Antithrombin concentrates may benefit cardiopulmonary bypass patients with suspected heparin resistance: A retrospective analysis of real-world data.

Background: Heparin resistance is a common complication of surgical patients requiring anticoagulation, such as those undergoing cardiopulmonary bypass (CPB). Treatments to address heparin resistance include supplementation of antithrombin (AT) or fresh frozen plasma (FFP). This retrospective database analysis compared key outcomes in suspected heparin-resistant patients undergoing CPB treated with AT or FFP. Methods: De-identified United States electronic health records (Cerner Health Facts®) were queried. International Classification of Diseases (ICD-9/10) codes were used to determine CPB procedures and FFP administration. AT administration was identified using medication data, while a combination of lab and medication data examining activated clotting times detected heparin resistance in FFP patients. Adult inpatients (≥18 years old) seen between 2001 and 2018 were included. Differences in mortality, intensive care unit (ICU) length of stay (LOS), and hospital-free days (using a 30-day post-discharge period) were assessed with univariate models as well as adjusted logistic regression models controlling for patient characteristics and Charlson Comorbidity Index (CCI) scores. Results: Of the 502 patients identified, 247 received AT and 255 received FFP. The FFP cohort was associated with a higher CCI compared to the AT cohort (3.3 ± 2.4 vs. 2.3 ± 2.0, P < .001). The AT cohort was associated with a 71% (Odds Ratio [OR]: 0.29, 95% Confidence Interval [CI]: P = .003) and 66% (OR: 0.34, 95% CI: P = .01) reduction in mortality when compared to FFP using univariate and adjusted logistic regression models, respectively. Similarly, use of AT also showed a 22% shorter ICU LOS (P = .02) and 10% more hospital-free days in the 30 days following discharge (P = .004) according to the univariate models, though statistical significance was absent within adjusted models in both ICU LOS (P = .08) and hospital-free days (P = .53). Conclusions: Compared to FFP, AT use suggests a reduction in the odds of mortality in suspected heparin-resistant patients undergoing CPB, though larger prospective studies are necessary to elucidate potential differences in hospital-free days or ICU LOS across treatment modalities.

Novel approaches in management of perioperative coagulopathy.

PURPOSE OF REVIEW: The recent advances in hemostatic monitoring, and discussion of the clinical implications of hemostatic therapies based on different blood components and factor concentrates. RECENT FINDINGS: Implementing suitable laboratory tests and transfusion protocols is highly recommended because the laboratory test guided, protocol-driven transfusion approach reduces blood component utilization, and possibly leads to improved outcomes. Timely assessment of coagulation has been difficult using conventional coagulation tests, but thrombocytopenia, fibrin polymerization defects, and fibrinolysis can be quickly assessed on thromboelastometry. The latter testing can be applied to guide the dosing of fibrinogen and prothrombin complex concentrate, which are selectively used to correct fibrinogen deficiency, and improve thrombin generation in acquired coagulopathy. These therapeutic approaches are novel, and potentially effective in reducing the exposure to allogeneic components (e.g., plasma and platelets) and side-effects of transfusion. Although the accessibility of different therapies among different countries, tranexamic acid is widely available, and is an effective blood conservation measure with a good safety profile in various surgical settings. SUMMARY: Our understanding of perioperative coagulopathy, diagnostic tools, and therapeutic approaches has evolved in recent years. Additional multidisciplinary efforts are required to understand the optimal combinations, cost-effectiveness, and safety profiles of allogeneic components, and available factor concentrates.

Failure of lung isolation by a double-lumen endotracheal tube rescued by the concomitant use of an arndt bronchial blocker under direct visualization.

Failure of a double-lumen endotracheal tube (DLT) to isolate the lung during thoracic surgery can have significant consequences. In this report, we examine an approach for rescuing a malpositioned DLT. A 37F left-sided DLT was inserted and its proper position confirmed. After positioning, repeat confirmation of position and the ability to achieve 1-lung ventilation were performed, but inadequate isolation of the lung being operated on was noted after incision. A 7-Fr Arndt bronchial blocker was positioned through the tracheal lumen of the DLT to obtain 1-lung ventilation. This technique can be used to rescue a malfunctioning DLT without the need for extubating and reintubating the trachea.

An evidence-based approach to medication preparation for the surgical patient at risk for latex allergy: is it time to stop being stopper poppers?

The prevalence of latex allergy is increasing in surgical patient populations. Avoidance of exposure to the allergen is essential to minimizing perioperative complications in patients suspected to be at risk. Natural rubber latex has historically been ubiquitous in medical devices containing rubber. In 1998, the Food and Drug Administration (FDA) began to require the labeling of medical devices made from natural rubber latex; since that time substantial progress has been made in identifying latex-free alternatives. However, the rubber stoppers commonly found in pharmaceutical vial closures are exempt from FDA labeling requirements. Examination of the clinical and basic science literature regarding pharmaceutical vial closures supports limiting the rubber stopper to a single needle puncture as a safer practice, with the caveat that no strategy exists for the complete elimination of risk as long as stoppers made from natural rubber latex are used in pharmaceutical vials intended for human use.

Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass.

BACKGROUND: Antithrombin (AT) levels decrease during cardiopulmonary bypass (CPB), particularly when combined with deep hypothermic circulatory arrest (DHCA). Low AT levels might lead to imbalance of pro- and anticoagulant factors promoting systemic thrombotic events. We hypothesized that low levels of AT might lead to increased in vitro thrombin generation when procoagulant factors are added to the patient's plasma after CPB. METHODS: Blood samples were obtained before heparinization and after separation from CPB from five patients undergoing cardiac surgery with DHCA. AT levels were determined by chromogenic assay and expressed as a percent of normal activity. The balance between procoagulant and anticoagulant elements was manipulated in the patients' plasma by adding normal donor plasma, AT-deficient plasma, or purified AT. The Thrombinoscope system was used to evaluate thrombin generation with and without AT supplementation. RESULTS: AT levels (median, range) were 82.0% (71.0, 109) and 37.0% (34.0, 41.0) of normal before and after separation from CPB, respectively (P < 0.05). Peak thrombin generation (median, range) was 56.6 nM (42.1, 61.0) in plasma after CPB, and it remained at 61.1 nM (54.9, 64.5) when a donor plasma with normal AT (105%) was added. When AT-deficient plasma was added to the patient's plasma, peak thrombin generation (median, range) was increased from 56.6 nM (42.0, 61.0) to 117 nM (95.0, 188) (P < 0.05 versus control). After the addition of purified AT, the peak thrombin generation was reduced to 12.2 nM (9.0, 29.3) (P < 0.05 versus control). CONCLUSION: Plasma AT activity is severely decreased after CPB with DHCA. Our data suggest that the administration of coagulation factor components without AT repletion may lead to excessive thrombin generation, which clinically, may potentially lead to a hypercoagulable state.

Effects of recombinant activated factor VII on thrombin-mediated feedback activation of coagulation.

Thrombin is a key hemostatic enzyme, which propagates its own generation by activating factors V, VIII, and XI. Sustained thrombin generation also activates thrombin-activatable fibrinolysis inhibitor (TAFI), which stabilizes fibrin clot against fibrinolysis. Recombinant activated factor VII (rFVIIa) is considered a novel hemostatic intervention for refractory bleeding, but rebleeding episodes related to fibrinolysis still occur. The present study aimed to investigate the antifibrinolytic effects of rFVIIa in relation to thrombin generation. Using thrombelastography, the effects of rFVIIa on thrombin-activated fibrin formation and on fibrinolysis induced by tissue plasminogen activator were evaluated in various factor-deficient plasma samples. A Thrombinoscope was used to quantitate thrombin generation. Thrombin increased antifibrinolytic activity in a concentration-dependent manner as demonstrated by a longer clot lysis time. In plasma deficient in factors V, VIII, IX, X, or XI, clot lysis occurred early (< 20 min), and rFVIIa addition had minimal effect, except for improved antifibrinolytic effect in factor-XI-deficient plasma. A normal clot lysis time was observed in factor-XIII-deficient or dual antithrombin/factor-VIII-deficient plasma. Inhibition of TAFI increased the rate of fibrinolysis. Thrombin generation was delayed or decreased in single factor-deficient plasma except for factor XIII deficiency. After rFVIIa addition, the peak thrombin generation reached over 100 nmol/l in factor-XI-deficient plasma, but not in plasma deficient in factors V, VIII, IX, or X. Thrombin generation and subsequent activation of TAFI were important for clot stability. We conclude that rFVIIa therapy does not compensate for increased susceptibility to fibrinolysis due to lack of factor(s) necessary for the formation of tenase and prothrombinase.