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    Heparin Induced Thrombocytopenia 2009

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    pannumd
    This document provides information on heparin induced thrombocytopenia (HIT). It begins with an overview of the pathophysiology of HIT, noting that it is an immune-mediated reaction where heparin complexes with platelet factor 4, generating antibodies that activate platelets and endothelial cells, resulting in thrombosis. It then discusses three clinical cases presenting with thrombocytopenia after heparin exposure. The document emphasizes the importance of promptly diagnosing and treating HIT to prevent thrombotic complications. It reviews treatment options and considerations for patients with HIT requiring cardiac or vascular surgery.

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    Heparin Induced Thrombocytopenia 2009

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    pannumd
    39 views49 pages
    This document provides information on heparin induced thrombocytopenia (HIT). It begins with an overview of the pathophysiology of HIT, noting that it is an immune-mediated reaction where heparin complexes with platelet factor 4, generating antibodies that activate platelets and endothelial cells, resulting in thrombosis. It then discusses three clinical cases presenting with thrombocytopenia after heparin exposure. The document emphasizes the importance of promptly diagnosing and treating HIT to prevent thrombotic complications. It reviews treatment options and considerations for patients with HIT requiring cardiac or vascular surgery.

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    heparin induced throbocytopenia

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    HIT 2009 Final

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    This document provides information on heparin induced thrombocytopenia (HIT). It begins with an overview of the pathophysiology of HIT, noting that it is an immune-mediated reaction where heparin complexes with platelet factor 4, generating antibodies that activate platelets and endothelial cells, resulting in thrombosis. It then discusses three clinical cases presenting with thrombocytopenia after heparin exposure. The document emphasizes the importance of promptly diagnosing and treating HIT to prevent thrombotic complications. It reviews treatment options and considerations for patients with HIT requiring cardiac or vascular surgery.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    39 views49 pages

    Heparin Induced Thrombocytopenia 2009

    Uploaded by

    pannumd
    This document provides information on heparin induced thrombocytopenia (HIT). It begins with an overview of the pathophysiology of HIT, noting that it is an immune-mediated reaction where heparin complexes with platelet factor 4, generating antibodies that activate platelets and endothelial cells, resulting in thrombosis. It then discusses three clinical cases presenting with thrombocytopenia after heparin exposure. The document emphasizes the importance of promptly diagnosing and treating HIT to prevent thrombotic complications. It reviews treatment options and considerations for patients with HIT requiring cardiac or vascular surgery.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 49

    Heparin Induced Thrombocytopenia 2009

    Robert D. McBane II Division of Cardiology Gonda Vascular Center Mayo Clinic Rochester

    Disclosure Information

    Heparin Induced Thrombocytopenia


    Robert McBane, MD

    None

    Resources
    Treatment and Prevention of Heparin-Induced Thrombocytopenia: Evidence-Based Clinical Practice Guidelines American College of Chest Physicians

    http://www.chestjournal.org/cgi/reprint/133/6_suppl/340S

    Objectives
    Background Recognition Diagnosis Management

    Prothrombotic nature of HIT: Comparison with other thrombophilia


    Thrombophilia HIT
    Factor V Leiden Protein C deficiency Protein S deficiency AT deficiency Dysfibrinogenemia Lupus anticoagulant

    Odds ratio for thrombosis


    36.9 6.6 14.4 10.9 24.1 11.3 5.4

    Warkentin:1995,2003

    Pathophysiology of H.I.T.

    PF4

    GAG Endothelium

    Pathophysiology of H.I.T.
    Heparin PF4:Heparin Complexes

    PF4

    GAG Endothelium

    Pathophysiology of H.I.T.
    HIT antibodies

    Pathophysiology of H.I.T.
    Platelet
    FC Receptor

    a granule

    Pathophysiology of H.I.T.
    HIT Antibodies

    Endothelial Injury
    GAG Endothelium

    Case 1
    76 year old male 3 month history of progressive chest pain 3 day history of angina at rest Admitted to Cardiology service No prior medical assessment

    Case 1
    Platelet Count (x109/L) 300 250 200 150 100 50 0

    Heparin

    5
    Days

    10

    11

    Case 1
    The next most appropriate step in this patients management would be: 1. Stop all heparin products 2. Obtain Heparin-platelet factor 4 ELISA 3. Begin direct thrombin inhibitor 4. No change in anticoagulants is necessary

    Case 1
    The next most appropriate step in this patients management would be: 1. Stop all heparin products 2. Obtain Heparin-platelet factor 4 ELISA 3. Begin direct thrombin inhibitor 4. No change in anticoagulants is necessary

    Heparin-Induced Thrombocytopenia Type I: Non-immune

    t ~1-4 days Platelets 100-150,000 Recovery despite heparin

    Not symptomatic
    Platelet agglutination

    HIT Terminology
    Isolated HIT: Type II, Immune thrombocytopenia

    Asymptomatic Onset ~ 5 14 days Thrombocytopenia persists until heparin stopped


    HITT: HIT thrombosis Arterial or venous thromboembolism new / progressive

    H.I.T.: Clinical Spectrum


    Venous Thrombosis DVT PE Phlegmasia Dolens Cerebral Sinus Thrombosis Arterial Thrombosis Acute Limb Ischemia Stroke MI Mesenteric Ischemia Miscellaneous Adrenal Hemorrhage Heparin Skin Necrosis 50% 25% 5% Rare 10% 5% 5% Rare Rare Rare

    Case 2
    62 y/o woman
    Right ovarian mass Preoperative workup: Severe mitral valve stenosis MVR: metallic prosthesis Chronic warfarin One month later admitted for TAH-BSO

    Case 2
    Admitted to Gynecology service for transitioning warfarin to UFH

    Case 3
    Platelet Count (x109/L) 300 250 200 150 100 50 0

    Heparin
    Thrombotic Stroke

    Lepirudin > warfarin

    5
    Days

    10

    11

    HIT Terminology
    Rapid Onset HIT (25 30%)

    Occurs < 24 hours after exposure History of prior heparin exposure within past 100 days Results from circulating HIT antibodies Not amnestic response Check baseline CBC and repeat within 24 hours if prior
    heparin exposure (within 100 days)

    Case 3
    74 yr Male
    3/21 Right Total Knee Arthroplasty
    (DVT prophylaxis: Unfractionate Heparin, SCDs, Teds)

    3/23

    Physical therapy initiated

    3/28

    Uneventful hospital discharge

    Case 3
    4/3 Develops cough and slight dyspnea

    4/4

    Notes right leg swelling


    US CTA Extensive DVT Multiple PE

    Case 3
    Management options in the ED include:
    1. 2. 3. 4. 5. Initiate outpatient LMW-heparin Admit for inpatient Unfractionated heparin Admit for argatroban therapy Obtain Heparin PF 4 antibodies Need more clinical information

    Case 3
    Management options in the ED include:
    1. 2. 3. 4. 5. Initiate outpatient LMW-heparin Admit for inpatient Unfractionated heparin Admit for argatroban therapy Obtain Heparin PF 4 antibodies Need more clinical information

    Case 3
    Laboratory Assessment: CBC: Hgb 11.0 WBC 8.1 Platelet 132

    Creatinine: 1.2

    Case 3
    Platelet Count (x109/L) 425 375 300 225 150 75 0

    5
    Days

    10

    11

    HIT Terminology
    Delayed Onset HIT (3-5%)

    Occurs several days after heparin discontinued Always obtain platelet count prior to starting heparin Review history for heparin exposure (past 100 days)
    and recent platelet data

    Objectives
    Background Recognition Diagnosis Management

    Immune H.I.T. Type II


    Look for
    Thrombocytopenia

    Is there
    > 50% fall Nadir 20-100

    Timing

    5-10 days < 1day (prior heparin)


    New event Skin necrosis None

    Thrombosis Other causes

    Heparin PF4 ELISA


    Relatively easily performed Sensitivity > 90% Specificity ~ 50% False negative: heparin therapy

    Objectives
    Background Recognition Diagnosis Management

    Case 5
    75 year old woman Admitted with community acquired pneumonia Received subcutaneous UFH prophylaxis

    Case 5
    Platelet Count (x109/L) 300 250 200 150 100 50 0

    Heparin

    5
    Days

    10

    11

    Case 5
    The heparin PF-4 ELISA was strongly positive, consistent with the diagnosis of isolated HIT. After stopping all heparin, which of the following is the most acceptable next step?
    1. Start enoxaparin now 2. Start argatroban now 3. Start argatroban and warfarin now 4. Search for thrombosis and if present start lepirudin

    Case 5
    The heparin PF-4 ELISA was strongly positive, consistent with the diagnosis of isolated HIT. After stopping all heparin, which of the following is the most acceptable next step?
    1. Start enoxaparin now 2. Start argatroban now 3. Start argatroban and warfarin now 4. Search for thrombosis and if present start lepirudin

    Natural History of H.I.T.


    100 Cumulative Thrombotic Event Rate 80 60 40 20 0 2 6 10 14 18 22 26 Days after Diagnosis of H.I.T. 30
    Am J Med 96;101:502

    52.8%

    HIT Treatment
    Argatroban
    Hepatic excretion

    Lepirudin
    Renal excretion

    Warfarin
    Do not start until platelet count >100 Do not load (max dose 5 mg) Overlap with DTI for 5 days

    Case 6
    74 year old male with recent outside diagnosis of HIT. He is transferred to your cardiovascular service with progressive angina. Coronary angiography discloses severe three vessel disease with EF 35%. Which of the following is the most acceptable next step?

    1. Proceed with CABG now using argatroban 2. Proceed with CABG now using bivalirudin 3. Proceed with CABG now using lepirudin 4. Postpone for 3 months and repeat ELISA 5. Repeat ELISA now

    Case 6
    74 year old male with recent outside diagnosis of HIT. He is transferred to your cardiovascular service with progressive angina. Coronary angiography discloses severe three vessel disease with EF 35%. Which of the following is the most acceptable next step?

    1. Proceed with CABG now using argatroban 2. Proceed with CABG now using bivalirudin 3. Proceed with CABG now using lepirudin 4. Postpone for 3 months and repeat ELISA 5. Repeat ELISA now

    HIT and Cardiopulmonary Bypass


    HIT antibodies
    Weak or undetected by 100 days Not regenerated with brief re-exposure Restrict heparin to CPB use only safe*

    *Nuttall et al. Anesth Analg. 2003 Feb;96(2):344-50

    Patients With Prior HIT Undergoing Cardiac or Vascular Surgery


    HIT ELISA antibody negative UFH is preferred over a non-heparin anticoagulant (Grade 1B).

    CHEST 2008; 133:340S380S

    Patients With Prior HIT Undergoing Cardiac or Vascular Surgery


    ELISA positive but platelet activation assay negative: UFH is preferred over a non-heparin anticoagulant (Grade 2C). Preoperative and postoperative anticoagulation, if indicated, should be given with a non-heparin anticoagulant.

    CHEST 2008; 133:340S380S

    Patients With Acute HIT Undergoing Cardiac or Vascular Surgery


    ELISA positive : Delay surgery (if possible) until HIT has resolved and antibodies are negative [Grade 1B] Bivalirudin [Grade 1B] Lepirudin [Grade 2C]

    CHEST 2008; 133:340S380S

    Bivalirudin (Angiomax)
    Direct thrombin inhibitor Short T: 25 min Proteolytic inactivation
    minor renal excretion (20%)

    ACT monitored Several Studies


    EVOLUTION-OFF EVOLUTION-ON
    J Thorac Cardiovasc Surg 2006; 131:686692

    J Thorac Cardiovasc Surg 2006; 131:533539

    Bivalirudin during cardiopulmonary bypass in patients with HIT: CHOOSE-ON trial


    Open-label, multicenter 49 patients On pump
    Primary endpoints (day 7/discharge) Death 1 (2.0%) Q-wave MI 0 (0.0%) Revascularization 1 (2.0%) Stroke 1 (2.0%)
    Intra op blood loss 24 hr blood loss Transfusion RBC Plts FFP 575524 ml 998595 ml 4.75.3 U 6.58.8 U 5.85.5 U

    Ann Thorac Surg 2007; 83:572577

    Off-Pump Coronary Artery Bypass With Bivalirudin for patients with HIT: CHOOSE-OFF trial Open-label, multicenter 51 patients Off pump
    Primary endpoints (day 7/discharge) Death 0 Q-wave MI 3 (6%) Revascularization 0 Stroke 1 (2.0%)
    Intra op blood loss 24 hr blood loss Transfusion RBC Plts FFP 404420 ml 936525 ml 5.63.8 U 8.67.2 U 6.04.7 U

    Ann Thorac Surg. 2007;84:836-9

    Heparin Induced Thrombocytopenia After Cardiac Surgery


    When to think of HIT post CPB:
    Platelet count falls by >50% New thrombotic event Especially between days 5 and 14 Perform pre-test probability assessment [Grade 1C]
    CHEST 2008; 133:340S380S

    Conclusion
    Immune mediated Common

    Clinically important thrombosis risk


    Awareness monitor platelet count

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