Talking Tall Rounds®: Blood Conservation in Cardiac & Vascular Surgery

Podcast Transcript

Announcer:
Welcome to the Talking Tall Rounds Series brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Jennifer Hargrave, DO:
Good morning, everyone. My name is Jen Hargrave, and I just want to start out by offering my thanks for all of those participating this morning in the Blood Conservation During Cardiac and Vascular Surgery Tall Rounds. In just a moment, my co-moderator, Nick Skubas, who is the Chairman of the Department of Cardiothoracic Anesthesia, will be joining us.

Jennifer Hargrave, DO:
But before that, we'd like to set the context with a case, with a complex aortic surgery case in which we use several blood conservation techniques, but before our speakers come, I'd like to invite my chief fellow, Dr. Oscar Tovar Camago, to give just a really brief case introduction for us. So Oscar...

Oscar Tovar Camago, MD:
Good morning. Today, we'll briefly discuss the case with a high incidence of coagulopathy and need for a blood product transfusion, where we use blood conservation techniques to decrease the amounts and need of blood product transfusion.

Oscar Tovar Camago, MD:
In summary, we have a 69-year-old male with aortic dilatation. Of particular interest, his pre-operative labs show an H and H of 14.5 and 43.9, platelets of 177,000, PTT normal, and INR within normal limits. The surgical procedure quite complex includes a total arch repair with frozen elephant trunk anastomosis, two stent B-SAFER procedure, a nominate re-implantation of the distal anastomosis, a valve sparing root replacement. The cross clamp time was a total of 218 minutes, anterior grade cerebral profusion time of 43 minutes, and cardiopulmonary bypass time of 232 minutes. Several blood conservation techniques were utilized, including ANH of a total of 475 milliliters, retrograde autologous prime of the cardiopulmonary bypass circuit, microplegia, cell saver, aminocaproic acid, as well as goal-directed therapy for coagulopathy.

Oscar Tovar Camago, MD:
Here's a brief timeline of the goal-directed management, after separation of cardiopulmonary bypass, as well as administration of the protamine. The autologous blood was returned, a total of 475 milliliters. A TEG, as well as coagulation studies were obtained. Of particular interests, the max amplitude was decreased. The INR was increased, at 1.6, and the fibrinogen was slightly decreased.

Oscar Tovar Camago, MD:
After the coagulation studies, it was determined that one bag of platelets was administered, as well as two bags of FFP. The cell saver was completed afterwards. An ABG was obtained, demonstrating an H and H of 10.2 and 31.6. The patient was then transferred to the CVSU. Upon arrival, the patient was normothermic. New coagulation studies were obtained. Of interest, the INR was elevated at 1.3, fibrinogen was decreased at 129. At this point, it was determined that two bags of FFP and two bags of cryo would be administrated. The next day, the coagulation studies were re-obtained, and the studies were now normalized with no coagulopathy.

Oscar Tovar Camago, MD:
In summary, we have a complex case, with a high incidence of coagulopathy and need for blood product transfusion. This case scenario demonstrates how goal-directed therapy, as well as several blood conservation techniques, can be utilized to optimize and decrease the amount of blood products transfused. Thank you.

Mohamed Abdalla, MD:
A few weeks ago, the Society of Thoracic Surgeons, the STS, together with the Society of Cardiac Anesthesiologists, SCA, in collaboration with the American Society of Extracorporeal Technology and the Society for Advancement of Blood Management, issued the most recent guidelines on blood conservation and patient blood management in cardiac surgery. For the pre-operative interventions, assessment of anemia, determining its etiology and treatment in more cardiac surgery patients is recommended, as well as implementation of standardized transfusion protocols.

Mohamed Abdalla, MD:
Along the same lines of treating a pre-operative anemia is a short course of erythropoietin and iron supplementation pre-operatively in patients who refuse blood transfusion is recommended, as in our Jehovah's Witness patient group. Treatment of asymptomatic anemia and asymptomatic thrombocytopenia with transfusion is actually not recommended. The previous guidelines were generally when they addressed the anti-platelet medications, but these guidelines are more specific when to stop and which drug with a Class A recommendation.

Mohamed Abdalla, MD:
Pre-operative anticoagulants with non-vitamin K oral anticoagulants is a new addition to the guidelines this year, where a reversal of the non-vitamin K oral anticoagulant in emergency cardiac surgery patients with specific antidote is recommended. I think that Andexanet, although it's a great drug, but the cost might be a limiting factor. At the same level of recommendation is, if the antidote is not available, anti-thrombin concentrate is recommended.

Mohamed Abdalla, MD:
What about the intra-operative interventions? The routine use of antifibrinolytic agents is showing up, again, in this guidelines, as the previous one, with Class 1 recommendation a strong level of evidence to decrease bleeding and transfusion in cardiac surgery.

Mohamed Abdalla, MD:
What is new is the recommendation to ... it's a reasonable choice to use tranexamic acid to reduce bleeding in off-pump CABG surgery. Moving to the blood products and derivatives, the era of using fresh frozen plasma to treat heparin resistance should be something from the past. And it is showing again as in the previous guidelines, using anti-thrombin three concentrate for heparin resistance is Class 1 recommendation with a strong level of evidence.

Mohamed Abdalla, MD:
Anti-thrombin concentrate is reasonable to consider over fresh frozen plasma as a first-line therapy, in certain situations. Where there is refractive oculopathy in patients, for example, in the right ventricular failure, cannot handle the burden of the therapeutic volume of FFP. It is not recommended to prophylactically infuse fresh frozen plasma in absence of coagulopathy in cardiac surgery.

Mohamed Abdalla, MD:
I'm not going to discuss the perfusion intervention because Pat Grady is going to talk about that in details, but I want to highlight the importance of acute normovolemic hemodilution, or ANH, is reasonable to reduce bleeding and transfusion in cardiac surgery in selected patients.

Mohamed Abdalla, MD:
Moving to the post-operative fluid management, albumin is a reasonable choice to provide intravascular volume replacement. Meanwhile, hydroxyethyl starch is not recommended. Transfusion algorithms, they are core in the patient blood management and blood conservation in cardiac surgery, and it seems that the debate of restrictive versus liberal transfusion is settling, where restrictive red blood cell transfusion strategy is recommended in preference to liberal. This decreases the allergenic red blood cell transfusion without increasing morbidity and mortality.

Mohamed Abdalla, MD:
Another pillar of blood preservation in cardiac surgery will direct the transfusion algorithms utilizing point-of-care testing, precisely viscoelastic testing. Transfusing red blood cells for hemoglobin more than 10 grams per deciliter is not recommended. A comprehensive multi-modal blood conservation program led by a multi-disciplinary team should be part of any patient blood management to decrease the utilization of our blood resources, at the same time, decrease the risk of bleeding. Thank you.

Stephanie Lombardi, BCCCP, PharmD:
For this portion, I will describe the factor concentrates and prothrombin complex concentrates, or PCCs, available and review their efficacy in managing perioperative coagulopathy. Factor concentrates dependent on the specific product are currently FDA indicated for the treatment of hemophilia, congenital factor deficiencies, and emergency oral anticoagulant reversal. Their use has been described in coagulopathy and bleeding related to cardiac surgery, though it's used as off label for this indication.

Stephanie Lombardi, BCCCP, PharmD:
The baseline of therapy has traditionally been FFP, though PCC offers advantages, including rapid preparation and lower infectious risks and lower infusion volume. As Dr. Abdalla mentioned, the recent peri-operative blood management guidelines do note PCC as a first line option in some refractory cases for coagulopathy related to cardiac surgery and recombinant factor 7A is also noted as an option to consider. Factor concentrates after repleting the vitamin K dependent coagulation factors specific to the product, thus activating the coagulation cascade to promote the generation of thrombin and subsequently fibrin.

Stephanie Lombardi, BCCCP, PharmD:
I'd like to point out the half-life of some of these factor concentrates or coagulation factors, and note that factor seven has a very short half-life of six hours or less, and factor two has a much longer half-life, as these can impact the duration of hemostatic effect of these factor concentrates.

Stephanie Lombardi, BCCCP, PharmD:
In terms of the coagulation, or the factor concentrates, we have several options, and here, I will highlight those that have been most studied in perioperative coagulopathy. Inactive PCCs can be categorized into four or three factor PCCs, based on the presence or absence of factor seven. Anti-inhibitor coagulant complex is the available activated PCC product, and looking at these different PCCs, with the balance of coagulation factors, and anti-coagulants, inactive four factor PCC is thought to be safest, from a thromboembolic risk perspective.

Stephanie Lombardi, BCCCP, PharmD:
These inactive and activated PCC products are human derived from donor plasma. Whereas the single factor concentrate available for a perioperative coagulopathy recombinant coagulation factor 7A is derived from animal species. And this product, with its repletion of simply factor seven, which has a short half-life of six hours or less, is thought to have a lower duration of hemostatic effect.

Stephanie Lombardi, BCCCP, PharmD:
The efficacy in cardiac surgery for factor concentrates is minimal and primarily based on retrospective data. First looking at studies of inactive PCCs compared to FFP, there has been a meta analysis and a recent randomized pilot study comparing inactive PCCs to FFP, as well as several small retrospective studies that mirror these same effects and results, which have shown that PCCs are associated with decreases in transfusion requirements and bleeding severity. Compared to FFP, PCCs have not been shown to increase the risk of thromboembolic events or mortality.

Stephanie Lombardi, BCCCP, PharmD:
There is very little evidence regarding activated PCCs in perioperative coagulopathy, in which the few small retrospective studies do show decreases in transfusion requirements in re-exploration for bleed, though with the risk of thromboembolic events.

Stephanie Lombardi, BCCCP, PharmD:
Recombinant factor 7A has been studied in perioperative coagulopathy in cardiac surgery patients with a variety of data and studied at a wide variety of dosing strategies. These studies primarily show decreases in transfusion requirements and lab evidence of coagulopathy, though mortality data is highly variable and conflicting, with some reports up to 40% mortality. Additionally, recombinant factor 7A is associated with the greatest amount of thromboembolic events, with reports up to 24%. Among all of these factor concentrates, thromboembolic events are increased and more likely to occur with repeated dosing of the factor concentrate.

Stephanie Lombardi, BCCCP, PharmD:
There are additional single factor concentrates that are currently available, though their evidence for use in cardiac surgery is limited, or minimal, or non-existent. However, with the future of the potential for future studies or point of care testing, these could be options down the pipeline.

Stephanie Lombardi, BCCCP, PharmD:
Overall, large prospective studies for factor concentrate use in cardiac surgery related coagulopathy and bleeding is very minimal, and we are waiting for these prospective studies. However, current evidence does suggest that factor concentrates appear to have favorable transfusion requirements and bleeding outcomes in coagulopathy, in particular, pointing towards inactive four factor PCCs when balancing the transfusion requirements and thromboembolic risks.

Stephanie Lombardi, BCCCP, PharmD:
And overall, it is important to consider the risk of thromboembolic events when using any factor concentrates.

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