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Slide 2 Anthony Worsham, MD Friday, June 18, 2010 Hospital Medicine Best Practices Meeting University of New Mexico Slide 3 Case vignette Background Pathophysiology Guidelines Action recommendations Discussion with Dr. Garcia Slide 4 44-year-old man HPI: ESRD secondary to DMII, CAD CC: sepsis/osteomyelitis Hospital course: osteomyelitis treated with piperacillin/tazobactam right subclavian catheter-associated DVT treated with heparin drip Orthopedics consulted; BKA scheduled was switched to argatroban due to platelet drop morning prior to surgery, patient went into PEA arrest and ACLS protocol initiated, but patient died. Slide 5 Slide 6 73-year-old female transferred for workup of a possible left adnexal mass multiple abdominal surgeries at St. Vincent's secondary to necrotizing fasciitis as well as multiple abdominal abscesses several decubitus ulcers with wound VAC pulmonary embolism at outside hospital on a heparin drip MDR UTI with Klebsiella, Pseudomonas, Candida and VRE malnutrition Slide 7 Slide 8 Slide 9 formerly known as HIT Type II thrombocytopenia absolute: 1 wk v LMWH>fondaparinux) (OR~10-15), type of patient (surgery>medical>pregnancy) OR ~3-4, higher risk in women (odds ratio, 1.5 2.0) Timing: 5-10 days post heparin exposure Mechanism Platelet activation by binding of heparin-dependent IgG to platelet FcIIa receptors Slide 10 Slide 11 Slide 12 Slide 13 Venous thromboembolism DVT (50%) and pulmonary embolism (25%) Arterial thrombosis Limb artery thrombosis (10%15), thrombotic stroke (5%10%), myocardial infarction (3%5%), other (eg, mesenteric artery thrombosis, spinal artery thrombosis) Thrombotic stroke Coumarin necrosis Adrenal hemorrhage Necrotizing skin lesions at heparin injection sites Anaphylactoid reaction DIC 10%20% of patients who have HIT have overt (decompensated) DIC (eg, hypofibrinogenemia, increased INR, positive protamine sulfate paracoagulation Warkentin TE, Heparin-induced thrombocytopenia, Hematol Oncol Clin N Am 21 (2007) 589607 Slide 14 Differential diagnosis Sepsis DIC TTP/HUS Drug-induced Antibiotics Heparin (see OSU website) ITP Slide 15 2 points1 point0 points Thrombocytopenia>50% fall or nadir 20-100 x 10 9 /L 30-50% fall or nadir 10-19 x 10 9 /L functional assay: serotonin release assay (SRA) gold standard technically demanding, requires radiation Send out lab sensitive and specific (>95%) antigen immunoassays enzyme-linked immunosorbent assay [ELISA] high sensitivity, low specificity PIFA (Particle ImmunoFiltration Assay) Platelet aggregation assay HIPA (heparin-induced platelet aggregation) Results not immediately available for any test Slide 18 Warkentin TE, et al. Am J Med. 1996;101:502-507. Slide 19 Initial treatment decisions made on clinical grounds Confirm thrombocytopenia (repeat CBC) Test for DIC Test for HIT antibodies Assess for thromboses (eg, ultrasound for lower-limb DVT) Stop all heparin (including heparin flushes and, possibly, use of heparin-coated intravascular catheters [catheters in situ for several days may not have significant residual heparin) Initiate alternative anticoagulation (options: argatroban, lepirudin, bivalirudin, fondaparinux [?]) if HIT is strongly suspected Slide 20 Di Nisio M, et al. Direct thrombin inhibitors. NEJM 2005;353:1028-40. Slide 21 Exosite 1 = dock for substrates such as fibrin Exosite 2 = heparin binding domain Slide 22 argatroban hepatically cleared lepirudin renally cleared ?higher risk of bleeds bivalirudin Mostly used during cardiac surgery Di Nisio M, et al. Direct thrombin inhibitors. NEJM 2005;353:1028-40. argatroban: thrombosis decreased to 13-19% vs 35% historical controls; bleeding rate 6-11% lepirudin: thrombosis decreased to 4% vs 15% historical controls; bleeding rate 14% bivalirudin: mostly used during PCI or cardiothoracic surgery Slide 23 postpone warfarin until platelet count > 150 10 9 /L warfarin and DTI should overlap 4-5-days target INR for concomitant warfarin/argatroban 4.0 Warkentin T et al,Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest June 2008 133:340S-380S Slide 24 Slide 25 Slide 26 Slide 27 Slide 28 Slide 29 Slide 30 When should hematology consult be obtained? Would placing a HIT protocol in CPOE be helpful?