Basic Clinician Training Module 3 Basic bleeding profiles

Introduction to bleeding Causes of bleeding Mechanical – vascular injury Pathophysiological – imbalance between the anticoagulant/antithrombotic and prothrombotic forces of the hemostatic system Monitoring hemostasis – finding where the imbalance resides

Monitoring bleeding with the TEG TEG analysis – monitoring hemostatic components and their interactions. Mechanical – Normal TEG parameters Pathophysiological R: enzymatic pathway abnormality Angle (a): fibrinogen deficiency MA: platelet abnormality LY30: fibrinolysis (See Module 6)

Decision Tree Hemorrhage Fibrinolysis Hypercoagulable C.I. > 3.0 EPL > 15% No or Yes LY30 > 7.5% Hemorrhage No C.I. > 3.0 Yes C.I. < 1.0 > 3.0 No R > 10min R < 3min Yes Primary fibrinolysis Secondary fibrinolysis No Yes Low clotting factors Platelet hypercoagulability Fibrinolysis No MA < 55mm Yes MA > 73mm No Yes Low platelet function Enzymatic hypercoagulability Enzymatic & platelet hypercoagulability a < 45º i Yes Hypercoagulable Low fibrinogen level

Mechanical bleeding Characterized by bleeding patient with a normal TEG tracing. Probable cause: Surgical injury to blood vessel with insufficient repair of the blood vessel. Other possible explanations Clot development not confined to injury site – suggests vWF deficiency Presence of platelet inhibitors

Patient status: bleeding Probable cause (3): Vessel injury vWF deficiency Presence of platelet inhibitor

Patient status: bleeding Probable cause  Common treatment: Vessel injury  Suture vWF deficiency  DDAVP Presence of platelet inhibitor  Run Platelet Mapping

Enzymatic pathway abnormalities Characterized by a bleeding patient and a TEG tracing with an abnormally long R value. Factor deficiency may also cause abnormalities in other TEG parameters (angle, MA) Probable causes: Coagulation factor(s) deficiency Coagulation factor dysfunction Presence of anticoagulant (i.e. residual heparin) Effect: Slow rate of thrombin generation leading to slow clot development Insufficient thrombin generation leading to insufficient clot development

Causes of enzymatic pathway abnormalities Coagulation factor deficiency Hemodilution Liver disease or liver congestion Trauma with significant blood loss and/or blood salvage Congenital – i.e. hemophilia Factor consumption > synthesis Cardiopulmonary bypass, ECMO Disseminated intravascular coagulation (DIC) Coagulation factor dysfunction Vitamin K deficiency Warfarin treatment Presence of anticoagulant Residual heparin

Enzymatic pathway abnormality: Coagulation factor deficiency Patient status: bleeding Patient condition: bleeding Probable cause: factor deficiency Probable cause: Factor deficiency

Enzymatic pathway abnormality: Coagulation factor deficiency Patient status: bleeding Probable cause(s): Factor deficiency Platelet deficiency/dysfunction

Enzymatic pathway abnormality: Coagulation factor deficiency Patient status: bleeding Probable cause(s)  Common treatment(s) Factor deficiency  FFP Platelet deficiency/dysfunction  platelets

Enzymatic pathway abnormality: Residual heparin Characterized by a bleeding patient and a TEG tracing with an abnormally long R value (non-heparinase sample) Probable causes: Residual heparin after protamine administration due to insufficient protamine dose. Heparin rebound – reappearance of heparin in circulation after initial reversal with protamine Release of endogenous sources of heparin (i.e. reperfusion of transplanted liver) Effect: inhibition of thrombin action resulting in reduced fibrin formation and clot development.

Enzymatic pathway abnormality: Residual heparin Post Protamine Patient status: Bleeding Probable cause(s): Residual heparin Factor deficiency First TEST for residual heparin

Testing for residual heparin with the TEG analyzer Run blood sample on two channels simultaneously K = kaolin activated (clear cup) KH = kaolin with heparinase (blue cup) Results: If R for K  KH, long R is not due to heparin If R for K is long and for KH is normal, heparin is present in blood sample

Testing for residual heparin with the TEG analyzer R for K > KH suggests presence of heparin

Fibrinogen deficiency Characterized by a bleeding patient and a TEG tracing with only an abnormally low angle (a). Probable cause: low fibrinogen levels Effect: slow rate of clot development Note: The angle parameter is influenced by the enzymatic and platelet pathways, thus correcting a deficiency or defect in these pathways will typically correct the angle.

Causes of fibrinogen deficiency Liver disease or congestion Disseminated intravascular coagulation (DIC) – hypocoagulable stage OB-GYN complications – placental abruption Hemodilution Excessive consumption

Fibrinogen deficiency Patient status: bleeding Probable cause: fibrinogen deficiency

Fibrinogen deficiency Patient status: Bleeding Probable cause: Fibrinogen deficiency Common treatment: Cryoprecipitate or FFP

Platelet abnormality Characterized by a bleeding patient and a TEG tracing with an abnormally low MA value A low MA value may also be associated with an elongated R and/or a low angle values Probable causes: Low platelet number Low platelet function Note: The TEG cannot distinguish between a low platelet count and low platelet function Effect: formation of a clot with low clot strength that is insufficient to stop vascular bleeding.

Platelet abnormality: A note on low platelet counts In certain disease states platelet counts may be reduced, but the remaining platelets may be hyperfunctional and hypersensitive, resulting in normal or high clot strength (normal to high MA). Example: cancer patients

Platelet abnormality Low platelet counts - causes Bone marrow disorders (i.e. leukemia) Chemotherapy Congenital disorder Lupus Trauma with significant blood loss and/or blood salvage Hemodilution Cardiac valve dysfunction – regurgitation Consumption and/or sequestration Platelet antibodies - HITT

Platelet abnormality Platelet dysfunction - Mechanisms Activation – inhibition or dysfunction of platelet receptors Adhesion – inhibition or dysfunction of GPIb receptor preventing adhesion of platelet to endothelium Aggregation – inhibition or dysfunction of GPIIb/IIIa receptors preventing the development of a platelet plug Secretion – inhibition or dysfunction of secretory pathways resulting in reduced platelet activation Procoagulant activity – reduction of thrombin generation on platelet surface

Platelet abnormality Low platelet function - causes Cardiopulmonary bypass Antiplatelet therapies Platelet antibodies Congenital disorders Liver disease Uremia Consumption

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s): Low platelet count +/or Low platelet function

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s)  Common treatments: Low platelet count  platelet transfusion Low platelet function  platelet transfusion

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s): Low platelet count +/or Low platelet function

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s)  Common treatment Low platelet count  platelet transfusion Low platelet function  platelet transfusion

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s): Factor deficiency +/or Low platelet count +/or Low platelet function

Patient status: bleeding Platelet abnormality Patient status: bleeding Probable cause(s)  Common treatment(s): Factor deficiency  FFP +/or Low platelet count  platelet transfusion Low platelet function  platelet transfusion

Platelet abnormalities Special considerations The inhibition of platelets by platelet inhibitors may not be revealed by the TEG using a kaolin activated sample. This is due to thrombin generation in the blood sample which results in maximum activation of platelets which overrides other activation pathways. An important factor to consider in induced platelet dysfunction (i.e., treatment with antiplatelet drugs) is the monitoring of platelet inhibition. PlateletMapping™ assays measure the degree of inhibition at the ADP receptor and arachadonic acid pathways as well as provide a reference point against which to interpret the inhibition (See Module 6)

Interpretation Exercises Hemorrhage

Exercise 1 Answer Next Black tracing: Kaolin Green tracing: Kaolin with heparinase Using the TEG Decision Tree, what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal Has heparin been reversed in this patient? Yes or No. Answer Next

Patient status: bleeding Exercise 2 Post-protamine Patient status: bleeding Using the TEG Decision Tree, what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal What treatment(s) would you consider for this patient? Answer Next

Patient status: Bleeding Exercise 3 Patient status: Bleeding Using the TEG Decision Tree and the available information from the TEG tracing: Is it likely the patient will require more protamine as a treatment for bleeding? Yes or No. Is it likely the patient will require FFP as a treatment for bleeding? Yes or No. Next Answer

Patient status: Bleeding Exercise 4 Patient status: Bleeding Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Surgical bleeding What treatment(s) would you consider for this patient? Answer Next

Exercise 5 Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal If this patient was bleeding, what treatment(s) would you consider? Answer Next

Patient status: bleeding Exercise 6 Post-protamine Patient status: bleeding Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Anticoagulant effect Platelet deficiency or dysfunction Low fibrinogen level Surgical bleeding What treatment(s) would you consider for this patient? Answer Next

Patient status: bleeding Exercise 7 Black tracing: Kaolin Green tracing: Kaolin with heparinase Patient status: bleeding Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Anticoagulant effect Platelet deficiency or dysfunction Low fibrinogen level Surgical bleeding How would you treat this patient? Answer Next

Exercise 8 Post-protamine - The above patient is bleeding after administration of protamine. What are the possible causes of bleeding (select all that apply)? - For each selection, identify one treatment consideration. Surgical bleeding Factor deficiency Residual platelet inhibitor effect Diminished platelet adhesion Anticoagulant effect Answer Next

Exercise 9 The above is the baseline TEG (post-induction) of a female patient (70 yr, 54kg) requiring CABG with CPB. The patient has not been taking aspirin for 7 days (81 mg/d). Based on this TEG and the patient history, is this patient at risk for bleeding post-CPB? Yes or No. If so, what will be the most likely cause(s) of bleeding? Surgical bleeding Factor deficiency Platelet deficiency/dysfunction Fibrinolysis Anticoagulant effect Answer Next

Exercise 10 Green: Post-protamine Black: ICU The above patient has started bleeding approximately 1 hr post-op. What is the most likely cause(s) of bleeding? Surgical bleeding Factor deficiency Platelet deficiency/dysfunction Fibrinolysis Anticoagulant effect How would you treat this patient? Answer END

Exercise 1 Back Black tracing: Kaolin Green tracing: Kaolin with heparinase Using the TEG Decision Tree what is your interpretation of this TEG tracing? Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal – all parameters are within normal range Has heparin been reversed in this patient? Yes or No. Since the R values for both the kaolin and kaolin with heparinase samples are the same suggests that the heparin has been reversed. Back

Patient status: bleeding Exercise 2 Post-protamine Patient status: bleeding Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal What treatment(s) would you consider for this patient? After completion of protamine administration, consider treating with platelets first. Repeat TEG. If R value is still elongated and the patient is bleeding, consider treating with FFP. Back

Patient status: Bleeding Exercise 3 Patient status: Bleeding Using the TEG Decision Tree and the available information from the TEG tracing: Is it likely the patient will require more protamine as a treatment for bleeding? Yes or No. This is a tracing from a kaolin activated sample. The presence of heparin in a kaolin sample would result in an elongated R value. An R within normal range suggests heparin is not present, thus additional protamine is not required. Is it likely the patient will require FFP as a treatment for bleeding? Yes or No. An R value within normal range suggests that factor deficiency is not the cause of bleeding in this patient. Back

Patient status: Bleeding Exercise 4 Patient status: Bleeding Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Surgical bleeding A slightly elongated R may suggest factor deficiency, however surgical bleeding cannot be ruled out. What treatment(s) would you consider for this patient? The R value is less than the trigger point for FFP transfusion. If patient is oozing, wait an hour and repeat the TEG. If R is still elongated and the patient is still oozy, consider treating with FFP. Back

Exercise 5 Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Platelet deficiency or dysfunction Low fibrinogen level Fibrinolysis Normal If this patient was bleeding, what treatment(s) would you consider? Cryoprecipitate or FFP Back

Patient status: bleeding Exercise 6 Post-protamine Patient status: bleeding Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency Anticoagulant effect Platelet deficiency or dysfunction Low fibrinogen level Surgical bleeding What treatment(s) would you consider for this patient? Platelet transfusion Back

Patient status: bleeding Exercise 7 Black tracing: Kaolin Green tracing: Kaolin with heparinase Patient status: bleeding Using the TEG Decision Tree what is your interpretation of this TEG tracing? [Select all that apply] Factor deficiency (cannot rule out) Anticoagulant effect (incomplete reversal of heparin) Platelet deficiency or dysfunction (cannot rule out) Low fibrinogen level Surgical bleeding How would you treat this patient? A common treatment protocol would likely include administration of additional protamine to reverse the heparin effect. If the patient continues to bleed, repeat the TEG to determine the probable cause. Most likely platelet deficiency/dysfunction. Back

Exercise 8 Post-protamine - The above patient is bleeding after administration of protamine. What are the possible causes of bleeding (select all that apply)? - For each selection, identify one treatment consideration. Surgical bleeding: check for bleeding site and repair Factor deficiency Residual platelet inhibitor effect: platelet transfusion Diminished platelet adhesion: DDAVP Anticoagulant effect: Since this is a KH sample, there is a possibility of residual heparin. Compare R values for the K and KH samples. If they are similar, the cause of bleeding is not residual heparin. Back

Exercise 9 The above is the baseline TEG (post-induction) of a female patient (70 yr, 54kg) requiring CABG with CPB. The patient has not been taking aspirin for 7 days (81 mg/d). Based on this TEG and the patient history, is this patient at risk for bleeding post-CPB? Yes or No. If so, what will be the most likely cause(s) of bleeding? Surgical bleeding Factor deficiency (cannot be ruled out) Platelet deficiency/dysfunction (Most likely cause of post-CPB bleeding since the patient is starting out with a low platelet count/function. Consider using aprotinin as antifibrinolytic agent. Rewarming TEG should demonstrate effect of CPB on platelets and factors). Fibrinolysis Anticoagulant effect Back

Exercise 10 Green: Post-protamine Black: ICU The above patient has started bleeding approximately 1 hr post-op. What is the most likely cause(s) of bleeding? Surgical bleeding Factor deficiency Platelet deficiency/dysfunction Fibrinolysis Anticoagulant effect (since kaolin sample, a heparin effect is not considered) How would you treat this patient? Return to OR for re-exploration. Back

End of Module 3