Basic Clinician TrainingModule 4
Special circumstances:
Distinguishing between different causes of bleeding
Bleeding: special circumstances• Hemodilution vs. Hypothermia
• von Willebrand factor deficiency vs. Surgical bleeding
• Protamine overdose
Hemodilution vs. Hypothermia
Hemodilution vs. Hypothermia
Hemodilution• Implementation
Hematocrit < 25%• Circumstances:
• of blood conservation techniques Blood volume expansion Cardiopulmonary bypass
• Likely to affect factors and platelets the same.
Hypothermia• Core temperature <34°C• Circumstances:
Exposure to the cold Induced for clinical purposes Administration of large volume of fluids that are cold or at room temperature
• May not demonstrate same effect on factors and platelets, depends on temperature.
Hemodilution• Reduction in the
concentration of hemostatic factors and cellular hemostatic components.
Hypothermia• At 33°C the likely cause of
bleeding is a reduction in platelet aggregation and adhesion.
• At < 33°C the likely cause of bleeding also includes reduced enzymatic function and platelet activation
Hemodilution vs. HypothermiaMechanisms of Coagulapathy
[Wolberg AS, et. al. J Trauma. 2004;56:1221.]
Hemodilution vs. HypothermiaDifferentiation and Treatments
Hemodilution• Identification: low HCT,
normal temperature• Common treatment:
Hemoconcentration, if possible FFP for factor deficiency Platelet transfusion for platelet deficiency
Hypothermia• Identification: Core
temperature < 34°C, normal or low HCT.
• Common treatment: Warm patient to > 36°C Treat factor deficiency or platelet dysfunction if required (i.e. abnormal TEG tracing at normal temperature setting (37°C)).
• Run blood sample on two channels simultaneously Channel 1: cup temperature set at 37°C Channel 2: adjust cup temperature to patient
core temperature• Results:
If Channel 1 (37°C) sample is normal and Channel 2 abnormal, bleeding is due to hypothermia and should subside with rewarming.
If both Channel 1 (37°C) and Channel 2 samples demonstrate a coagulapathy, treat with appropriate blood products or hemostatic agents until the 37°C sample is normalized.
Hypothermia:Determining impact on coagulation
Hypothermia:Determining impact on coagulation
Black: cup temperature 37°CGreen: cup temperature set at patienttemperature (33°C)
Patient bleeding likely due to hypothermia
Hemodilution vs. HypothermiaTEG analysis
Patient status: bleeding
Hemodilution vs. Hypothermia? A single TEG tracing cannot distinguish.•If patient temperature is > 35°C and HCT < 25%, bleeding is likely due to hemo-dilution. Treat accordingly.•If patient temperature is < 34°C, bleeding is likely due to hypothermia. Compare TEGsrun at patient temperature and at 37°C. Treat accordingly.
Hemodilution vs. Hypothermia?TEG analysis
Cup temperature: 37°C
Patient status: bleeding
Probable cause(s):• Hemodilution +/or• Factor deficiency +/or• Platelet deficiency/dysfunction
Hemodilution vs. Hypothermia?TEG analysis
Cup temperature: 33.4°C
Patient status: bleeding
Probable cause(s):• Hypothermia +/or • Factor deficiency +/or• Platelet deficiency/dysfunction
vWF deficiency vs. Surgical bleeding
von Willebrand factor (vWF) deficiency• vWF
Deficiency is associated with a FVIIIc deficiency Required for platelet adhesion to vessel wall via
the GP1b receptor.• Circumstances:
Congential Acquired
• Cardiopulmonary bypass• Chronic aortic stenosis• Malignancy
• Coagulapathy is due to reduced platelet adhesion to vessel wall, manifested as microvascular bleeding.
vWF deficiency:TEG analysis
Patient status: bleeding
Since vWF deficiency results in a plateletadhesion defect, the TEG tracing will be normal.
Other possible causes of bleeding: • Presence of platelet inhibitor• Vessel injury
vWF deficiency:TEG analysis
Patient status: bleeding
Probable causes Common treatments• vWF deficiency DDAVP• Presence of platelet inhibitor Platelet transfusion• Vessel injury Suture
vWF deficiency vs. Surgical bleeding?
• Both cases: TEG tracing is normal but patient is bleeding
• Distinguishing vWF deficiency from surgical bleeding: vWF deficiency: appears microvascular in nature Surgical bleeding: generally more profuse and localized
• Common treatments vWF deficiency
• Consider treatment with DDAVP– Diminished bleeding post treatment suggestive of vWF deficiency
• Consider cryoprecipitate Surgical bleeding: bleeding from small surgical sites
• May diminish with time• May respond to continuous product transfusion
Protamine overdose
Protamine
• Neutralizes heparin via an ionic interaction 1 mg protamine neutralizes 1 mg heparin
• Protamine administration protocols vary. Typical range: 1.0 – 1.3 mg/ 100 units heparin 0.5 – 1.0 mg/kg body wt
• Protamine alone, or not bound to heparin, has a mild anticoagulant effect
Possible mechanisms of protamine anticoagulant effect.
• Inhibits the proteolytic activity of thrombin in a dose-dependent and reversible manner
• Decreases platelet count• Impairs in vitro response to ADP,
epinephrine, and thrombin• Also releases tPA from endothelial cells
Speiss, BD et al. Perioperative Transfusion Medicine. 1998.
Protamine anticoagulation effect
• Protamine doses > 2.0 mg/100 units heparin could cause bleeding Clinical significance of protamine anticoagulation
effect is debatable• Protamine doses between 1.3 – 1.5 mg/100 units
heparin may result in an in vitro, but not an in vivo anticoagulant effect. If the patient is bleeding, this in vitro effect could
mask the true cause of bleeding as indicated by TEG analysis.
• Prudent to avoid administration of protamine doses beyond the amount required neutralize heparin. TEG analysis can demonstrate heparin reversal by
protamine
In vitro protamine effectTEG analysis
Post protamine
Patient status: not bleeding
• Protamine dose > 1.3 mg/100 units heparin • In vitro effect demonstrated in both Kaolin and Kaolin with heparinase samples
In vitro protamine effectTEG analysis
Black: 1 hr post-opGreen: post-protamine
• A TEG was repeated 1 hr post-op in the ICU. The in vitro protamine effectwas no demonstrated.
Interpretation Exercises
Hemorrhage – Special Cases
Exercise 1: Trauma patient in ER
Black: cup temperature @ 37.1°CGreen: cup temperature @ patient temperature (32.9°C)
Using the TEG Decision Tree, what is (are) the possible cause(s) of bleeding in this patient?
[Select all that apply]a. Factor deficiencyb. Platelet deficiency or dysfunctionc. Hypothermia d. Hemodilutione. Anticoagulant effect
Answer
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Exercise 2: Trauma patient in the ER
The above patient came into the ER with a core temperature of 35.8°C. The patient has received 2.5 L of crystalloid volume. The patient is now hemodynamically stable, but his core temperature is 34.3°C and he has started to bleed. What would be the best treatment option for this patient at this time to stop the bleeding?
a. Lasix b. FFPc. Plateletsd. Warm patient to > 35.5°C e. DDAVP
What additional information would help you with your decision?
Answer
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Exercise 3
Post-protamine
The above 47 yr patient (male, aortic valve replacement) is bleeding after administration of protamine. All suture sites appear to be intact. What is (are) the most likely cause(s) of bleedingin this patient? (select all that apply)
a. Surgical bleedingb. Factor deficiencyc. Residual platelet inhibitor effectd. Anticoagulant effecte. Diminished platelet adhesion
What additional information would help with your decision?
Answer
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Exercise 4
Select all the possible causes of bleeding that could be indicated by the above TEG tracing and indicate an how you could differentiate between the different causes.
a. Surgical bleedingb. Factor deficiencyc. Platelet dysfunctiond. Anticoagulant effecte. Hypothermina
cup temperature @ 37.1°C
Answer
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Exercise 5Post-protamine,Cup temperature: 37.1°C
The above TEG was performed post-protamine. The patient is dry and the surgeon is ready toclose the patient. The surgeon has asked for the results of the TEG. How would you explainthe above tracing?
a. Poor sampling technique or preparationb. Hemodilution c. Hypothermina effectd. Residual heparine. In vitro protamine effect
Answer
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Exercise 1: Trauma patient in ER
Black: cup temperature @ 37.1°CGreen: cup temperature @ patient temperature (34.6°C)
Using the TEG Decision Tree, what is (are) the possible cause(s) of bleeding in this patient? [Select all that apply]
a. Factor deficiency – could be result of bleeding plus crystalloid or colloid volume replacement.
b. Platelet deficiency or dysfunction – could be result of bleeding plus crystalloid or colloid volume replacement.
c. Hypothermia – not a primary cause of bleeding since both cups demonstrate similar coagulapathy. Transfusion of warmed fluids is recommended to diminish further drop in core temperature
d. Hemodilution – result of bleeding plus crystalloid or colloid volume replacement leading to factor and platelet deficiency.
e. Anticoagulant effect
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Exercise 2: Trauma patient in the ER
The above patient came into the ER with a core temperature of 35.8°C. The patient has received 2.5 L of crystalloid volume. The patient is now hemodynamically stable, but his core temperature is 34.3°C and he has started to bleed. What would be the best treatment option for this patient at this time to stop the bleeding?
a. Lasix – although the patient may be hemodiluted, it is not the main cause of bleeding.
b. Cryoprecipitatec. Plateletsd. Warm patient to > 35.5°C – best and least costly treatment option at this time. e. DDAVP – there could be a possible platelet adhesion defect in this patient What additional information would help you with your decision? Run a TEG at34.3°C to determine if coagulapathy is temperature-related.
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Exercise 3
Post-protamine
The above 47 yr patient (male, aortic valve replacement) is bleeding after administration of protamine. All suture sites appear to be intact. What is (are) the most likely cause(s) of bleedingin this patient? (select all that apply) a. Surgical bleedingb. Factor deficiencyc. Residual platelet inhibitor effectd. Anticoagulant effecte. Diminished platelet adhesion – this is the most likely cause of bleeding, unless the patient was taking platelet inhibitors for vascular disease. Considertreatment with DDAVP.What additional information would help with your decision? Current medicationssuch as platelet inhibitors, or a family history of vWD.
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Exercise 4
Select all the possible causes of bleeding that could be indicated by the above TEG tracing and indicate a common treatment for each cause.• Surgical bleeding• Factor deficiency – elongated R suggests factor deficiency. A likely cause is hemodilution.Common treatment: FFP• Platelet dysfunction – low MA suggests platelet dysfunction. This couldbe due to a variety of factors, including hemodilution or a decrease in platelet number due to sequestration or loss of platelets. Commontreatment: platelet transfusion• Anticoagulant effect – the elongated R also suggests residual heparin, especially since it is a KH sample. Common treatment: protamine• Hypothermina – cannot be completely ruled out, but not likely.
cup temperature @ 37.1°C
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Exercise 5
The above TEG was performed post-protamine. The patient is dry and the surgeon is ready toclose the patient. The surgeon has asked for the results of the TEG. How would you explainthe above tracing?
a. Poor sampling technique or preparation – possible, but uncommon cause.b. Hemodilutionc. Hypothermina effectd. Residual heparine. In vitro protamine effect – check with anesthesia for protamine ratio usedto reverse the heparin
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Post-protamine,Cup temperature: 37.1°C
End of module 4