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Pharmacology Case Presentation
Margaret Baldwin, PharmD, BCPS
Pharmacist, Intermountain Medical Center, Intermountain Healthcare; Salt Lake City, Utah
Objectives: • Review new antithrombotics on the market • List new antithrombotics in the pipline • Discuss how these new medications will impact patient care
Clinical Application of Thromboelastography
Margaret Baldwin, PharmD, BCPSCritical Care Clinical PharmacistShock Trauma ICUIntermountain Medical Center
Objectives
Review how to interpret thromboelastography (TEG)
Discuss how anticoagulant and antiplateletmedications affect TEG results
Evaluate TEG and it’s implication to pharmacologic therapy
Clot Formation
http://www.thrombosisadviser.com/en/image.php?image=fibrinolysis-clot-formation&category=haemostasis .Accessed 3/13/14
Normal TEG Tracing
Adapted from Haemonetics Corporation educational material 8/5/2013 Dan Mason
Interpreting TEG
Value Definition Normal rangeSP Initial thrombin burstR End of thrombin burst 5-10 minutesDelta R-SP = thrombin burst 0.7-1.1K Fibrinogen function /crosslinking 1-3 minutesAngle Speed of clot strength 53-72 degreesMA Clot strength 50-70 mmG Mathematical conversion of MA 4.5-11 Kdynes/cm2
EPL Clot breakdown 0-15%LY30 Lysis 30 minutes after MA is reached 0-8%
SP = split point, time to first fibrin strands
R = reaction time to end of thrombin burst
R-SP = Delta = thrombin burst
K = fibrin cross-linkage, fibrinogen function
Angle = fibrinogen function
MA = platelet function in mm
G = MA converted to Kdynes/cm2
EPL = estimated percent lysis, clot breakdown
LY30 = lysis 30 minutes after MA reached
EPL, LY30
G = clot strength
= platelet function
R
K
Adapted from Haemonetics Corporation educational material 8/5/2013 Dan Mason
Platelet Mapping
Uses the patient’s baseline platelet activity as a reference
Effect of antiplatelet drug therapy Pathologic platelet dysfunction Help determine the cause of decreased MA
Platelet Mapping
Evaluate both platelet adhesion and aggregation Arachidonic acid (AA)
Evaluates adhesion Not applied to anything, just look at percent
Adenosine diphosphate (ADP) Evaluates aggregation Apply percent inhibition to the TEG G to calculate the
actual platelet function G integrity of the platelet
Reported in percent of platelet inhibition
Thrombelastograph ParametersMA Thrombin - Maximum clot strength induced by thrombin
MA Fibrin - Maximum contribution of fibrin only to MA
MA ADP or A.A - Measures ADP or arachidonic acid stimulated clot strength
0 MinutesAdapted from Haemonetics Corporation educational material 8/5/2013 Dan Mason
Applying TEG
Hyperfibrinolysis
Confidential Report for Improvement of Hospital, Facility and Patient Care--Not Part of Medical Record and Not to be Used in Litigation--Prepared Pursuant to Utah Code Ann. ? 26-25-1 et seq., or Idaho Code Ann. ? 39-1392 et seq.
28.2 79.1
Tranexamic Acid (TXA)
Inhibits lysine dependent plasminogen conversion to plasmin
Dosing 1000 mg IV over 10 minutes, then 1000 mg IV infusion over 8 hours
Lancet. 2011; 377:1096-1101J Trauma Acute Care Surg. 2013; 74(6): 1575-1586Arch Surg. 2012; 147: 113-119Drugs. 2012;72:585-617
CRASH-2 Trial Results
*
*
* P < 0.05
Effects of tranexamic acid on death, vascular occlusiveevents, and blood transfusion in trauma patients withsignificant haemorrhage (CRASH-2): a randomised,
placebo-controlled trial
Lancet. 2011; 377:1096-1101Arch Surg. 2012; 147: 113-119
NNT = 67
TXA reduced all-cause mortality and death due to bleeding with no risk of increased thromboembolic events
Hyperfibrinolysis
Confidential Report for Improvement of Hospital, Facility and Patient Care--Not Part of Medical Record and Not to be Used in Litigation--Prepared Pursuant to Utah Code Ann. ? 26-25-1 et seq., or Idaho Code Ann. ? 39-1392 et seq.
Hypercoagulable
Confidential Report for Improvement of Hospital, Facility and Patient Care--Not Part of Medical Record and Not to be Used in Litigation--Prepared Pursuant to Utah Code Ann. ? 26-25-1 et seq., or Idaho Code Ann. ? 39-1392 et seq.
Platelet Mapping
Confidential Report for Improvement of Hospital, Facility and Patient Care--Not Part of Medical Record and Not to be Used in Litigation--Prepared Pursuant to Utah Code Ann. ? 26-25-1 et seq., or Idaho Code Ann. ? 39-1392 et seq.
Desmopressin (DDAVP)
Synthetic vasopressin analog Used in patients with hemophilia A and von
Willebrand disease Prevents surgical bleeding in uremic patients Improves adhesion and enzymatic function
by increasing vWF and factor VIII Dosing
0.3 mcg/kg IV over 30 minutes Max 20 mcg
Platelet Mapping after DDAVP
Confidential Report for Improvement of Hospital, Facility and Patient Care--Not Part of Medical Record and Not to be Used in Litigation--Prepared Pursuant to Utah Code Ann. ? 26-25-1 et seq., or Idaho Code Ann. ? 39-1392 et seq.
Pattern Recognition
http://www.st-marys-anaesthesia.co.uk/Guidelines/Basic_Guide_to_TEG_Interpretation.pdf
What Blood Product To Give
EPL, LY30
= platelet function
R
K
Cryoprecipitate Platelets+/- DDAVP
FFP AntifibrinolyticsTranexamic Acid
Thrombin
Clot Initiation
Clot Strength
Clot Stability
Fibrinogen
Adapted from Haemonetics Corporation educational material 8/5/2013 Dan Mason
Patient Case
Trauma 1 Activation on 12/17
MM is a 21 year old female who rear-ended a UTA bus at full speed. She was unrestrained and required prolonged extrication from under the dashboard of her vehicle.
PMH was not significant NKDA MM drinks alcohol regularly, smokes 1 pack
of cigarettes per day and admits to occasional marijuana use
Hemodynamically stable Multiple abrasions and lacerations Severe distress secondary to pain and
difficulty breathing Quite anxious
Physical Findings
Radiologic Findings
CT chest shows non-displaced bilateral 4th rib fractures
CT abdomen and pelvis shows a large grade V liver laceration with associated intraperitoneal bleeding, but no evidence of active extravasation
X-rays of knees show bilateral patellar fractures, right open and left closed
Laboratory Data
CMP Na 142, K 2.6, Cl 114, CO2 15, Gluc 132, BUN 5,
SCr 1.19, ALT 593, and AST 586
BAL 76, lactate 6.1, INR 1.3, amylase 60, and lipase 96
Urine drug screen is positive for cannabinoids TEG
Platelet mapping
R SP K Angle MA G LY302.7 2.4 1.3 72.2 61.8 8.1 1.0
ADP inhibition AA inhibition66.4% 12%
MM’s Course
12/17 OR for washout and ORIF of patella, returns to the ICU
12/18-12/21 in ICU with minimal improvement
12/22 OR for evacuation of hemoperitoneumwith placement of 2 peri-hepatic drains TEG
Platelet mapping
Enoxaparin 60 mg SubQ BID (0.75 mg/kg)
R SP K Angle MA G LY304.8 3.8 1.1 72.1 80.2 20.2 0
ADP inhibition AA inhibition100% 69.9%
MM’s Course 12/23
TEG
Enoxaparin 80 mg SubQ BID (1 mg/kg) Started clopidogrel 75 mg PO daily
12/24 TEG
No changes made
R SP K Angle MA G LY303.9 3.8 0.9 78.3 77.1 16.8 0.1
R SP K Angle MA G LY304.6 4.2 1.1 75.8 77.9 17.6 1.3
MM’s Course
12/25 TEG
Platelet mapping
Enoxaparin 120 mg SubQ BID (1.5 mg/kg)
R SP K Angle MA G LY303.9 3.9 0.8 76.3 77.3 17 0.5
ADP inhibition AA inhibition100% 47%
MM’s Course
12/26 TEG
Discharged home Enoxaparin 150 mg SubQ BID (~2 mg/kg) Clopidogrel 75 mg PO daily
R SP K Angle MA G LY303.9 3.7 0.8 78.3 78.1 17.8 0.2
12/27 MM Returns Comes to the ED because she is bleeding
from peri-hepatic drain, in severe distress, and hypotensive
CT abdomen shows a grade V liver laceration with active extravasation to the upper abdomen with expanded intraperitoneal hemorrhage
CT chest shows a large right pneumothorax TEG
INR 1.2 HCT 21.9
R SP K Angle MA G LY303.8 3.7 0.8 81.7 84 26.2 0
MM’s Second Course
Meds Given Protamine 100 mg IV x1 DDAVP 25 mcg IV x1
Blood 5 units pRBCs with good hemodynamic response Progressed MTP activation
Angio Emergent embolization of liver Chest tube placement
MM’s Second Course 12/29
TEG
12/30 TEG
DDAVP 25 mcg/kg IV once Back to OR for evacuation of hemoperitoneum
12/31-1/4 Started on heparin 5000 units SubQ TID
R SP K Angle MA G LY303.3 3.0 1.1 74.5 74.2 14.4 0.7
R SP K Angle MA G LY303.6 3.2 1.0 75.7 75.4 15.3 1.1
TEG
May provide rapid and more complete diagnostic information
Similar cost to the standard laboratory tests Clinical management of severe bleeding with
TEG may reduce transfusion-related risks May optimize the use of healthcare resources Does not replace standard of care monitoring
for anticoagulants
Cochrane Database Syst Rev. 2011;3
Questions
Clinical Application of Thromboelastography
Margaret Baldwin, PharmD, BCPSCritical Care Clinical PharmacistShock Trauma ICUIntermountain Medical Center