Reducing AB plasma utilisation through the AB plasma appropriateness index.

OBJECTIVES: We hypothesised that there was inappropriate group AB plasma used in our hospital, identifiable by a novel key quality indicator (KQI) and mitigable through massive transfusion protocol (MTP) modification. BACKGROUND: Group AB plasma is a scarce resource strained by increasing usage worldwide when used as universal donor plasma in non-group AB patients. To reduce inappropriate use and to promote benchmarking to the best practice, we developed the AB plasma appropriateness index (ABAI). ABAI is the ratio of AB plasma transfused to group AB or unknown blood group patients to all AB plasma utilised, where values closer to 1 are better. METHODS: Data collected included AB plasma disposition by blood group, indications for transfusion, total blood utilisation, patient clinical characteristics and outcomes. ABAI during a 12-month period was retrospectively assessed, which led to implementation of pre-thawed group A plasma instead of group AB plasma for trauma patients starting in July 2017. RESULTS: The ABAI retrospectively showed inappropriate use in non-group AB patients in our hospital, the majority used to avoid expiry after thaw. When comparing 1-year pre- and post-implementation periods, ABAI improved from 0·464 to 0·900 (P < 0·0001). After exclusion of therapeutic plasma exchange, ABAI still improved (0·486-0·720, P < 0·0001). No differences in the length of stay or mortality associated in 32 patients receiving group A plasma for emergency release were observed. CONCLUSION: The ABAI is a novel KQI to indicate inappropriate AB plasma usage for quality improvement. This led to thawed A plasma use for MTPs, reducing inappropriate AB plasma usage.

Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.

Propagation of venous thrombi or rethrombosis after coronary thrombolytic therapy can occur despite heparin administration. To explore potential mechanisms, we set out to determine whether clot-bound thrombin is relatively protected from inhibition by heparin-antithrombin III but susceptible to inactivation by antithrombin III-independent inhibitors. Using plasma fibrinopeptide A (FPA) levels as an index of thrombin activity, we compared the ability of thrombin inhibitors to block FPA release mediated by fluid-phase thrombin with their activity against the clot-bound enzyme. Incubation of thrombin with citrated plasma results in concentration-dependent FPA generation, which reaches a plateau within minutes. In contrast, there is progressive FPA generation when fibrin clots are incubated with citrated plasma. Heparin, hirudin, hirudin dodecapeptide (hirugen), and D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK) produce concentration-dependent inhibition of FPA release mediated by fluid-phase thrombin. However, heparin is much less effective at inhibiting thrombin bound to fibrin because a 20-fold higher concentration is necessary to block 70% of the activity of the clot-bound enzyme than is required for equivalent inhibition of fluid-phase thrombin (2.0 and 0.1 U/ml, respectively). In contrast, hirugen and PPACK are equally effective inhibitors of fluid- and solid-phase thrombin, while hirudin is only 50% as effective against the clot-bound enzyme. None of the inhibitors displace bound 125I-labeled thrombin from the clot. These studies indicate that (a) clot-bound thrombin is relatively protected from inhibition by heparin, possibly because the heparin binding site on thrombin is inaccessible when the enzyme is bound to fibrin, and (b) clot-bound thrombin is susceptible to inactivation by antithrombin III-independent inhibitors because the sites of their interaction are not masked by thrombin binding to fibrin. For these reasons, antithrombin III-independent inhibitors may be more effective than heparin in certain clinical settings.

Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors.

BACKGROUND: Thrombolytic therapy induces a procoagulant state characterized by elevated plasma levels of fibrinopeptide A (FPA), but the responsible mechanism is uncertain. METHODS AND RESULTS: Washed plasma clots were incubated in citrated plasma in the presence or absence of tissue plasminogen activator (t-PA), and FPA generation was monitored as an index of unopposed thrombin activity. FPA levels are almost twofold higher in the presence of t-PA than in its absence. This primarily reflects the action of thrombin bound to soluble fibrin degradation products because (a) there is progressive FPA generation even after clots are removed from t-PA-containing plasma, and (b) clot lysates produce concentration-dependent FPA generation when incubated in citrated plasma. Using thrombin-agarose affinity chromatography, (DD)E and fragment E but not D-dimer were identified as the thrombin-binding fibrin fragments, indicating that the thrombin-binding site is located within the E domain. Heparin inhibits thrombin bound to fibrin degradation products less effectively than free thrombin. In contrast, D-Phe-Pro-ArgCH2Cl, hirudin and hirugen inhibit free thrombin and thrombin bound to fibrin degradation products equally well. CONCLUSIONS: Thrombin bound to soluble fibrin degradation products is primarily responsible for the increase in FPA levels that occurs when a clot undergoes t-PA-induced lysis. Like clot-bound thrombin, thrombin bound to fibrin derivatives is protected from inhibition by heparin but susceptible to inactivation by direct thrombin inhibitors. These findings help to explain the superiority of direct thrombin inhibitors over heparin as adjuncts to thrombolytic therapy.