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