Heparin supplement counteracts the prohemostatic effect of prothrombin complex concentrate and factor IX concentrate: An in vitro evaluation

Brinkman, Herm Jan M.; Patiwael, Sanne; Tripathi, Shrijana; Meijers, Joost C. M.

doi:10.1016/j.thromres.2016.01.017

Cited by 7 publications

(22 citation statements)

References 42 publications

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“…Furthermore, the different heparin content of different PCC and aPCC products must be taken into account when interpreting POC results. 53 For instance, the presence of heparin can be unveiled by coupling kaolin-activated TEG or INTEM assay with the specific enzyme that degrades heparin (heparinase); EXTEM assay on the contrary is insensitive to heparin and could therefore underrate the new hemostatic balance reached in anticoagulated patients treated with heparin-containing procoagulants.…”

Section: Discussionmentioning

confidence: 99%

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

Iapichino

Bianchi

Ranucci

et al. 2017

Semin Thromb Hemost

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Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds.

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Section: Discussionmentioning

confidence: 99%

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

Iapichino

Bianchi

Ranucci

et al. 2017

Semin Thromb Hemost

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“…Total protein was determined according to Bradford [71]. Heparin was determined against the 6th international standard for unfractionated heparin [73]. Thrombin generation (CAT method) in normal plasma supplemented with 1 IU/ml PCC was performed as described using a tissue factor concentration of 5 pM [73].…”

Section: Other Plasma Protein Constituentsmentioning

confidence: 99%

“…Heparin was determined against the 6th international standard for unfractionated heparin [73]. Thrombin generation (CAT method) in normal plasma supplemented with 1 IU/ml PCC was performed as described using a tissue factor concentration of 5 pM [73]. ETP values (extrinsic thrombin generation, area under the thrombin generation cure) are expressed as % of those obtained in normal plasma supplemented with saline instead of PCC.…”

Section: Other Plasma Protein Constituentsmentioning

confidence: 99%

“…Several reports have pointed to a potential negative effect of heparin supplement on the procoagulant efficacy of PCC [73,76,[79][80][81]; though all of these are in vitro studies, a clinical effect should not be ruled out. Let us envision a patient on rivaroxaban anticoagulation treated for an emergency bleed with the advised dose of PCC of 50 IU factor IX/kg body weight (bw), infused at a generally practiced flow rate of 2.5 IU factor IX/kg bw per min [82].…”

Section: Heparin and Antithrombin Supplement: Its Influence On Pccs Pmentioning

confidence: 99%

“…It is therefore to be expected that coinfused heparin may only transiently counteract the prohemostatic efficacy of administered clotting factor concentrate. Additional complicating aspect when treating emergency bleeds in patient on rivaroxaban or any other NOAC, is the fact that co-infused heparin supplement will enhance the anticoagulant effect of the NOAC (see Figure 4 and reference [73]). Thus, an inhibitory effect of heparin during and shortly after infusion of heparin-containing PCC should be taken into account, especially when treating emergency bleeds associated with NOAC anticoagulation.…”

Section: Heparin and Antithrombin Supplement: Its Influence On Pccs Pmentioning

confidence: 99%

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Prothrombin Complex Concentrate, a General Antidote for Oral Anticoagulation

Brinkman¹

2016

Anticoagulation Therapy

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Prothrombin complex concentrate (PCC) is used for the rapid reversal of vitamin K antagonist (VKA) anticoagulation. PCC is also applicable in situations requiring rapid reversal of anticoagulation by non-vitamin K antagonist direct thrombin and factor Xa inhibitor oral anticoagulants (NOACs), thereby making PCC a general antidote for oral anticoagulation. In this chapter, the composition of different PCC brands is reviewed and a negative effect of heparin supplement in some products is recognized. Mode of action of anticoagulation reversal by PCC is explained. Dosage and clinical efficacy, two closely related issues, are discussed and based on reviewed data recommendations are given that may prohibit too low PCC dosing, especially in NOAC anticoagulation. Use of unsuitable laboratory assays has raised needless controversy as to the applicability of PCC to reverse anticoagulation by NOACs, in particular dabigatran. In this chapter, various laboratory assays are evaluated for their applicability in monitoring reversal of anticoagulation.

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Reversing direct factor Xa or thrombin inhibitors: Factor V addition to prothrombin complex concentrate is beneficial in vitro

Brinkman

Swieringa

Zuurveld

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Background Prothrombin complex concentrate (PCC) is a human plasma‐derived mixture of partially purified vitamin K‐dependent coagulation factors (VKCF). Current therapeutic indication is treatment and perioperative prophylaxis of bleeding in acquired VKCF deficiency. Off‐label uses include treatment of direct factor Xa‐ or thrombin inhibitor‐associated bleeds, treatment of trauma‐induced coagulopathy, and hemorrhagic complications in patients with liver disease. Objective Considering PCC as a general prohemostatic drug, we argued that its clinical efficacy can benefit from supplementation with coagulation factors that are absent in the current PCC formulation. In this study, we focused on factor V. Methods We mimicked a coagulopathy in vitro by spiking whole blood or derived plasma with the direct oral anticoagulants (DOAC) rivaroxaban or dabigatran. We studied DOAC reversal by PCC and factor V concentrate (FVC) using a thrombin generation assay, thromboelastography, fibrin generation clot lysis test, and microfluidic thrombus formation under flow. Results In DOAC‐treated plasma, PCC increased the amount of thrombin generated. The addition of FVC alone or in combination with PCC caused a partial correction of the thrombin generation lag time and clotting time. In DOAC‐treated whole blood, the combination of PCC and FVC synergistically improved clotting time under static conditions, whereas complete correction of fibrin formation was observed under flow. Clot strength and clot resistance toward tissue plasminogen activator‐induced lysis were both increased with PCC and further enhanced by additional FVC. Conclusion Our in vitro study demonstrates a beneficial effect of the combined use of PCC and FVC in DOAC reversal.

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Heparin supplement counteracts the prohemostatic effect of prothrombin complex concentrate and factor IX concentrate: An in vitro evaluation

Cited by 7 publications

References 42 publications

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art

Prothrombin Complex Concentrate, a General Antidote for Oral Anticoagulation

Reversing direct factor Xa or thrombin inhibitors: Factor V addition to prothrombin complex concentrate is beneficial in vitro

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