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STABILIZING THE CLOT. CAN WE DECREASE MORBIDITY AND MORTALITY IN OUR TRAMATIC PATIENT POPULATION?. Traumatic Hemorrhage Care Over The Years. . Mast Suit Trendelenburg Fluid Resuscitation Cold/Lots Tourniquets. Current Prehospital Care. Tourniquets Patient positioning Direct pressure
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STABILIZING THE CLOT CAN WE DECREASE MORBIDITY AND MORTALITY IN OUR TRAMATIC PATIENT POPULATION?
Traumatic Hemorrhage Care Over The Years. • Mast Suit • Trendelenburg • Fluid Resuscitation Cold/Lots • Tourniquets
Current Prehospital Care • Tourniquets • Patient positioning • Direct pressure • NS fluid resuscitation • Recognition and rapid transport.
WHY IS FLUID A POOR CHOICE? • Dilutes clotting factor • Dissolves clots • Increases arterial and venous pressures • Increased hemoglobin loss • Decreased circulating volume NORMAL SALINE DOES NOT CARRY OXYGEN!
More Pressure More GPM • Same goes for vascular pressures. If you increase the pressure you increase the hemoglobin loss and in the prehospital environment we don’t have any way to fix it.
Belly Bleed • 12 YO Male • Head on TC • Lap Belt Injury • BP 60 pulse 130 belly hard as a rock. • Skins were poor and ALOC • 30-40 min for an airship • H OW DO YOU TREAT HIM?
WHAT ARE THE OPTIONS • BLOOD REPLACEMENT • O-Negative, Packed cells, Platelets • Cost • Availability • Storage • Shelf life • Data • VOLUME EXPANDERS • Some data shows minor benefit • ARTIFICIAL OXYEGEN CARRIERS • Not FDA approved for human use
TRANEXAMIC ACID Instead of dissolving the clot, diluting clotting factors and increasing hemoglobin loss… LET’S STABILIZE AND IMPROVE THE CLOT * WE ARE IN THE BUSINESS OF CLOT MANAGEMENT: STROKE, PE, MI AND NOW BLEEDING CONTROL.
Tranexamic or TXA • Tranexamic Acid or TXA is an anti fibrinolytic that competitively inhibits the activation of plasminogen to plasmin by binding to specific sites of these enzymes that dissolve clots.
BENEFITS • Safe to administer, has been in use for over 40 years • Significant decrease in mortality in traumatic hemorrhage • Cost effective • Easy to store • Easy to administer • Not a blood product (no religious objections) • Well studied, with a significant amount of data • Allows us to maintain Permissive Hypotension
ADVERSE EVENTS • Possible but not proven by any literature. • Pulmonary Embolism • Deep Vein Thrombosis
LITERATURE • CRASH2 • 274 hospitals, 40 countries, 20,000 adult trauma pts. • TXA given less than one hour post injury resulted in a 32% decrease in death due to bleeding. • One to three hours post injury TXA shows a 21% decrease in death due to bleeding. • More than three hours showed a increase in mortality of 30% • No increase in Thromboembolic events with TXA
MATTERS • Military Application of TXA in Trauma Emergency Resuscitation. • 896 combat casualties, Bastion Role 3 Facility in Afghanistan. • 27% decreasein all cause mortality in patients getting at lease one unit of blood. • 50% decrease in mortality in patients receiving 10 or more units of blood. • Increase in DVT and PE probably due to increased injury severity.
THE PROPOSED STUDY • EPAT • Early Prehospital Antifibrinolytic Therapy TXA will be administered in the prehospital setting to trauma patients with associated indices of hemorrhagic shock followed by a second dose of TXA to be administered at ARMC.
INCLUSION CRITERIA • 18 or older • Systolic BP below 90 • Estimated blood loss of 500 cc in the field • Penetrating trauma to head, neck or torso proximal to the elbow or knee. (excluding superficial graze wounds) • Bleeding not controlled by direct pressure or tourniquet • Major amputation of any extremity
EFFICACY OF TXA • The efficacy of TXA shall be assessed via its effect on: • Mortality • Total and types of blood product used • Total estimated blood loss • The occurrence of thromboembolic events
Why Prehospital • The earlier the better! • Both CRASH 2 and MATTERS proved it.
Thanks • ARMC • ICEMA • Dr Neeki • Bernie Horak • Bill Jones
Hemostasis In Traumatic Hemorrhagic Shock The Use Of TXA Michael M. Neeki, DO,MS, FACEP
Goal • Describe the three mechanisms involved in hemostasis • Explain how the extrinsic and intrinsic coagulation pathways lead to the common pathway, and the coagulation factors involved in each • Discuss Products involved in treatingHemorrhagic shock • Tranexamic Acid (TXA), Evidence-based medicine
Three step to achieve Hemostasis • Vascular Spasm • Formation of the Platelet Plug • Coagulation
Vascular Spasm • The smooth muscle in the walls of the vessel contracts dramatically. Has both circular layers; larger vessels also have longitudinal layers. • The circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present, draw the vessel back into the surrounding tissue.
Formation of the Platelet Plug • The platelets begin to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial lining. • This process is assisted by a glycoprotein in the blood plasma called von Willebrand factor, which helps stabilize the growing platelet plug. As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to hemostasis.
Coagulation • The process is sometimes characterized as a cascade, because one event prompts the next as in a multi-level waterfall. • The result is the production of a gelatinous but robust clot made up of a mesh of Fibrin—an insoluble filamentous protein derived from fibrinogen, the plasma protein introduced earlier—in which platelets and blood cells are trapped.
Clotting Factors Involved in Coagulation In the coagulation cascade, chemicals called clotting factors prompt reactions that activate still more coagulation factors. The process is complex, but is initiated along two basic pathways: • The extrinsic pathway, which normally is triggered by trauma. • The intrinsic pathway, which begins in the bloodstream and is triggered by internal damage to the wall of the vessel. • Both of these merge into a third pathway, referred to as the common pathway
Clotting Factors Involved in Coagulation • All three pathways are dependent upon the 12 known clotting factors, including Ca2+ and vitamin K . • Clotting factors are secreted primarily by the liver and the platelets. The liver requires the vitamin K to produce many of them. Vitamin K (along with biotin and folate). • The calcium ion, considered factor IV. The 12 clotting factors are numbered I through XIII according to the order of their discovery.
Transfusion Products • Primary resuscitation approach to minimize trauma-induced coagulopathy. Plasma, red blood cell and platelet ratios of 1:1:1. (6 RBC: 6 FFP: 6 platelet) • activated prothrombin complex concentrate* -Rivaroxaban and Dabigatran - hypothermia and acidosis - combination with TXA • Activated factor VII (rFVIIa; NovoSeven)
Transfusion Products • Vitamin K (Increases Factors II, VII, IX, X, Protein C and S) • Fresh-frozen plasma (indicated when there is multi-factor deficiencies associated with severe bleeding and/or DIC) • Cryoprecipitate (may be indicated if the plasma fibrinogen is less than 1 g/l)
Antifibrinolytics • These agents enhance hemostasis when fibrinolysis contributes to bleeding • Lysine analogs * EACA (e-AminoCaproic acid * TXA ( Tranexamic acid * Aprotinin ( No marking since 2007)
Mechanism of Action • A synthetic derivative of lysine that inhibits fibrinolysis by blocking the lysine binding sites on plasminogen • Inhibits both Plasminogen activation and Plasmin activity thus preventing clot breakdown. • 10x more potent than Aminocaproicacid in vitro.
TXA • Is useful in a wide range of hemorrhagic conditions. • In large, randomized controlled trials, significantly reduced perioperative blood loss compared with placebo in a variety of surgical procedures, including cardiac surgery with or without cardiopulmonary bypass, total hip and knee replacement and prostatectomy, gynecological procedures.
FIBRINOLYSIS Intact fibrin clot Fibrin clot exposed to plasmin
Pharmacokinetics • Absorption – – Onset of action: 5-15 minutes – Duration: 3 hours • Distribution – – Protein binding ~ 3%; primarily to Plasminogen • Metabolism –Only a small fraction of the drug is metabolized (less than 5%). – T1/2: 2-11 hours • Excretion – – Urine (>95% as unchanged drug)
Protein binding • The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen (does not bind serum albumin). • Pass the Blood Brain Barrier • In patients with hereditary angioedema, inhibition of the formation and activity of plasmin by tranexamic acid may prevent attacks of angioedema by decreasing plasmin-induced activation of the first complement protein (C1).
Dosing/Storage • TXA (Cyklokapron) – 1gm in 100cc/NSS given over 10 minutes (loading dose) – Followed by 1gm in 100cc/NSS over 8 hrs • Can be mixed with just about any available solution • Not to be administered in the same line as blood or blood products or in a line used for rFVIIaor Penicillin • Should be stored between 15-30C or 56-86F