EMSS17: Bleeding patients course material

Transcription

1 EMSS17: Bleeding patients course material Introduction During the bleeding patients workshop at the Emergency Medicine Summer School 2017 (EMSS17) you will learn how to assess and treat bleeding patients from a transfusion medicine point of view. This document should provide more than enough knowledge regarding blood and transfusions during EMSS17. It is not necessary for you to know everything, but this should give you an overview of the topic even if you only remember parts of it. The important things are on the pocket guide that we will use during the summer school. We will cover how treatment varies with different severities of bleeding (uncontrollable bleeding, moderate bleeding, and anaemia). We will briefly discuss different blood products and essential medications, how to monitor the coagulation (the ability of the blood to clot), and how to avoid and treat coagulopathies (decreased clotting ability of the blood). This information is non-exhaustive, and we focus on what is clinically most relevant. Additional information must be sought elsewhere. Blood components, types, coagulation and essential medications Blood components A blood donation consists of ~500 mls of whole blood. Whole blood is separated into the three different components, because most patients only need a single component, and because the components have different shelf lives. Before separation, leukocytes (white blood cells) are removed from the blood by filtration to avoid them from attacking the recipient s tissues. Whole blood is separated into the following three components: 1. Red blood cells (RBCs): ~45% of whole blood. RBCs transports the oxygen necessary for survival and the CO 2 produced by cellular metabolism that must be excreted by the lungs. Red blood cells are put in a storage fluid that keeps the cells alive for approximately 1 month. 2. Plasma: ~55% of whole blood. Plasma contains everything in the blood that is not cells. The most important thing in this context is coagulation factors: proteins, that are essential for coagulation. One of these coagulation factors is fibrinogen. Like RBCs, a storage fluid is added to plasma. This fluid contains citrate that removes ionized calcium (Ca 2+ ) from the plasma to prevent it from coagulating in the bag. The plasma is then frozen and fresh frozen plasma (FFP) is usable for ~3 months. 3. Platelets (thrombocytes): ~ 1% of whole blood. Platelets are also essential for coagulation. They are also kept in a storage fluid, and as the percentage of platelets in whole blood is low, platelets from multiple donors (4 donors in emss17.sats-kbh.dk 1

2 Copenhagen) are pooled into 1 unit of platelet concentrate (PC). Platelet concentrates have a shelf life of ~1 week. Coagulation in brief The innermost layer of every blood vessel consists of the endothelium. The endothelium is a single layer of cells that regulate contraction of the blood vessel, facilitates transport of substances from blood to tissue (and vice versa), and most importantly in this context: contains substances that prevent the blood from clotting inside the vessels. Below the endothelium several substances that initiate coagulation are found. When the endothelium or the entire blood vessel (and eventually the surrounding tissues) is damaged, blood comes into contact with subendothelial connective tissue and coagulation is initiated, primarily by the coagulation factors. During coagulation, platelets and coagulation factors bind to the tissue. A chain reaction of coagulation factor reactions happens on top of the platelets (the coagulation cascade), resulting in the formation of thrombin, an enzyme that converts fibrinogen into fibrin. Fibrin cross-links the platelets, and a coagulate (or clot) is formed. Ionized calcium (Ca 2+ ) is necessary for coagulation factor function. After some time the fibrin and the clot is broken down by plasmin. This is called fibrinolysis. Blood types If you are not familiar with the AB0 and Rhesus D blood type systems, further information can be found here: When a patient is bleeding, you should ideally give blood components of the same type as the patient s own. If the blood type is not yet known, we have to draw a blood sample so we can figure it out as soon as possible. In the meantime we can give universal blood consisting of 0 RhD-negative RBCs and thrombocytes and AB RhD-negative FFP. Balanced transfusions and whole blood When a patient is bleeding and loosing whole blood, it can be necessary to replace every component of the blood. We do this by giving RBCs, FFP and PC in a 1:1:1-ratio, similar to that of whole blood. Thus, if platelet concentrates are pooled from 4 donors, 4 units of RBCs, 4 units of FFP and 1 unit of PC (pooled form 4 donors) equals whole blood. We call this a balanced transfusion or a 1:1:1-ratio. Balanced transfusions are NOT as good as the whole blood in our vessels. The storage fluids dilute the blood and some cells/factors are damaged and lost during donation, storage, and transfusion. Consequently, the blood we give a bleeding patient will never be as good as the patient s own, due to lower oxygen carrying capacity and decreased ability to coagulate. Additional medications Besides the three different blood components listed above (RBCs, FFP and PC), there are a few additional medications and a single additional blood product that you should know of: emss17.sats-kbh.dk 2

3 1. Fibrinogen concentrate: Fibrinogen concentrate derived from plasma can be given on its own if necessary. This allows us to give the patient a higher concentration of fibrinogen than what is possible using plasma alone. 2. Cryoprecipitate: This is also a blood product made from plasma. It has a higher concentration of coagulation factors, including fibrinogen, compared with FFP and can be given when we want to administer additional coagulation factors, especially fibrinogen to a patient. 3. Tranexamic acid (TXA): In some diseases and situations, lysis of the clot happens too quickly. Fibrin and clots are broken down too early or before they are fully formed. TXA inhibits plasmin and consequently inhibits fibrinolysis. This can help stop the bleeding. Stop the bleeding! Bleeding can be due to surgical and/or medical causes. Often patients are bleeding due to both surgical and medical causes. Bleeding due to surgical causes will lead to shock that in turn will lead to development of coagulopathy. Surgical/mechanical bleeding control The first step to stop a bleeding is often to apply pressure. This can be done manually and with devices, such as tourniquets ( The pressure stops the bleeding or slows it down so that the coagulation system has a chance. Additionally, surgery is often necessary to stop bleedings. The specific surgery needed varies from situation to situation and we will not go into detail with this during EMSS17. In general, though, if a patient needs surgery to stop the bleeding, the patient should be brought to surgery as fast as possible and unnecessary delays should be avoided! Bleeding control from a transfusion medicine point of view Bleedings can be due to impaired ability of the blood to clot. This is called coagulopathy. Coagulopathies can cause bleeding on their own, but also often aggravate bleedings caused by mechanical/surgical/traumatic reasons. Coagulopathies can develop due to several reasons. During EMSS17 we will focus on: 1) stopping bleedings and swiftly calling for expert help from surgeons where necessary, 2) preventing and treating coagulopathies, and 3) transfusing patients in the most optimal way. Reasons for coagulopathies The following list contains reasons and physiologic derangements that lead to coagulopathies and that should be considered, avoided, and corrected when possible. The list is not exhaustive. 1. Dilution: Bleeding patients lose whole blood RBCs, plasma, and platelets. It is necessary that the patient s blood contains enough RBCs to carry oxygen and enough plasma and platelets to coagulate. Replacing blood losses with fluids (such as saline) will dilute RBCs, platelets, and coagulation factors, leading to impaired coagulation. It is therefore necessary to replace massive whole blood losses with balanced transfusions (1:1:1-ratio) from the early phase. Fluids can be used for smaller, controlled bleedings or in the initial phase until blood emss17.sats-kbh.dk 3

4 arrives, but fluids do not have the ability to coagulate or carry oxygen and will dilute the patient, leading to impaired coagulation. A patient with massive blood loss needs blood, and massively replacing it with fluids will not help the patient. Remember that blood products are already coagulopathic due to the dilution with storage fluids and degeneration of cells and proteins during storage, and fluid will dilute the patient further. 2. Hypothermia: All enzymatic processes in the human body, including those of platelets and coagulation factors, depend on optimal temperatures for optimal function. Consequently, hypothermic patients can have impaired coagulation and should be warmed to > 36 C. 3. Acidosis: All enzymatic processes in the human body have an optimal ph-value at which they function best. Bleeding patients are often acidotic due to shock. During shock, oxygen delivery to tissues is impaired, leading to lactate acidosis and impaired coagulation. Shock should be corrected, and adequate oxygenation and ventilation (to ventilate CO 2 ) should be ensured to prevent acidosis and coagulopathies. 4. Electrolyte disturbances: As ionized calcium (Ca 2+ ) is necessary for coagulation factor function, hypocalcemia will also lead to coagulopathy. FFP contain citrate that binds ionized calcium and prevents plasma from clotting in the bags. Administering large amounts of plasma will lead to the administration of large amounts of citrate. This binds the ionized calcium naturally present in the blood, leading to coagulopathy. Consequently, ionized calcium should be monitored and supplemented to a level of mmol/l during massive transfusions. Additionally, hyperkalemia (elevated potassium in the blood) can lead to coagulopathies and K + should be treated to remain <5 mmol/l. 5. Medical reasons: This includes treatment with anticoagulants and thrombocyte inhibitors. These situations require assistance from a transfusion medicine specialist and will not be covered specifically during EMSS17, but you should know of their existence. Additionally, patients may suffer from genetic diseases impairing coagulation and platelet functions can be impaired for other reasons for example in patients with chronic kidney disease and uremia. Following trauma, cardiac arrest, and other extreme situations the body can develop a coagulopathy in response to the situation. If the patient is bleeding, correcting this coagulopathy is crucial for survival! Less severe trauma can lead to increased clotting (hypercoagulability), moderate trauma can cause decreased clotting capability, and severe trauma can cause decreased clotting capability and hyperfibrinolysis. Damage control surgery is often applied in bleeding patients where bleeding control requires surgery, but patients are coagulopathic, for example due to the above-mentioned reasons. Briefly, bleedings are stopped using pressure and temporary packaging of organs/vessels. When bleeding is under control, the patient is transferred to an intensive care unit and stabilized, followed by definitive surgery after stabilization. During damage control surgery, permissive hypotension is often applied. With permissive hypotension, blood pressure is kept high enough to ensure emss17.sats-kbh.dk 4

5 perfusion, but lower than the normal blood pressure. This slows down blood loss, just like turning down the flow through a water hose or water pipe makes repairing the hole easier. Damage control surgery is accompanied by damage control resuscitation. This concept consists of balanced transfusions and the prevention/treatment of situations leading to coagulopathies. Monitoring coagulation To recognize and treat coagulopathies, we have to monitor the coagulation. You may know of the blood tests International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). These tests were developed to monitor the effect of anticoagulants on coagulations factors. They only monitor coagulation factor activities and are consequently not optimal in the bleeding patient, where we need to monitor the ability of the whole blood to clot. Thrombocyte counts can monitor the amount of thrombocytes, but not their function, and consequently, this test is not ideal in bleeding patients either. Instead the so-called Viscoelastic Hemostatic Assays can be used. One of these tests is called thrombelastography (TEG) (another is called ROTEM they are interchangeable, but reference values differ and during EMSS17 we will focus on TEG). This test monitors the function of whole blood. A small amount of whole blood is added to a rotating cup with a pin inserted. When the blood coagulates, the clot will make the pin start moving with the cup. By monitoring the movements of the pin, the clot strength can be assessed. The machine looks like this: Blood is drawn from the patient in a sample tube with citrate, so ionized calcium is removed in order to prevent the blood from clotting in it. When the blood has been added to the cup, ionized calcium is added manually again. A substance that initiates coagulation (like the subendothelial substances mentioned earlier) is also added to the cup. The blood in the cup is kept at 37 C. emss17.sats-kbh.dk 5

6 The test creates a graph with time (in minutes) on the horizontal axis and amplitude (movement of the pin) on the vertical axis. The following variables are then measured (normal values in parentheses): - R (3-9 minutes): The reaction time, the time until the clot starts forming. This is primarily dependent on coagulation factors. - MA (51-69 mm): The maximum amplitude, the maximum strength of the clot. This is primarily dependent on fibrinogen and thrombocytes. - FF MA (14-27 mm): The functional fibrinogen maximum amplitude. The amount of the MA that is dependent on fibrinogen. This is measured in a separate cup, where a substance that prevents the platelets from contributing to the clot s total strength is added. The functional fibrinogen TEG is thus a separate analysis that can be done at the same time. The TEG tracing (the figure above) looks like the regular TEG tracing, but with smaller maximum amplitude. When the MA is decreased, a decreased FF MA indicates that the patient lacks fibrinogen (or fibrinogen and platelets), however when MA is decreased and FF MA is normal, this indicates that the patient lacks platelets. - Ly30 (0-4%): Percentage of clot lysis 30 minutes after the MA has been reached. Ly30 measures the amount of fibrinolysis, and increased fibrinolysis can be treated with an antibrinolytic: TXA. - Angle (55-78 ): How rapidly the clot is forming (clot kinetics), important for the total strength of the clot. The angle is primarily dependent on fibrinogen. In the algorithm taught at EMSS17, angle is primarily important when Ly30 is increased. Sometimes when a patient is hypercoagulative (clotting too much/too easily), fibrinolysis is increased as well, which can be appropriate. This is called reactive or secondary hyperfibrinolysis, and expert help should be sought before this is corrected with TXA, as the patient can otherwise clot too much leading to problems. You should not focus much on angle for now, only when relevant in the algorithm on the pocket guide (next page). emss17.sats-kbh.dk 6

7 A treatment algorithm according to TEG is provided in the pocket guide (page 2 shown, downloadable at the website): When multiple TEG values are deranged, they should ideally be corrected in the order: Ly30 à R à MA, as mentioned in the pocket guide (see above, including an exception). TEG has some limitations. The most important are: 1. The temperature of the patient has to be measured, as the TEG analysis is always done at 37 C. If the patient is hypothermic the patient can be coagulopathic for this reason and still have a normal TEG. 2. Because calcium is removed by citrate when the blood sample is drawn and then added during the TEG analysis (in order to allow the blood to clot in the cup), TEG cannot detect hypocalcaemia leading to coagulopathy. This has to be measured using other blood tests, i.e. an arterial blood gas. 3. Finally, TEG does not measure the amount of RBCs and the hemoglobin level. This has to be measured using regular blood samples (for example rapidly analyzed arterial blood gas samples). A normal amount of RBCs is necessary for oxygen delivery and to prevent shock that also leads to coagulopathy. emss17.sats-kbh.dk 7

8 Remember, that the hemoglobin (Hb) is a concentration not a total amount! The Hb concentration will not decrease immediately when a patient is actively bleeding whole blood, unless the patient is diluted, but lost RBCs should still be replaced! Examples of TEG profiles in different situations (these are meant to show you different examples, you do not need to memorize them!): Normal TEG All parameters normal Hypocoagulable: Low coagulation factor concentration, anticoagulants, haemophilia: R, angle, MA, Ly30 Hypocoagulable: Thrombocytopenia, thrombocytopathy, platelet inhibitors: R, angle, MA, Ly30 Hyperfibrinolysis: Major traumas, obstetric catastrophes, reperfusion after liver- or vessel surgery or cardiac arrest: R, angle, MA, Ly30 Hypercoagulable with secondary/reactive hyperfibrinolysis for example disseminated intravascular coagulation (DIC) stage 1, a situation where blood clots too easily in the vessels: R, angle, MA, Ly30 Hypocoagulable: Dilution, DIC stage 2 which is a consumption coagulopathy where factors and platelets are used up and coagulation is impaired: R, angle, MA, Ly30 emss17.sats-kbh.dk 8

9 Bleeding different situations The pocket guide presents transfusion strategies for the three different situations mentioned in the beginning (page 1 of the pocket guide, downloadable at the website): 1. Massive, life-threatening bleedings: Massive, life-threatening bleedings are situations where the patient is C-unstable (in shock) or bleeding fast enough to develop circulatory shock rapidly. In situations with massive, life-threatening bleedings, it is important to stop the bleeding. This will require surgery and correct transfusions. You should give balanced transfusions of RBCs, FFP and platelets in a 1:1:1 ratio. Additionally, TXA is often given prophylactically to strengthen clots and avoid or treat the hyperfibrinolysis that can develop in trauma, major obstetric bleedings, major surgery and other situations. Early, prophylactic TXA can save lives! Finally, you should avoid and treat reversible causes of coagulopathy. emss17.sats-kbh.dk 9

10 Results from TEG may not become available fast enough during massive, life-threatening bleedings, but when results arrive, treatment can be adjusted accordingly eventually with the help of a blood banker or transfusion medicine specialist. The priority during this phase is to stop the bleeding and give balanced transfusions! When control over the bleeding increases, go to the next step. 2. Moderate, controllable bleedings: Moderate bleedings are bleedings that require treatment and attention, but where it is easier to keep up with the losses and the patient is not at immediate risk of death. They can develop for different reason, spontaneously or when you gain control over a massive, life-threatening bleeding. During moderate bleedings, you have enough time to transfuse the patient according to the TEG and Hb-measurements. Reversible causes of coagulopathy should still be treated and avoided. 3. No active, apparent bleeding anaemia and deficiencies: When the patient is not actively bleeding, you should be restrictive with transfusions. Blood products are expensive, a limited resource and transfusions carries several risks (see Thus, transfusions should only be given when necessary. Hb-triggers to guide RBC transfusions exist, and these together with an assessment of whether the patient has symptoms of anaemia (lack or RBCs to carry oxygen) should be followed. Abnormal values measured using TEG should not automatically be corrected if the patient is not actively bleeding. FFP, platelets and TXA can be given prophylactically before situations with expected bleedings (for example before surgeries), varying from situation to situation. Guidelines or experts can be consulted when necessary in these nonemergency situations. Final words As written at the beginning, you should not memorize everything in this document. The important things are on the pocket guide, and we will cover the rest during EMSS15. Remember: If you are in doubt, always seek expert help call your blood banker or transfusion medicine specialist! Materials prepared by the EMSS17 Bleeding Patients workshop-team: Granholm A, Nørgaard SK, Thoft L, Chaachouh H, Kristensen CM, Brixen G and Creutzburg A. If you find any errors in this document, do not hesitate to contact us. emss17.sats-kbh.dk 10