPTEM and TRAPTEM) or Multiplate, if available [168-169]. Cave: Platelet transfusion might not improve platelet function in TIC [170]. Consider compensation by increased A5_FIB ≥ 12 mm. Consider TXA (25 mg/kg) and/or desmopressin (DDAVP; 0.3 µg/kg) in patients with dual antiplatelet therapy and/or ADPTEM < 30 Ω∙min. Expected increase per pooled/apheresis PC per 80 kg: 8–10 mm in A5_EX. A5_EX 28–35 mm or ADPTEM < 40 Ω∙min: 1 pooled or apheresis platelet concentrate. A5_EX 20–28 mm or (ADPTEM < 40 Ω∙min and TRAPTEM < 50 Ω∙min): 2 pooled or apheresis platelet concentrates. A5_EX < 20 mm: 2 platelet concentrates + fibrinogen substitution (≥ 4 g). ⁵If 4-factor prothrombin-complex-concentrate (4F-PCC) is not available: 10–15 ml FFP /kg bw or 45–90 µg rFVIIa /kg bw (if patient is normothermic and pH > 7.3, and Ca_i²⁺ > 1 mmol/L, and A5_EX ≥ 35 mm, and A5_FIB ≥ 9 mm but FFP is not effective to decrease CT_EX ≤ 80 s and CT_HEP ≤ 240 s). Consider acquired hemophilia A in early severe bleeding, EXTEM and FIBTEM are normal but CT_IN and CT_HEP are significantly prolonged (see Fig. 6). Therapy: rFVIIa. ⁶Protamine: Endogenous HLE might occur in severe trauma and shock. Hemodynamic stabilization is the most important therapy. However, protamine administration might be considered in severe bleeding. ⁷Simultaneous interventions: Maximal three interventions at the same time (in first analysis and severe bleeding). Maximal two interventions at the same time (in second analysis and moderate to severe bleeding). Only one intervention at the same time (in second or later analysis and mild to moderate bleeding). ISS: injury severity score, TASH: trauma associated sever hemorrhage, A5_EX: amplitude of clot firmness 5 min after coagulation time (CT) in EXTEM, CT_FIB: CT in FIBTEM (CT_FIB > 600 s reflects a flatline in FIBTEM), ML: maximum lysis (within 1 h run time), A5_FIB: amplitude of clot firmness 5 min after CT in FIBTEM, bw: body weight, CT_EX: CT in EXTEM, 4F-PCC: four factor prothrombin complex concentrate, IU: international units, FFP: fresh frozen plasma, CT_IN: CT in INTEM, CT_HEP: CT in HEPTEM, PPH: postpartum hemorrhage, TXA: tranexamic acid, rFVIIa: activated recombinant factor VII, Ca_i²⁺: ionized Calcium concentration, EACA: epsilon-aminocaproic acid, TIC: trauma-induced coagulopathy, HLE: heparin-like effect. Courtesy of Klaus Görlinger, Germany.

Fig. 5.

A case of ROTEM-guided bleeding management in postpartum hemorrhage. The first ROTEM was performed after PPH activation of the anesthesia team. The first ROTEM showed already a decreased FIBTAM A5 (4 mm) and a late hyperfibrinolysis in FIBTEM (ML 23%). Unfortunately, this has not been treated at this time and coagulopathy and bleeding progressed within the next hour. Due to the delay in treatment, the second ROTEM showed a fulminant hyperfibrinolysis and a flat-line in FIBTEM. Accordingly, 2 g tranexamic acid and 4 g fibrinogen concentrate have been administered (calculated increase in A5_FIB, 8 mm) within 20 min after the second ROTEM analysis and the effect has been checked with the third ROTEM analysis 8 min later. Here, the measured increase in A5_FIB was 2 mm below the calculated increase due to the ongoing bleeding. The prolonged EXTEM CT in the second ROTEM (due to the lack of fibrinogen) normalized in the third ROTEM (borderline results with CT_EX 78 s and CT_FIB 85 s). EXTEM and FIBTEM clot firmness (A5) improved but were still too low and associated with ongoing bleeding. Therefore, further 4 g fibrinogen concentrate, 2 pooled platelet concentrates, and 1500 IU 4F-PCC have been administered in the second ROTEM-guided intervention. This intervention stopped the bleeding and the fourth ROTEM analysis showed a normal temogram for a pregnant woman. The time between the second and fourth ROTEM analysis—including the two ROTEM-guided interventions—was 69 min and overall 6 U RBC and no FFP have been transfused to the patient. No TRALI, TACO, or other complications occurred, and the patient could be extubated after surgery and discharged from the ICU the next morning. PPH: postpartum hemorrhage, A5: amplitude of clot firmness 5 min after CT, A10: amplitude of clot firmness 10 min after CT, ML: maximum lysis during runtime, CT: coagulation time, CFT: clot formation time, MCF: maximum clot firmness, 4F-PCC: four factor prothrombin complex concentrate, RBC: red blood cells, FFP: fresh frozen plasma, TRALI: transfusion-related acute lung injury, TACO: transfusion-associated circulatory overload. Courtesy of Klaus Görlinger, Germany

Fig. 6.

ROTEM pattern of acquired hemophilia A with inhibitors to FVIII. Characteristic for acquired hemophilia, this ROTEM shows a significantly prolonged INTEM and HEPTEM CT (460 s and 555 s, respectively) but short CTs in EXTEM and FIBTEM (53 s and 45 s, respectively) since the extrinsic and common pathway are not affected by this coagulopathy. The appropriate treatment is rFVIIa (recombinant activated factor VII) or activated PCC (FEIBA, Factor Eight Inhibitor Bypassing Activity). ST: start time, RT: run time, CT: coagulation time, CFT: clot formation time, α: alpha angle in °, A5: amplitude of clot firmness 5 min after CT, A10: amplitude of clot firmness 10 min after CT, MCF: maximum clot firmness, ML: maximum lysis during runtime. Courtesy of Klaus Görlinger, Germany.