scholarly journals Pharmacologic tools to reduce bleeding in surgery

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 517-521 ◽  
Author(s):  
Sam Schulman
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Decision Algorithm ◽  
Increased Risk

AbstractStrategies to reduce blood loss and the need for transfusions in surgery include enhancement of coagulation, inhibition of fibrinolysis, and an improved decision algorithm for transfusion based on bedside monitoring of global hemostasis. The synthetic antifibrinolytic drug tranexamic acid has emerged as an effective alternative in this respect for orthopedic and cardiac surgery. Although it seems less effective than aprotinin, it has not been associated with the increased risk of mortality of the latter. Thromboelastography to monitor the global hemostatic capacity and to guide the appropriate use of blood components in cardiac surgery is also effective in reducing the need for transfusion. Patients on antithrombotic drug therapy may need reversal before surgery to avoid excessive blood loss, or intraoperatively in cases of unexpected bleeding. Available options are protamine for unfractionated or low-molecular-weight heparin, recombinant activated factor VII for fondaparinux, prothrombin complex concentrate for vitamin K antagonists and possibly for oral factor Xa inhibitors, dialysis and possibly activated prothrombin complex concentrate for oral thrombin inhibitors, desmopressin for aspirin and possibly for thienopyridines, and platelet transfusions for the latter.

Bleeding after cardiac surgery

2006 ◽  
Vol 26 (S 02) ◽  
pp. S76-S86
Author(s):  
C. Spies ◽  
H. Grubitzsch ◽  
H. Schönfeld ◽  
M. Sander ◽  
Th. Volk ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Factor Vii ◽  
Coagulation System ◽  
Severe Bleeding ◽  
International Studies ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Increased Risk ◽  
Heart Lung Machine

SummaryCardiac surgery carries the risk of significant blood loss requiring the transfusion of blood products. In addition to such blood loss, international studies have shown that severe bleeding necessitating re-operation occurs in 3–5% of patients. Morbidity and mortality are significantly increased, so effective and safe haemostatic measures will decisively improve outcome of patients.Recombinant activated factor VII (rFVIIa) has been approved for the treatment of patients with inhibitor haemophilia, as well as with Glanzmann’s thrombasthenia and factor VII deficiency. Many publications have appeared in the last few years which report the successful and reliable use of rFVIIa for the treatment of refractory bleeding after cardiac surgery. This review presents the pathophysiological changes in the coagulation system which occur when a heart-lung machine is used and which have been blamed for an increased risk of bleeding in patients who have undergone cardiac surgery. Published experience with rFVIIa in paediatric and adult cardiac surgery is presented and discussed critically with regard to the efficacy and safety of its use.

Reversal of Novel Anticoagulants in Emergent Surgery and Trauma: A Comprehensive Review and Proposed Management Algorithm

2019 ◽  
Vol 24 (38) ◽  
pp. 4540-4553 ◽  
Author(s):  
Leonidas Palaiodimos ◽  
Jeremy Miles ◽  
Damianos G. Kokkinidis ◽  
Christos Barkolias ◽  
Anil K. Jonnalagadda ◽  
...  
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Antibody Fragment ◽  
Thrombin Inhibitors ◽  
Factor Vii ◽  
Current Evidence ◽  
Factor X ◽  
Recombinant Activated Factor Vii ◽  
Reversal Agents ◽  
Emergent Surgery

Non-vitamin K oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, are increasingly used for thromboembolism prevention. Contrary to older anticoagulants, such as coumadin, when antidotes existed and were broadly used in cases of emergent surgery and bleeding, antidotes for NOACs have not been developed until recently. Moreover, the monitoring of NOAC’s anticoagulant effect varies across different hospital settings and the absence of a single test that can accurately predict the degree of anticoagulation achieved increases the uncertainty. These uncertainties often result in management dilemmas for clinicians when patients who are on NOACs need a reversal of anticoagulation. Until recently, available antidotes for NOACs included only prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII and the less optimal fresh frozen plasma (FFP). Recently though, novel antidotes for NOACs have been developed, including idarucizumab, which is a monoclonal antibody fragment that binds dabigatran, and andexanet alfa, a modified decoy form of the activated factor X (FXa) that binds FXa inhibitors and AT III. Another option, ciraparantag, which is a small molecule that binds to heparin, thrombin inhibitors and FXa inhibitors, is still in phase I development. In this review, we summarize the current evidence and present the available bypassing and novel reversal agents. Finally, we propose an algorithm for the management of patients who take NOACs and present to the emergency department with either trauma and active bleeding or need for emergent surgery.

A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding With Cardiac Surgery

2021 ◽  
pp. 088506662098444
Author(s):  
Alyson Katz ◽  
Tania Ahuja ◽  
Serena Arnouk ◽  
Tyler C. Lewis ◽  
Kassandra Marsh ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Prothrombin Complex Concentrate ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Dose Requirement ◽  
Recombinant Activated Factor Vii ◽  
Packed Red Blood Cells ◽  
Activated Factor Vii ◽  
Fresh Frozen ◽  
Chest Tube Output

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates

2013 ◽  
Vol 110 (07) ◽  
pp. 162-172 ◽  
Author(s):  
András Gruber ◽  
Hanna Tinel ◽  
Ulla Marzec ◽  
Ulf Buetehorn ◽  
Anja Buchmueller ◽  
...  
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Factor Vii ◽  
High Dose ◽  
Factor Xa Inhibitor ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Haemostatic Agents ◽  
Life Threatening ◽  
Anaesthetised Rats

SummaryRivaroxaban is an oral, direct factor Xa inhibitor for the management of thromboembolic disorders. Despite its short half-life, the ability to reverse rivaroxaban anticoagulation could be beneficial in life-threatening emergencies. The potential of prothrombin complex concentrate (PCC; Beriplex®), activated PCC (aPCC; FEIBA®) or recombinant activated factor VII (rFVIIa; NovoSeven®) to reverse rivaroxaban in rats and baboons was investigated. Anaesthetised rats pre-treated with intravenous rivaroxaban (2 mg/kg) received intravenous rFVIIa (100/400 μg/kg), PCC (25/50 U/kg) or aPCC (50/100 U/kg) after initiation of bleeding. Clotting times and bleeding times (BTs) were recorded. Rivaroxaban was administered as an intravenous 0.6 mg/kg bolus followed by continuous 0.6 mg/kg/hour infusion in baboons. Animals received intravenous aPCC 50 U/kg (2 U/kg/minute) or rFVIIa 210 μg/kg. BT and clotting parameters were measured. In rats pre-treated with high-dose rivaroxaban, PCC 50 U/kg, aPCC 100 U/kg and rFVIIa 400 μg/kg significantly reduced BT vs rivaroxaban alone (5.4 ± 1.4-fold to 1.5 ± 0.4-fold [p<0.05]; 3.0 ± 0.4-fold to 1.4 ± 0.1-fold [p<0.001]; and 3.5 ± 0.7-fold to 1.7 ± 0.2-fold [p<0.01] vs baseline, respectively). In baboons pre-infused with rivaroxaban and then given aPCC, BT increased by 2.0 ± 0.2-fold and aPCC returned BT to baseline for the duration of its infusion. rFVIIa reduced BT from 2.5 ± 0.3-fold over baseline to 1.7 ± 0.3-fold over baseline. Prolongation of prothrombin time was reduced by PCC, aPCC and rFVIIa in both species. Rivaroxaban reduced thrombin-antithrombin levels; application of PCC and aPCC, but not rFVIIa, increased these levels. In conclusion, PCC, aPCC or rFVIIa have the potential to reverse the anticoagulant and anti-haemostatic effects of rivaroxaban.

scholarly journals Evaluation of Prothrombin Complex Concentrate and Recombinant Activated Factor VII to Reverse Rivaroxaban in a Rabbit Model

2012 ◽  
Vol 116 (1) ◽  
pp. 94-102 ◽  
Author(s):  
Anne Godier ◽  
Anastasia Miclot ◽  
Bernard Le Bonniec ◽  
Marion Durand ◽  
Anne-Marie Fischer ◽  
...  
Keyword(s):  
Blood Loss ◽  
Thrombin Generation ◽  
Prothrombin Complex Concentrate ◽  
Bleeding Time ◽  
Rabbit Model ◽  
Factor Vii ◽  
Clotting Time ◽  
Recombinant Activated Factor Vii ◽  
Cyclic Flow ◽  
Activated Factor Vii

Background As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis. Methods First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint. Results Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P &lt; 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions. Conclusion rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.

Old and new anticoagulants

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Clotting Factor ◽  
Direct Thrombin Inhibitors ◽  
Self Monitoring ◽  
New Anticoagulants ◽  
Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

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