Reduced Requirement for Prothrombin Complex Concentrate for the Restoration of Thrombin Generation in Plasma From Liver Transplant Recipients

Abuelkasem, Ezeldeen; Hasan, Shaheer; Mazzeffi, Michael; Planinsic, Raymond M.; Sakai, Tetsuro; Tanaka, Kenichi A.

doi:10.1213/ane.0000000000002106

Cited by 44 publications

(41 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One large case series has described the use of PCC and/or fibrinogen in 156 patients (out of a cohort of 266) following liver transplantation; no significant difference was observed in thrombotic, thromboembolic, or ischemic adverse events between patients who received PCC and/or fibrinogen and those who did not . An ex vivo study of PCC conducted using blood samples from liver transplant recipients showed that PCC was more effective than FFP in increasing thrombin generation . Similarly, in a study testing the effects of in vitro addition of hemostatic agents using thrombin generation tests, FFP and rFVIIa only modestly increased thrombin generation in patients with compensated and acutely decompensated cirrhosis, whereas PCC increased thrombin generation 2‐fold to 4‐fold in these patients and approximately 2‐fold in healthy individuals .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, guidelines advocate the use of PCCs to reverse the effects of vitamin K antagonists over FFP because they are concentrated, ensure consistent correction, and reduce the risk of fluid overload . Because vitamin K–dependent clotting factors are also decreased in liver disease, studies have suggested a potential role for PCCs in patients with coagulopathy related to liver disease . PCCs in this scenario have the same advantages over FFP, particularly in actively bleeding patients .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

et al. 2019

View full text Add to dashboard Cite

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large‐volume transfusion. This retrospective, single‐center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16‐29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Here, CT EX with a cut-off of 75 s is superior to predict bleeding in this patient population and CT EX -guidance can reduce fresh frozen plasma (FFP) transfusion and PCC administration significantly [31,97,[124][125][126][127][128][129]. This helps to avoid overtreatment and thromboembolic events [92,97,[125][126][127][128][129][130]. FFP is not effective in increasing thrombin generation in patients with cirrhosis but is associated with a high risk of TACO and portal hypertension [92,97,116,126,130].…”

Section: Vol 72 No 4 August 2019mentioning

confidence: 99%

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

Görlinger

Pérez-Ferrer

Dirkmann

et al. 2019

Korean J Anesthesiol

176

138

View full text Add to dashboard Cite

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. 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.

show abstract

“…31 A study in liver transplant patients with prolonged INR confirmed that PCC can effectively restore thrombin generation, but noted that the required doses of PCC are lower than for warfarin reversal, likely as a result of slow thrombin inhibition. 32 A recent study confirmed the efficacy of PCC in patients with liver disease, without an excess of thrombotic events, and also observed lower dosing with PCC compared to anticoagulant reversal. 33 Additionally, this study did not evaluate interactions with other hemostatic modalities, such as desmopressin and antifibrinolytics, and therefore may not fully reflect the multifaceted treatments that patients with thrombocytopenia may receive in clinical practice.…”

Section: Discussionmentioning

confidence: 85%

“…For example, a clinical trial to evaluate the use of the thrombopoietin‐receptor agonist eltrombopag to increase platelet count in patients with thrombocytopenia and chronic liver disease was terminated due to an increased incidence of portal vein thrombosis in the treatment group . A study in liver transplant patients with prolonged INR confirmed that PCC can effectively restore thrombin generation, but noted that the required doses of PCC are lower than for warfarin reversal, likely as a result of slow thrombin inhibition . A recent study confirmed the efficacy of PCC in patients with liver disease, without an excess of thrombotic events, and also observed lower dosing with PCC compared to anticoagulant reversal .…”

Section: Discussionmentioning

confidence: 99%

Impaired platelet‐dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro

Chowdary

Hamid

Slatter

et al. 2020

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet‐dependent TG over and above that of simple replacement therapy. Objective To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia. Methods TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20‐300 × 109/L) were spiked with PCCs (25%‐150% increase in plasma PCC levels). Results PCCs and platelets significantly increased TG in a dose‐dependent manner in vitro. Two‐way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG. Conclusions Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation.

show abstract

Reduced Requirement for Prothrombin Complex Concentrate for the Restoration of Thrombin Generation in Plasma From Liver Transplant Recipients

Abstract: Reduced TG in LT can be more effectively restored by using PCC rather than plasma. The required doses of PCC for LT patients seem to be lower than warfarin reversal due to slow thrombin inhibition.

Cited by 44 publications

References 40 publications

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

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

Impaired platelet‐dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro

Contact Info

Product

Resources

About