Coagulopathy in Trauma Seunghwan Kim, M.D. Dept. of Emergency Medicine College of Medicine, Yonsei University

Objective Normal hemostasis Pathogenesis of coagulopathy in trauma patients Evaluation of coagulopathy Treatment

Coagulopathy Definition Failure of the blood to clot normally in response to tissue injury from trauma, surgery, or routine invasive procedures.

Normal Hemostasis

Coagulopathy

Risk factors for coagulopathy Acidosis (pH < 7.1) Hypothermia (core temp. < 34 ℃ ) Severe injury (ISS > 25) Shock (SBP < 70 mmHg) Cosgriff et al, J Trauma. 1997;42:

Pathogenesis of coagulopathy Hemodilution Hypothermia Consumption of clotting factors Metabolic derangments

The “Bloody Vicious Cycle” Vigorous fluid resuscitation Hemodilution Increased bleeding Recurrent Hypotension

Hemodilution Dilutional thrombocytopenia  m/c of the coagulation abnormalities  35-40% of platelets remain in circulation after replacement of one blood volume Dilution of procoagulant factors  Fibrinogen : most sensitive  Massive transfusion

Hypothermia Bleeding : risk factor of hypothermia Quantitative and qualitative platelet dysfunction Alteration of coagulation enzyme kinetics Disruption of fibrinolytic equilibrium

Platelets Thrombocytopenia  Platelet sequestration in the liver and spleen Reduction of thromboxane B2 Inhibition of platelet aggregation Reversible on rewarming

Coagulation factors Clotting studies  Temperature is an important role  PT is most sensitive Altered enzyme kinetics in the coagulation cascades Increased fibrinolysis

Clotting factor depletion Multiple injury Massive clotting factor activation Uncontrolled activation of the fibrinolytic system

Lung and brain injury Severe pulmonary contusion BBB breakdown after brain injury Release of tissue thromboplastin Intravascular activation of coagulation Vigorous fibrinolysis Profile of DIC develops

Liver injury Site of synthesis for all coagulation factors except factor VIII Severe liver injury  Production of coagulation factors decreased  Massive transfusion, hypothermia…

Metabolic derangements Acidosis d/t hemorrhage shock Decrease coagulation enzyme activity Correlation between coagulation abnormalities and the hypotension duration Hypoperfusion is associated consumptive coagulopathy

Massive Transfusion Replacement of the patient’s entire blood volume within a 24-h period Replacement of 50% of the total blood volume within 3h Transfusion of more than 20 RBC units Need for at least 4 RBC units within 4h with continued major bleeding Blood loss exceeding 150ml/min Need for platelet and plasma replacement

Massive Transfusion Hypothermia  Transfusion of large volumes of cold blood product  Impairs the function of platelets  Potential for hypocalcemia Dilutional thrombocytopenia

Massive Transfusion Acid-Base change  Stored RBCs and whole blood; acidic pH  Sodium citrate Converted to sodium bicarbonate  Net effect : alkalosis  Routine administration of bicarbonate with large transfusion; undesirable

Massive Transfusion Citrate  Decreased levels of ionized calcium  Hypocalcemia Hypotension, narrowed pulse pressure, elevated LVEDP, PAP and CVP, ECG abnormality Factor IV

Evaluation

History Medication  Warfarin, asprin, NSAIDs Known bleeding disorder Bleeding tendency  Bruising tendency  Excessive bleeding during medical procedure  Prolonged menorrhea  Repeated or severe epistaxis

Physical Exam Bruising Joint abnormalities Petechiae, purpura Ecchymosis, Telangiectasia Hepatosplenomegaly Malnutrition

Prothrombin time (PT) Adding thromboplastin, containig TF, phospholipid and calcium to citrate plasma Extrinsic pathway and common pathway Affected by vitamin K-dependent factors INR = log patient PT / log control PT

Partial Thromboplastin Time Adding partial thromboplastin, activating substance and calcium to citrate plasma Intrinsic pathway and common pathway Factor VII is not measured

Platelet Count Quantitative measure of circulating platelets Counts < 50,000/mm 3  Increase bleeding from cut surfaces Counts < 20,000/mm 3  spontaneous bleeding

Bleeding Time Only test that measures platelet function and primary hemostasis Relatively insensitive and nonspecific May not predict surgical bleeding

Thrombin Time Adding thrombin to citrate plasma Time for conversion of fibrinogen to fibrin TT Prolonged  Fibrinogen is deficient or abnormal  Presence of circulating anticoagulant  Excessive fibrinolysis

Fibrinogen As clotting increases the fibrinogen level decreases Low level; consumptive condition  DIC, sepsis, severe traumatic brain injury Acute phase reactant

Thrombelastography (TEG) Analyze various characteristics of clot formation; computer analysis and graphic form data Platelet function Coagulation enzyme activity Fibrinolysis Overall degree of coagulability

Fibrin Split Products (FSPs) Not diagnositic Evidence of a consumptive process such as DIC D-dimer; most closely associated with DIC

Treatment

Prevention Easier than treating it once it develops Keep the patient warm and perfused Transfusion therapy; pay close attention to blood composition  Minimize use of non-blood fluids  RBC, plasma, platelet

Packed RBC Packed RBC 1p  RBCs; 195mL  Suspendig fluid; 155mL (Plasma 35mL) Acidic Citrate Low temperature

Platelet 1U ; increase 10,000/uL 50mL anticoagulated plasma 20 to 24 ℃ storage Low acid and thermal burden

Fresh Frozen Plasma (FFP) 250mL, Plasma 80% 500mg fibrinogen 200U of all of the other coagulation factors

Cryoprecipitate Freezing and thawing FFP Concentrates fibrinogen, vWF, Factor VIII, XIII FFP is the better product

Plasma transfusion Low level of evidence Closed laboratory monitoring of hemostasis Rapid blood loss Single plasma doses; ml/kg Cryoprecipitate; 1-1.5packs/10 kg Consider time to thaw and transfer plasma

Clotting Factor Concentrate Factor VIII  Hemophilia A  Greenmono ® Factor IX  Hemophilia B  Facnyne ®

Recombinant Factor VIIa For hemophilia with inhibitor or factor VII deficiency In large doses requires only fibrinogen, thrombin and platelets to produce clotting “Off label” use in trauma  Reduction in bleeding in several studies NovoSeven ®  Very expensive

Rule of thumb in coagulopathy Prevention Recognize the major mechanism and treat it Recognize the general pace of normal patients Establish treatment goals Steady hand on the blood product spigot

References

Mauricio Lynn et al., Updates in the management of severe coagulopathy in trauma patients, Intensive Care Med, :S241-S247 Ray Armand et al., Treating coagulopathy in trauma patients, Transfusion Medicine Reviews, Vol 17, No3, 2003: pp Paul J. Wojciechowski et al., Coagulopathy in massive transfusion, Int Anesthesiol Clin Fall;43(4):1-20 Deborah M. Stein, Richard P. Dutton, Uses of recombinant factor VIIa in trauma, Curr Opin Cirt Care : Peter Hellstern, Hannelore Haubelt, Indication for plasma in massive transfusion, Thrombosis Research 107 (2002) S19-22 D. Stainsby et al., Management of massive blood loss: a template guideline, Br J Anaesth 2000; 85:487-91