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Heparin Induced Thrombocytopenia Handout

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Heparin Induced Thrombocytopenia Handout

  1. 1. Heparin-Induced Thrombocytopenia: A Case Presentation Darcie Gampetro Pharm.D Candidate 2011 September 2010
  2. 2. Patient JB <ul><li>Pt is a 45 y.o. female who presents with acute respiratory failure. </li></ul><ul><li>Pt was recently hospitalized for possible BOOP and concomitant pseudomonas infection (9/5-9/10) </li></ul><ul><ul><li>Medications upon discharge: </li></ul></ul><ul><ul><ul><li>TMP/SMX </li></ul></ul></ul><ul><ul><ul><li>Ciprofloxacin </li></ul></ul></ul><ul><ul><ul><li>Voriconazole </li></ul></ul></ul><ul><ul><ul><li>*On 9/11 platelet count was 220,000 </li></ul></ul></ul><ul><li>Social History: </li></ul><ul><ul><li>Lives with husband and 15 year old son </li></ul></ul><ul><ul><li>Has 27 year old daughter </li></ul></ul><ul><ul><li>30-pack-year smoking history </li></ul></ul><ul><ul><li>History of alcoholism-currently sober for 2 months </li></ul></ul><ul><li>Allergies </li></ul><ul><ul><li>Doxycycline </li></ul></ul><ul><ul><li>Fentanyl </li></ul></ul><ul><ul><li>Hydoxyzine </li></ul></ul><ul><ul><li>Ketorolac </li></ul></ul><ul><ul><li>Nalbuphine </li></ul></ul><ul><ul><li>NSAIDs </li></ul></ul>
  3. 3. Patient JB <ul><li>Chest x-ray showed worsening of bilateral diffuse interstitial infiltrates </li></ul><ul><li>Significant lab values: </li></ul><ul><ul><li>BP=168/124 </li></ul></ul><ul><ul><li>Pulse=127 </li></ul></ul><ul><ul><li>Respiratory rate=44 </li></ul></ul><ul><ul><li>O2 saturation=49% </li></ul></ul><ul><ul><li>WBC=20.1 </li></ul></ul><ul><ul><li>Hgb=9.6 </li></ul></ul><ul><ul><li>Hct=28.2 </li></ul></ul><ul><ul><li>plt:=138,000 platelets/ μ L </li></ul></ul><ul><ul><li>Scr=1.7 </li></ul></ul><ul><ul><li>BUN=35 </li></ul></ul><ul><ul><li>Glucose=256 </li></ul></ul><ul><ul><li>BNP=361 </li></ul></ul><ul><li>Review of Systems: </li></ul><ul><ul><li>Mostly unobtainable as pt was placed on Bipap </li></ul></ul><ul><li>Height: 66 in </li></ul><ul><li>Weight: 72.9 kg </li></ul><ul><li>pH 7.23, pCO2 57, pO2 67, bicarb 24 </li></ul>
  4. 4. JB Past Medical History <ul><li>Type I Diabetes Mellitus </li></ul><ul><li>Bronchiolitis Obliterans Organizing Pneumonia (BOOP) </li></ul><ul><li>Cirrhosis with liver decompensation and renal insufficiency related to alcoholism—complicated by steatohepatitis, fribrosis and coagulopathy </li></ul><ul><li>Depression with anxiety-previous suicide attempt with drug overdose </li></ul><ul><li>Anorexia </li></ul><ul><li>Chronic abdominal pain </li></ul><ul><li>Pancreatitis in 2007 </li></ul><ul><li>Carpal tunnel surgery </li></ul><ul><li>C-section two times </li></ul><ul><li>Cholescystectomy in 2007 </li></ul><ul><li>Tubal ligation </li></ul><ul><li>Adenoidectomy in 2006 </li></ul><ul><li>Colonoscopy in 2008 </li></ul>
  5. 5. Home Medications <ul><li>Guaifenesin 600mg po daily </li></ul><ul><li>Trimethoprim sulfamethoxazole 1 DS tab daily </li></ul><ul><li>Prednisone 30 mg po daily </li></ul><ul><li>Mylanta 30 mL po prn </li></ul><ul><li>Magic mouthwash 30 mL po prn </li></ul><ul><li>Voriconazole 200 mg po q12h </li></ul><ul><li>Nicoderm 7 mg patch daily </li></ul><ul><li>Methadone 60 mg po tid with meals </li></ul><ul><li>Ciprofloxacin 500 mg po bid </li></ul><ul><li>Ursodiol 300 mg po tid </li></ul><ul><li>Oxycodone 5 mg 2-3 tablets po tid prn </li></ul><ul><li>Omeprazole 40 mg po daily </li></ul><ul><li>Vitamin E 1000 units po daily </li></ul><ul><li>Glucagon 1 mg subcutaneously one time as needed </li></ul><ul><li>Vitamin D 50,000 unitis po q 7 days </li></ul><ul><li>Lantus 32 units subcutaneously daily qam </li></ul><ul><li>Promethazine 25 mg tid prn </li></ul><ul><li>Lorazepam 0.5 mg po bid prn </li></ul><ul><li>Polyethylene glycol one 17 gm packet po daily prn </li></ul><ul><li>Metoclopramide 10 mg po qid prn </li></ul><ul><li>Multivitamin one tablet po daily </li></ul><ul><li>Novolog correction scale </li></ul>
  6. 6. Inpatient Medications Day 1 <ul><li>Furosemide </li></ul><ul><li>Methadone </li></ul><ul><li>Lansoprazole </li></ul><ul><li>Phyontadione </li></ul><ul><li>Albuterol </li></ul><ul><li>Guaifenesin </li></ul><ul><li>Propofol </li></ul><ul><li>Hydromorphone </li></ul><ul><li>Methylprednisolone </li></ul><ul><li>Insulin </li></ul><ul><li>Enoxaparin </li></ul>
  7. 7. Day 2 Medication Changes <ul><li>Enoxaparin changed to heparin due to hepatic decompensation and renal insufficiency </li></ul><ul><li>Pipercillin/Tazobactam added </li></ul><ul><li>Esomeprazole added </li></ul><ul><li>Metoclopramide added </li></ul>
  8. 8. Day 4 <ul><li>4 doses of heparin given from 9/14-9/15 </li></ul><ul><li>Platelets: </li></ul><ul><ul><li>9/14: 104,000 platelets/ μ L </li></ul></ul><ul><ul><li>9/15: 94,000 platelets/ μ L </li></ul></ul><ul><ul><li>9/16:78,000 platelets/ μ L </li></ul></ul>
  9. 9. Heparin-Induced Thrombocytopenia Topic Discussion
  10. 10. Heparin-Induced Thrombocytopenia (HIT) <ul><li>Decreased platelet count during or following heparin therapy </li></ul><ul><ul><li><150,000 platelets/ μ L </li></ul></ul><ul><ul><li>50% decrease from baseline </li></ul></ul><ul><li>Onset may be rapid or delayed </li></ul><ul><li>Mechanism of immune response </li></ul><ul><ul><li>Heparin binds to platelet factor 4 (PF4) </li></ul></ul><ul><ul><li>IgG, IgM, and IgA antibodies generated </li></ul></ul><ul><ul><li>Complexes aggregate and are prematurely removed from circulation  thrombocytopenia </li></ul></ul><ul><ul><li>Platelet activation leads to prothrombotic platelet microparticles  promotes coagulation </li></ul></ul><ul><li>Two types of HIT </li></ul><ul><ul><li>Type 1 </li></ul></ul><ul><ul><ul><li>Benign form </li></ul></ul></ul><ul><ul><ul><li>Small decrease in platelet count occurring two days after initiation of heparin (platelet count usually >100,000 platelets/ μ L) </li></ul></ul></ul><ul><ul><ul><li>Platelet counts return to normal with continued heparin therapy </li></ul></ul></ul><ul><ul><li>Type 2 </li></ul></ul><ul><ul><ul><li>More serious form of HIT </li></ul></ul></ul><ul><ul><ul><li>Immune-mediated disorder with formation of antibodies against heparin-PF4 complex </li></ul></ul></ul><ul><ul><ul><li>Risk of thrombosis </li></ul></ul></ul>
  11. 11. Figure taken from Uptodate (see references
  12. 12. Type 2 HIT <ul><li>Factors strongly associated with development of HIT </li></ul><ul><ul><li>Long duration of therapy ( >4 days) </li></ul></ul><ul><ul><li>Use of UFH </li></ul></ul><ul><ul><li>Surgery patients </li></ul></ul><ul><ul><li>Female rather than male pts </li></ul></ul><ul><li>Thrombotic risk from HIT is more than 30x that of control population </li></ul><ul><li>Risk of thrombus remains high for days to weeks </li></ul>
  13. 13. Diagnosis of HIT <ul><li>Rule out other causes of thrombocytopenia </li></ul><ul><ul><li>Bacterial infection </li></ul></ul><ul><ul><li>Medications </li></ul></ul><ul><ul><li>Bone marrow disease </li></ul></ul><ul><li>Laboratory Diagnosis </li></ul><ul><ul><li>What abnormal values would we expect? </li></ul></ul>
  14. 14. Pretest Probability of HIT The 4 T’s <ul><li>Thrombocytopenia </li></ul><ul><li>Timing of platelet count fall </li></ul><ul><li>Thrombosis </li></ul><ul><li>Other causes for thrombocytopenia present? </li></ul>
  15. 15. The 4 T’s  Thrombocytopenia <ul><li>Platelet count fall > 50% and nadir >20,000: 2 points </li></ul><ul><li>Platelet count fall 30-50% or nadir 10-19,000: 1 point </li></ul><ul><li>Platelet count fall <30% or nadir <10,000: 0 points </li></ul>
  16. 16. The 4 T’s  Timing of platelet count fall <ul><li>Clear onset on days 5-10 or platelet count fall ≤1 day if previous heparin exposure within last 30 days: </li></ul><ul><li>2 points </li></ul><ul><li>Not clear fall on days 5-10 (missing platelet counts) or onset after day 10 or fall ≤1 day with previous heparin exposure within last 30-100 days: </li></ul><ul><li>1 point </li></ul><ul><li>Platelet count fall at <4 days without recent exposure: </li></ul><ul><li>0 points </li></ul>
  17. 17. The 4 T’s Thrombosis or other sequelae <ul><li>Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV UFH bolus: </li></ul><ul><li>2 points </li></ul><ul><li>Progressive or recurrent thrombosis, non-necrotizing skin lesions, or suspected thrombosis which has not been proven: </li></ul><ul><li>1 point </li></ul><ul><li>None: </li></ul><ul><li>0 points </li></ul>
  18. 18. The 4 T’s Other causes for thrombocytopenia present <ul><li>None apparent: 2 points </li></ul><ul><li>Possible: 1 point </li></ul><ul><li>Definite: 0 points </li></ul>
  19. 19. The 4 T’s Score <ul><li>Zero to 3: Low probability </li></ul><ul><li>4 to 5: Intermediate probability </li></ul><ul><li>6 to 8: High probability </li></ul>
  20. 20. Clinical Presentation <ul><li>What are the clinical manifestations of HIT? </li></ul><ul><li>Implications </li></ul><ul><ul><li>Mortality in 20-30% of patients with thrombosis </li></ul></ul><ul><ul><li>20-30% of patients will become permanently disabled </li></ul></ul>
  21. 21. Treatment <ul><li>Cessation of all formulations of heparin </li></ul><ul><li>Alternative anticoagulation </li></ul><ul><ul><li>Lepirudin (Refludan ®) </li></ul></ul><ul><ul><li>Bivalirudin (Angiomax ®) </li></ul></ul><ul><ul><li>Argatroban </li></ul></ul><ul><ul><li>Fondiparinux </li></ul></ul><ul><ul><li>Warfarin-once anticoagulated with other agent and platelets >150,000/ μ L </li></ul></ul><ul><li>Duration of anticoagulation </li></ul><ul><ul><li>Two to three months if no thrombotic event occurred </li></ul></ul><ul><ul><li>Six months if thrombotic event occurred </li></ul></ul>
  22. 22. Lepirudin (Refludan®) <ul><li>Recombinant Hirudin </li></ul><ul><li>Direct thrombin inhibitor </li></ul><ul><li>FDA labeled indication: anticoagulation in patients with HIT and associated thromboembolic disease in order to prevent further thromboembolic complications </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>Bolus: 0.4 mg/kg IVP over 15-20 seconds (max=44 mg) </li></ul></ul><ul><ul><li>Maintenance: 0.15 mg/kg/hr (16.5 mg/hr) </li></ul></ul><ul><ul><li>Reduce dose in renal impairment </li></ul></ul><ul><ul><li>Goal aPTT= 1.5-2.5 above baseline </li></ul></ul><ul><li>For conversion to oral anticoagulant, must be above 1.5x aPTT and overlap therapies 4 to 5 days </li></ul>
  23. 23. Bivalirudin (Angiomax®) <ul><li>Thrombin inhibitor </li></ul><ul><li>FDA labeled indications: anticoagulant used in conjunction with aspirin for patients with unstable angina undergoing percutaneous transluminal coronary angioplasty with provisional glycoprotein IIb/IIIa inhibitor; anticoagulant used in PCI or in patients at risk for HIT </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>Bolus: 0.75 mg/kg </li></ul></ul><ul><ul><li>Maintenance: 1.75 mg/kg/hr continuous infusion for up to 4 hours </li></ul></ul><ul><ul><li>If need further therapy, give 0.2 mg/kg/hr for up to 20 hours </li></ul></ul><ul><ul><li>Reduce dose in renal impairment </li></ul></ul>
  24. 24. Argatroban <ul><li>Direct thrombin inhibitor </li></ul><ul><li>FDA labeled indications: prophylaxis or treatment of thrombosis in patients with HIT; adjunct to percutaneous coronary intervention in patients who have or are at risk of thrombosis associated with HIT </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>2mcg/kg/min IV </li></ul></ul><ul><ul><li>Goal aPTT at steady state is 1.5-3 times the initial baseline value </li></ul></ul><ul><li>Can be used in patients with ESRD </li></ul>
  25. 25. Fondaparinux (Arixtra®) <ul><li>Factor Xa inhibitor </li></ul><ul><li>Not approved for use in HIT </li></ul><ul><li>Dosing: </li></ul><ul><ul><li>2.5 mg once daily </li></ul></ul><ul><li>Long half life </li></ul><ul><li>Renaly eliminated </li></ul>
  26. 26. Back to the case… <ul><li>What tests should be done in this patient? </li></ul><ul><li>What is our patients 4 T’s Score? </li></ul><ul><li>Is it likely to be HIT? If so, what type? </li></ul><ul><li>What are the options for anticoagulation in this patient? </li></ul>
  27. 27. Back to the case… <ul><li>Lab test ordered on 9/15 to determine presence of antibodies to heparinoid and PF4 complexes </li></ul><ul><li>On 9/16: </li></ul><ul><ul><li>heparin was discontinued </li></ul></ul><ul><ul><li>Pt received blood transfusion (2 units) </li></ul></ul><ul><li>On 9/17: </li></ul><ul><ul><li>platelet count decreased to 65,000 platelets/ μ L. </li></ul></ul><ul><li>On 9/18: </li></ul><ul><ul><li>Serology testing revealed 48% heparin dependent platelet antibiody reactivity </li></ul></ul><ul><ul><li>agatroban therapy was initiated. </li></ul></ul><ul><ul><li>platelet count rose to 80,000 platelets/ μ L </li></ul></ul><ul><li>Patient’s platelet count continues to rise 122,000 platelets/ μ L </li></ul>
  28. 28. Back to the case… <ul><li>What tests should be done in this patient? </li></ul><ul><ul><li>Platelets </li></ul></ul><ul><ul><li>Serum reactivity </li></ul></ul><ul><li>What is our patients 4 T’s Score? </li></ul><ul><ul><li>Thrombocytopenia (1 point)+ Timing (0 points) + thrombosis or other sequelae (0 points) + Other causes (1 point)= 2 points </li></ul></ul><ul><li>Is it likely to be HIT? If so, what type? </li></ul><ul><ul><ul><li>4 T’s score <3 </li></ul></ul></ul><ul><ul><ul><li>Occurred within 2 days </li></ul></ul></ul><ul><ul><ul><li>Platelet count was trending down previously </li></ul></ul></ul><ul><ul><ul><li>Pt has hepatic insufficiency and coagulopathy issues </li></ul></ul></ul><ul><li>What other options for anticoagulation in this patient could be considered? </li></ul>
  29. 29. St. Luke’s Policy
  30. 31. References <ul><li>Diaz, Josephina, et al. &quot;Profiling of heparin-induced thrombocytopenia antibody levels in patients with and without diabetes.&quot; Clinical and applied thrombosis/hemostasis 16.2 (2010):121-5. </li></ul><ul><li>Franchini, Massimo. &quot;Heparin-induced Thrombocytopenia: an Update.&quot; Thrombosis Journal . 04 Oct. 2005. Web. 20 Sept. 2010. <http://www.thrombosisjournal.com/content/3/1/14>. </li></ul><ul><li>Arepally, Gowthami M., and Thomas L. Ortel. &quot;Heparin-Induced Thrombocytopenia.&quot; New England Journal of Medicine 355.8 (2006): 809-17. 24 Aug. 2006. Web. 20 Sept. 2010 </li></ul><ul><li>Coutre, Steven. &quot;Heparin-Induced Thrombocytopenia.&quot; UpToDate Inc. 28 Jan. 2008. Web. 23 Sept. 2010. <http://www.uptodate.com/online/content/topic.do?topicKey=coagulat/8950&selectedTitle=1~150&source=search_result>. </li></ul><ul><li>  DiPiro, Joseph T. &quot;Hematologic Disorders.&quot; Pharmacotherapy: a Pathophysiologic Approach . New York: McGraw-Hill Medical, 2008. 1875-889. Print. </li></ul><ul><li>Micromedex DrugDex Index Search Term: Lepirudin </li></ul><ul><li>Micromedex DrugDex Index Search Term: Bivalirudin </li></ul><ul><li>Micromedex DrugDex Index Search Term: Argatroban </li></ul><ul><li>Micromedex DrugDex Index Search Term: Fondaparinux </li></ul><ul><li>Lexi-Drugs Search Term: Lepirudin </li></ul><ul><li>Lexi-Drugs Search Term: Bivalirudin </li></ul><ul><li>Lexi-Drugs Search Term: Argatroban </li></ul><ul><li>Lexi-Drugs Search Term: Fondaparinux </li></ul>

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