Heparin Pathologies

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Heparin Pathologies
Presented by Maggie Savelberg, Group
Members Desiree Bonadonna and Britt
McIlwain University of Nebraska Medical
Center Omaha, Nebraska
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Overview
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Introduction
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Coagulation Anticoagulation
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Heparin
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Resistance Rebound
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Allergic Rxns HIT
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SOP
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World Knowledge
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Introduction

• Cardiac surgery requiring cardiopulmonary bypass
  (CPB) places a large burden of activation of the
  hemostatic coagulation system

Caused by..
Re-infusion of pericardial blood exposed to
thrombogenic surfaces
Blood foreign circuitry interface Blood-air
interface
Effects of microemboli on endothelial cells
Decrease in circulating protein buffers
(Speiss et al., 2008)
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Introduction
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Introduction
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Anticoagulation
Elevated hemostatic activity without
anticoagulation is associated with CPB may induce
a systemic inflammatory reaction and lead to
Therefore, adequate anticoagulation is a critical
component of successful management of hemostatic
and inflammatory responses associated with CPB.
(Parekh, 2008)
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Coagulation
Understanding current concepts of coagulation is
important in determining the preoperative
bleeding risk of patients and in managing
hemostatic therapy perioperatively. (Tanaka
KA., 2009)
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Coagulation
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Anticoagulation
Although the immature systems of neonates needs
further study, according to Gruenwald et al.,
2010 (Sick Kids Hospital Toronto) She can
conclude definitively that individualized heparin
and protamine management in pediatrics has been
shown to reduce platelet activation and
coagulopathies.
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So how should anticoagulation during CPB be
managed and what other pathologies associated
with heparinization for anticoagulation, be
understood and accounted for?
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Anticoagulation
1.
2.
3.
(Hirsh, 2001)
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Heparin
(Hirsh, 2001)
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Heparin
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Heparin
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Heparin
(Hirsh, 2001)
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Heparin
(Hirsh, 2001)
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Heparin
Venous thromboembolism Prophylaxis of DVT and
PE Treatment of DVT Coronary heart disease UA
and Acute MI
(Hirsh, 2001)
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Heparin Dosing
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Anticoagulation Management
(Lobato, 2010)
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Anticoagulation Monitoring
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Anticoagulation Monitoring
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Anticoagulation Monitoring
(Dunning, 2008)
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Anticoagulation Monitoring
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Anticoagulation Monitoring
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Anticoagulation Management
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Anticoagulation Management
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Heparin Resistance
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Heparin Resistance
Heparin Resistance
(Speiss et al., 2008)
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Heparin Resistance
Heparin Resistance
(Leong, et al. 1998)
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Heparin Resistance
Heparin Resistance
(Leong, et al. 1998)
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Heparin Resistance
Heparin Resistance
(Leong, et al. 1998)
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Heparin Resistance
Heparin Resistance
SOP Recommendations for AT III dosing are 100
x (weight in kgs) to increase AT III levels from
0 to 100. (Gravlee, 1993)
(Speiss et al., 2008)
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Heparin Rebound
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Heparin Rebound
43 of CPB Patients
(Teoh, 2004) (Subramaniam, 2008)
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Heparin Rebound
Heparin Rebound Effect
(Teoh, 2004)
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Heparin Rebound
Heparin Rebound
1.
(Teoh , 2004)
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Heparin Rebound
(Ferraris , 2007)
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Heparin Allergy
Heparin Rebound
(Subramaniam, 2008)
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Heparin Rebound
(Subramaniam, 2008)
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Heparin Allergy
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Heparin Allergy
Type III Reactions
(Jappe, 2008)
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Heparin Allergy
(Jappe, 2008)
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Heparin Allergy
Type I Reactions
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Heparin Allergy HIT
HIT 1
HIT 2
(1) Cheng, D.., (2006) Perioperative Care in
Cardiac Anesthesia and Surgery. Chp 19 HIT and
Alternatives to Heparin Table taken from pg.174,
(2) (Gurbuz, A.T., et al., 2005) European
Journal of Cardio-thoracic Surgery 27138-149
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Heparin Allergy HIT 2
Caused by heparin-dependent immunoglobin G (IgG)
antibodies (HIT-IgG) binding to a
conformationally modified epitope on platelet
factor 4 (PF4) antibodies present in 18 of
patients exposed to UFH (Gurbuz, 2004) The
binding of heparin and other glycosaminoglycans
to PF4 heparin-PF4 complex, alters its shape
rendering it immunogenic. Against which IgG
antibodies are formed. (Antigenicity of the
heparin-PF4 complex depends on the molecular
weight and degree of sulfation of the heparin
molecule.)
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Heparin/PF4 Complex
PF4 Complex
IgG antibody
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HIT The big picture
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HIT Diagnosis

• 1. Thrombocytopenia during heparin therapy.
• Note Thrombocytopenia during first 4
  post-operative days of cardiac surgery due to
  hemodilution and platelet consumption is rarely
  HIT related.
• 2. Exclusion of other causes of thrombocytopenia
  i.e. septicemia, MOF (multi-organ
  failure),post-transfusion purpura.
• 3. Diagnosis confirmed by
• a) Detection of HIT-IgG antibodies by ELISA, for
  heparin-PF4 complexes using goat anti-human
  antibody (antigen assay)
• b) Or by a heparin-induced platelet aggregation
  study (HIPAA)
• 4. Resolution of thrombocytopenia after cessation
  of heparin.

ELISA Plate
Gurbuz, et al. (2005) Heparin Induced
Thrombocytopenia in the Cardiovascular Patient
Diagnostic and Treatment Guidelines, Eur. J of
Card-Thor Surg. 27138
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Heparin Allergy
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World Knowledge
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World Knowledge

• R.Britt McILwain BS RRT CCP UAB Medical Center
  Birmingham, Alabama
• Dosing
• Patients lt18 y of age 400 units/kg
• Adults 300 units/kg
• Target ACT Adults (480 s)
• POC testing iStat
• Mgt
• Anesthesia and Perfusion communicate.
• Adults ACTs
• Pediatrics Hepcon (helps account for dilutional
  effect with low BSAs)
• Brand APP Pharmaceuticals
• Coating Yes, but no change to target ACTs.
• Hemoconcentrate many patients may pull off too
  much heparin decreased hep conc.

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World Knowledge

• Desiree Bonadonna CCP, LP, BSE
• Duke University Hospital
• Durham, NC
• Dosing
• Patients (Avg wt) 30,000 IU
• Smaller and larger 300 IU/kg calculated
• Target ACT Adults (400 s) due to Actalyke
  reporting lower but more accurate values
  (Welsby, 2002)
• POC testing Actalyke ACT analyzer Model A2P by
  Helena Laboratories with the MaxACT tube .
• Mgt
• Perfusion and anesthesia Re-dose at 20 of
  loading dose when ACT low.
• Coating Not heparin coated.

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World Knowledge
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World Knowledge
Target ACT for CPB Initiation ?
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World Knowledge
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World Knowledge
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World Knowledge
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Thank you!