Presented as part of the Department of Cardiovascular Surgery Grand Rounds on October 21, 2020, by Mehdi Oloomi, MD, at the end of this video, the viewer should be able to:
It's a pleasure to welcome many Lumi today to give this some talk. He's going to speak about management of bleeding post op and in postoperative heart surgery. And Mehdi is a is a you know, one of our directors in the ICU. And he's also a master of the uh not only at the bedside but of literature. He's one of one of my absolutely top ranked reviewers for the Journal of American College of Cardiology. So he has a very critical perspective. Um that's that's evidence base, which is something I really like I learned on one of our trips. Mehdi, I believe you called it. What was it, the illuminator? I I've learned to respect his knowledge of the of the evidence, not just, you know, his sort of clinical instinct. So this should be a fun talk and he's getting going to catch us up about bleeding after heart surgery. So many thanks for doing this. Thank you very much. Doctor Adams. Good morning everybody Today. I have a plan to overview bleeding and cardiac surgery patients in four parts reviewing the hemo surfaces during the cardiac surgery evolution of our understanding about the most cases in the last two decades, our current coagulation tests are optimal and at the end, hopefully about the transfusion management after open heart surgery. As you see, the diagram leading in cardiac surgery, patient is all about the balance between the pro coagulants and anticoagulants factor and bleeding happened when the balance of the scale tilt to the right on the anti coagulation side, right side of the diagram that you see. Yeah, There are four major factors that might be considered during the operation. One, the circuit of the heart lung machine needs to be prime With 1- 1.5 L of the Crystal Lloyd. In addition, some patients who had received A and H. NH involved removal of the whole blood and substitution with the chris, salary, crime NG and NH caused human dilution. Therefore lower concentration of the coagulation factors and the lower platelets. Second blood is interfacing with the non in detail real surface. It's critical to anti coagulate the blood. So we use a massive dosage of the happening Average around 400 international units per kg. Third We know any trauma in that escape from the physiology. Anti coagulation system can activate physiology fiber analytic system during cardiopulmonary bypass production of the trump being increased By 10 to 15 times. Interestingly not only fiber releases system can get activated during the on palm but also during the off farm operation ford increasing number of the patient Nowadays who are on the newer type of the P two Y 2 inhibitor or do axe may need a cardiac surgery emergency or urgently All these four major factor is working as a polka as an anti coagulation uh limp on the pro coagulant side of the scale, we have interfacing of the blood with the non industrial surface. There is also massive release of the tissue factor secondary to the pre cardiac to me and associated to she injury that can activate a coagulation system. Finally, we use cell saver, which have some of the pro coagulant factors such as tissue factor, on the other hand, has a lower level of the coagulation factor because does not filter and the lower level numbers of the platelets. Therefore self serve air has both pro coagulant and human delusional effect. At the end we reverse the effect of the happening with the programming. So when we deal with the patient post operation all the time, we have to consider this major eight factors that is happening every day on each patient. You know. Coagulation normally start through the tissue factor as you see on this one uh this diagram through the and the classic extrinsic pathway which eventually ended up with the formation of the trump being and which trump being convert fiber agent for the firing. It used to call it extrinsic pathway. But nowadays as we know, we do not have an intrinsic factor separately in vivo Trump being and the trumpet by itself and the tissue factor complex with factor seven. They amplify clot formation through the element of the extensive path. Faith as you see on the diagram. So we need a tissue factor Plus the factor seven activated and the trumpet which both sides are going to be amplified the platform ation. As you've seen in viva coagulation cascade, there is no more presence of the factor two of anymore. Coagulation usually take place on the false phillipe surface of the activated platelet membrane B. Shot in this diagram, cooperation required a calcium which we do not see it has it You can see in order to have a clot formation, it's essential to have a fiber energy. No wonder we call it factor one two fibers and convert to the fire brain. We need a factor to pro trump. Being too uh get activated to the activated factor to which we call it trumpet. And finally we need this factor tree which we call a tissue factor. Although we have more than 13 different factors which one of them they are not exist and one of them is the calcium. But this trip factors is important in all coagulation cascade fiber now john try ambient and the tissue factor. Okay these diagrams show the critical role of the trump being on the platelets in the italian all generation of the firing and activating protein C. I know it's a busy diagram and we know nowadays lots of about the structural of the each cascade of the proteins but if you see on the lower part of the diagram trumping is going to work on the uh huh. Um On the platelet membranes on the upper part on the right hand side is action of the trump being to activated protein C. Trump. Being directly can work on the fiber information and we know the trumpian is working on the editorial cells so it's important to recognize that trump being is the most important molecule in the coagulation cascade is the most potent molecule and it is a small amount of it. It can make all the blood in the circulation to clot to feed in a few minutes. Yeah our body has an anti trump being that neutralized trumpian and other activation coagulation factor and the right diagram is c. The boat factor 10 a. And the Trump being is going to be uh neutralized by anti trump in hampering, increase the rate of this trumpian pro trump complex formation. By the factor of several thousands. The dosage of the heparin has gradually increased from 250 units per kg to now around 400 units per kg During the cardiopulmonary bypass. And even sometimes up to the 600 units per cage in the United States, it's generally accepted that the city of the 4 20 to 4 82nd correlated with the heparin level of the 3 to 5 unit per militar. Activating cotton's time as you may know, is a point of care test. You take a sample of the whole blood and activated by an activators such as fast full a bit resulting the platform ation which is measured by the magnet or optic basically is a highly sensitive and the poor specific test huma dilution and hypothermia can affect the accuracy of the significantly as you may ever. We use the hep con system in Sinai. The head can use an individualized hampering those response care to calculate the patient happening bowlers, those to achieve a targeted ACDC and in the world individualized heparin. Uh those responses calculated by mixing the patient's blood bit zero 1.5 and 2.5 unit per military dosage of the heparin. The head can then calculate the baseline A ct from the control of zero and two additional a ct values From the happening. Those are 1.5 and 2.5. The head can h. M. S. Use the three a ct value and the patient estimated blood volume to determine the heparin bolus toes. Yeah. Nowadays in the cartilage of the A. C. T. We have a different concentration of the pro to me so we can indirectly calculate the happening level. This is important for the pro timing dosage adjustment. Access proto mean can have an adverse reaction including multiple hated prosperity's and the bleeding. Keep in your mind the patient leave the operating room in Sinai theoretically the happening level of zero. They have but not in the reality definitely there is some advantage to the head con. But there are disadvantaged such as actually mentioned in the reference three of this paper which are recommended for the resident to look at it. What are those con for the hep con system? Inaccurate estimation of the patient blood loss, lack of the facility of the major happening concentration, inheritance, inaccuracy of the device and the difference in in vivo and ex feeble happening activities. Mhm. Mhm. So what what is the happening re bond which is important? Heparin everybody is the reactivation of the heparin effect. That a cure five minutes to five hours after the neutralization. With the pro time in sulfite. The heparin effect likely awkward because of the ability of the large molecule of the heparin sequestering in fat Esther and the plasma protein with the eventual re apprehended in the blood at some time after the programming neutralization interestingly about 10-15 of the patients receiving usual happening those for the cardio primary bypass will have a detectable heparin level two hours after the approach. I mean reversal. There is no value for the or activated protect plus in time or a PTT. For the diagnosis of the Heparin. Re bond heparin anti 10 A. Is considered the gold standard. As of now If we send the heparin anti 10 a. And the first post operative blood sample. And we value and the value is more than a .2 is a diagnostic for the heparin respond. And then additional dosage of the programming can be given. Mhm. Yeah. Yeah. In 2018 society of the thoracic surgeon and two other society of cardiovascular and physiologists and american society of the extracorporeal technology came with a clinical practice guidelines. After more than six decades of the cardiopulmonary bypass, we finally have a manuscript with evidence and the practice recommendation which I highly recommended everyone, particularly the residents and fellows to read. It's about the 10 pages. And as you see on the slide in regard to the heparin re bond. The recommendation is because of the risk of the happened rebounding patient requiring high dose of the heparin And with prolonged cardiopulmonary bypass time Load those programming infusion 25 milligram per hour for as long as six hours after the end of the cardio. Primary bypass may consider as a part of the multi modality blood conversation conservation program. Level of the evidence. Is C. What it means the high dose of the heparin when we use it more than a for 100 units per kg. And what it means by the prolonged cardio primary bypass time when the bypass time more than three hours. Mhm. It's necessarily to mention in people who have a morbid obesity or higher or those who have a higher Bmi the chance of the head primary bond is higher. Yeah. Since we are on the subject of the happening and happening respond, few points must be mentioned about the pitfall of the activated um PTT PTT Develop in 90 53 in the University of the North Carolina. This is the reason the color of the back entertainer tube top is a Carolina blue, Believe it or not, pity, developed in 1935. The activated PTT access the intrinsic and the common pathway. As you see on the diagram, basically lab at the region that content to forcefully pete this fossil epic drive from the animal or plant and consequently activator. First of all, the composition of the false Philip, it varies in the different lab and a different batch of the same lab. Secondly, the technical, you know, the amount of the blood that we send in the lab is very important. We know the limits of this test in cardiac surgery. Glenn and his colleague did a prospective study of the 900 cardiac surgery patients looking at the function of the series of the clotting tests, including PT PTT trump in time. The best multi variant model constructed could only explain 12 of the observed variation in post operative blood loss. That was for a long time. We know the validity of the PTT. And the PT PTT is only accurate to the heparin level up to the one unit per militar. After that it's not an especially accurate test. P. T. And A PTT show growth abnormality of the intrinsic and extrinsic pathway. At the same time, we know in cardiac surgery, no relationship has been found between the reduction in the coagulation factor concentration and the severity of the post operative bleeding. Following cardiac surgery, it used to be the exception of the fiber energy. So it means if the fiber energy level is low, the chance of the bleeding is I, but hopefully at the end of their slide, I showed. The result of the replace trial was a negative circulating residual happen is commonly present following surgery and is not correlated the day A PTT. I personally do not create the isolated A PTT in post op ICU patient except they have a clinical bleeding. Mhm. Let's look at the other major component of the homeostasis, which is platelets. First. Platelet adhesion happen mainly by exposure to the collision of the sub and to tell you all um surface And its bond is facilitated by the one Gillibrand factor. After adhesion, platelet become activated with a series of the enzyme such as From Pakistan, a two trump being epinephrine And more than nine other enzyme. Finally, platelet become aggregated mainly through the Like a protein to be and three a. And the Fiber Nation. If you see activation of the platelet is very important and the configuration of this cell particle has been changed significantly after cardio formally by fast most of the patients are trauma side of panic and this from a psycho pena is more than just delusional effect. It assumed that the trump being activated platelets and result in their adhesion to the circuit with amon aside and the neutrophils interestingly postponed platelet or semi active. Although post bypass patients or trauma side of panic and their plated are dysfunctional. There is no consensus as to what extent this phenomenon contribute to blood loss. Post operatively. Yeah Griffin and his colleague, they look at more than 1300 patients who had open heart surgery. Around 26 Was Trauma said to panic less than 75,000. The paper published in this year. It means one out of the four patients post open heart surgery. They are trump said appendix. Less than 75 1000 interestingly in their study, they find those who are from beside the panic. They have a higher more ability such as ai infection and stroke. In addition, we know the flow saitama tree of the platelet after cardio, primary bypass shows series of the receptors such as like a protein to be three A. Like a protein four. And the CD 35 has been decreased significantly. So post open heart surgery, platelet both, the number is low and they are dysfunctional. Mm. When trump cited pena is present present, functional essay would be abnormal because most of the functional essay is depend on the absolute number of the platelets. Moreover, some studies has been shown it take period of the six days to platelet regain their function. Keep in your mind Performing the platelet function on a patient with the platelet count of less than 100,000 is not advocated. As I said, When the number of the platelet is less than 100. This functional ass A. Is going to be abnormal with the increased usage of the anti platelet, chance of the post operative bleeding. Re exploration and transfusion is higher if they are not stopped before the surgery. The recommendation is hold to hold the surgery for 5-7 days. In urgent cases with the expense of one person increase in the list of the my card er uh infection. When we transfused platelets, it should be individualized based on the type of the surgery such as the patient had a coronary bypass surgery. That the patient has a main stain Which type of the P. two Y. to uh block our patient was on it. Did the patient get the recently card your cat? And finally, what is the absolute content of the platelet function absolute contact the platelets. It's one thing actually I can say in the prentice's because 25% of the patient there are non responsive to non responded to P. Two Y two blocker. And some work has shown that the plant late function can correct within three days of stopping this medication. We can measure the function of the plate pre operatively either by the tech platelet mapping If they'd be less than 20 inhibition Or multiple. eight if you area under the curve, be more than 20 For a. d. p. on day three and find which patient fit for the surgery. to reduce that time of 5-7 days to holding these on P. Two Y. Two blocker. That is one of the recommendations that they can use in conclusion functional essay of the platelet post operatively immediate does not have that much of the meaning Pre operatively ba can stratify which patient can get surgery. And finally This is a paper published in 2017. And the aim of this study was to see the effect of the single ill inter operative transfusion of the platelet on bleeding and the odd adverse outcome. They look at almost 24,000 patients And identify 170 patients and 500 patient as a reference group. What they find the group who received the platelet. They had less blood loss but they have a more radioactive medication usage. Pro longer ventilation and I see you and the blood product post operatively play. The transfusion should be like other modality which should be considered on a case by case basis. one size does not fit all no optimal tests we have available now for the platelet function except the total number of the platelets. Mhm. Let's free to get in normal homeostasis. Any trauma being that escaped there um escapes activated plasma urgent to the plasma. As you see under this diagram. And this plan's main change phi brain to the phi brain degraded product F. B. P. S. And D. Di MERS. During the cardio. Primary bypass production of the trump being Increase more than 10 to 15 times in cardiac surgery. Did I murder increases and is correlated with the increased post operative bleeding. Hyper fiber license. Falling cardiopulmonary bypass As a cause of the bleeding is taught to icon for 6-8 of those patients who black nowadays we use it TX say that inhibit production of the plasma in from plasminogen is a the block uh the conversion of the plasma to plasma nation and decrease bleeding in the cardiac surgery. Yeah. Inter operative administration of the anti fiber analytic agents such as T. X. A. Is a class one a recommendation in cardiac surgery As the last SCS guideline. However, we have a limited efficacy and safety data on the T. X. A. And with the respect to the patient subgroups. Because the profile of the medication roughly between 7-13 of the time T. X. A. can create a seizure and the patient and it's not a very safe profile. This medication hat if you look at it, a study was published recently, they look at the 300 more than I'm sorry, more than 3000 patients who go under elective cardiac surgery and the major D. Diamond prior to the surgery and the pro and the before pro timing administration. They find those group of the patients who get the TX at the fixed dosage, the timer decrease in Group of the patient who were on pump and off one bypass valve surgery and Elvis. But the level increasing aortic and the those patients who had a transplant, they concluded the assessment of the fire analytic status may have the potential to facilitate those adjusted anti fiber early therapy in future. But I want to conclude that although we give everybody T. X. A. T. X. A. It might have a traumatic event event if they get an access those and it is a profile of the medication is not clear. It's this a study create the idea probably should be again on case by case individualized the dosage of the T. X. A. That we wanted to give. Yeah Trumbo a lasto graphic. The test was first described by heart heart in 1948. The first reported clinical application of the tag tests occurred during the Vietnam war in an attempt to guide transfusion of the blood complete in injured soldier. So basically it's nothing that much knew about this technique although recently has been popularized in tech. The whole blood and the region is incubated in a heated cop and a pin is introducing the sample to measure the fiscal elastic property of the forming clots. The tech, the cop oscillate basically. And in the rotan rotational trump. Last program, the pin is rotate in rotten the fiscal, assess the measured by the optic and teg measured by the torch and wire. They are form the impotence graph in the dynamic fashion as you see it on the diagram, the lower diagram and basically the information is get you show it in the diagram as our It means initiated of the cloth platt formation. We have a maximum maximum amplitude which is the highest strength of the clot formation. And this clot by the matter of the time, fiber license is a start An arbitrary they pick up 30 minutes time and they call it fiber license in rotten. We can measure four channel in the pirate depend on the re agent. We add major different part of the coagulation cascade. If you add the tissue factor in one of the channel, so it means we measure extrinsic pathway in vivo, in vitro, it looks like a pt. If we add the foster lipid, then we measured there intrinsic pathway looks like a PTT. So the latter we call it in time. And then when we measured the extrinsic pathway we call it X time. We can measure the clot formation by blocking the action of the platelet when we add the another region. And this one we can say the dynamic or functional essay of the fiber energy information which we call it, you know, Philip them Most of the functional asset of the 5th um has been done in the European country. And because the measurement of the fifth time can happen in 10 minutes, we can measure the helped um it means we add the hair primaries to their cup and then we look at the coagulation without the persons of the happening. And finally we can do that take place. That mapping is a method for the testing the ability of the platelet to participate in the cloud formation with or without contribution of the anti platelet drugs. But as I said, primarily previously, if you say is 80 of the 100,000 platelets they are functional. The whole sentences contradicted because Vnd platelet count is around 100,000 and platelet count is the the plate that they are dysfunctional because absolute number is more important is that some center they use a eco TEM is very sensitive and we use a direct trump being inhibitor. And basically we put at the re agent to the cop with like a train which is blocking the trumpet. The question is what the utility of the Rotem or tech which the verdict is not out. I usually ask cardiac anesthesia fellow to give us a talk regardless of the tag in the I. C. U. And if they talk about the pros of it, I talk about the cons if you talk about the they talk about the cons, I talk about the pros. It has a lots of the technical personally actually I used to take for the period of the two years before I come to the Sinai is a lot of technical issue that this should be considered. For example the bed should be um table should be as straight february, a little bit felt that this pin might be rotated abnormally. Or when you do the tech test, if somebody, let's say be near to the machine and a little bit touch the table or the table or touch the table or the machine, the result of the tech would be abnormal. So then the more I actually I use it, uh I see a contradict er uh report it means rotate is abnormal, but the patient is not bleeding or vice versa. Yes. Yeah. All right. So let's see what, how we can. Now we understand the major principle of the what's going on during the cardiac surgery, How we can manage it on those patients who bleed. Uh fresh frozen plasma. Keeping your mind plasma is not a good source for the fiber nation. To increase the fiber asian level by one g per liter, We need 33 cm per kg of the F F. B. Equal to the two liter of the plasma. For the 70 kg patient In Cochran. Review objective was to evaluate the risk benefit ratio of the FFB transfusion in cardiac surgery for the treatment of the bleeding patient or for prophylactic against the bleeding. As far as the leading patient, the conclusion of Cochran review was in cardiac surgery. Further adequately poverty study are required to assess whether the large reduction in the P. T. Translate into the clinical benefit and as to the prevention randomized control trial for the safety and efficacy of the prophylactic transfusion of the FFT for cardiac surgery is insufficient. Mhm. Second thing is a crier. Precipitated cry is opting by tying FFB at 1 to 6 C. Then centralization has happened and the re suspending the precipitate protein in plasma and rephrasing re freezing it. Cryo is a multi donor required inventory according to the blood type and required time for time and pulling before the transfusion. It usually takes time to release one Bag of the Cryo. The standard dosage has between 8 to 10 units of the tall FFb in Mancina is about 4 to 5 units of the FFT and it has a mont Sinai we have Iran 800 to a grand maximum of the fiber region level. It has a factor eight And factor 13. Cryo is a multi donor product with no antiviral processing. Most of the european country except England. They don't have it. And the guidelines suggest that the cryo precipitate should not be used to control bleeding related to the low fiber energy in level. If a specific factor concentration are available. And finally, platelets are generally administrated on platelet count, one unit increased roughly about 50,000. Most of the platelet we use are the pool platelet is from the different donor for a patient with the ITP which rather recently we should ask for the single donor platelet pro trump being complex concentration or the PCC. It obtained from the cryo. It has either factor to 9:10 Or 27,910. It is standardized according to the factor nine concentration. It has a happening and proteins C. N. S. Therefore for the patient that we want to treat it for the H. I. T. We have to remember some of this product has a happening, It has a 25 times concentration of those factors in the blood we currently use for urgent reversal of the vitamin K. And to be honest, keep in your mind we have a five different products which we have a three of them in Mount Sinai and we should know which product we're using it. For example the Baxter mcafee bia has a high level of the factor seven. And in the bible in is another product that we have. It has a low amount of the factor seven. If the patient has a fiber nation level of the 1.5 is for trump being complex concentration does not work. So as I said Factor one is a fiber energy and fire engine has to be present to the PCC to be able to work K. Central as a Trump traumatic complication of about one person. If they use the dosage of the 15 mikes per kg. Limited data is are available depend on the product and the institution PCC has the role. Most of it is a case report is a three paper actually recently published. All the authors of the second order is a dr levy that they use it on the limited number of the patient. And as of right now is a prophecy trial is going on is a single center open level randomized pilot trial in England that will assess whether it is feasible to perform a large trial in the future that will compare FFB with the PCC in cardiac surgery patients. There is the result of the randomized controlled trial in Netherland for liver patient was promising but limited number of the patient was in this study the last time I was talking about the coagulation, we said we are waiting for the results of this study. The results of the study for the liver patient is out in the Netherlands. Mhm. But the total number of the patient they use it is less than 30 five version is the highest concentration factor in the blood among all the other factors it used tooting believe level of more than one g per liter is sufficient. Post operatively current geiler recommended high 11 in post cardiac surgery patient. More than 1.5 g 150 mg per deciliter. We do measure for hibernation arrival today. I see you here in Sinai. By class method. In class medal we add a trombone and the clot formation time is recorded. Gi spectroscopic analyzed might falsely elevated with the stars solution. So we do not use a starch solution or like a head discharge but might have an abnormal result. Class method. As I said in point of the care or in the road. Um test maximum amplitude is correlated with the fiber nation. Several study has been published. She got the role of the fibers and cardiac surgery. Some of the important as follows Pre operative vibration concentration. Less than three are reported to increase transfusion requirement for the coronary bypass surgery. Two in prospect of observational study of the close to 2000 patient fiber nation level on the ICU admission were lower in bleeding patient and it was a predictor of the bleeding. In a small prospective study, fiber version reduced transfusion compared to the placebo to unit vs 13 respect respectively. Multiple studies show reduction of the allergenic blood transfusion in ascending aorta replacement. Few years back, I give a talk. We were waiting and they replace ah the study was going on which was a randomized evaluation of the fiber energon versus placebo in complex cardiovascular surgery. So the result is out unfortunately, like many other modality. When we did a randomized trial, human fiber login was associated with increased allergenic blood product transfusion. An unexpected finding contrary to the prayer. Previous studies, they wanted to put the blame on this randomized because the protocol was complicated or the patient, they had adequate number of the adequate level of the fire engine, but the result of these randomized study was negative as far as the role of the fiber energy. Briefly, I talked about the two other factors that we have available. One is a factor uh seven or recombinant factor seven. Uh It's we use it as an off label. Um It has a significant usage of the significant incident on the incident of the Trumbo's is I personally a long time ago use it in twice and on the beginning Of the 2004. I remember vividly on the patient, bleeding was finally, patient has a thrombosis And usually we use it as a last resort. Factor 13 concentration um was promising in 2006 by but safety and efficacy study did not show any benefit in transfusion reduction. The only usage of the factor 13 in one limited study, if the level of the factor less than a 20-30 of the normal can be used in instead of the anti fiber analytic therapy, which reduce the amount of the transfusion. So she came with that diagram that that's the way I usually look at the patient when they come to the issue. If somebody has a clinical bleeding, begin coagulation tests and usually we wanted to be activated to get the results of the test fast back. If the patient has been getting high dose of the protest, how does that happen in the operating room If they are having high BMI Usually I give them protesting if I suspected a heparin respond and the reassessed ability. It is important to mention it and during all this time you're going to keep the patient normal turbo kick and is another factor acceptable range of the hematocrit because an emir beget more bleeding. If the result of the test come back platelet less than a 50,000 cry or less than it or fibers and less than a 200 And the F. F. B. I give it then the iron ore is more than 1.5. That's the back of my mind is going on. Time is the essence gathering all the relevant information such as palm time. Total dosage of the heparin patient, temperature time of the cardiac cat. If the patient received load of the P two Y two has been patient on the dark any bleeding disorder patient has and so forth. Can help to make that decision. And it's important after any um component replacement. We're doing it. We have to re evaluated again from A to Z. It means rechecked the labs and then if the patient has a life threatening hemorrhage, massive transfusion protocol can be I should be activated and might be considered to give a programming complex concentration. I just want to finish my talk. Great uh strategy alone won't win a game or a battle. The wind comes from the basic blocking and tackling. Although I outlined for us a strategy it won't work uh by itself for proper management of the leading cardiac surgery. Every aspect such as blood bank readiness of the surgical team, patient temperature and so forth. Must because must be considered. Thank you.
