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

Back

Next

Post-protamine,Cup temperature: 37.1°C

End of module 4