Heparin-Instigated Thrombocytopenia.

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DVT in a Breast Cancer Patient. 69-year-old lady, first Dx Breast Ca in 2002, on and off chemotherapy most recent 2 years for intermittent pleural metastases First left leg DVT in March
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Heparin-Induced Thrombocytopenia Lawrence Rice, MD Chief, Division of Hematology Clinical Chief, Hem/Onc Service The Methodist Hospital Weill Cornell Medical College Houston, Texas

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DVT in a Breast Cancer Patient 69-year-old lady, first Dx Breast Ca in 2002, on and off chemotherapy most recent 2 years for recurrent pleural metastases First left leg DVT in March \'06 July \'06 Admitted for dynamic leg agony and swelling, more terrible DVT, in spite of outpatient warfarin Rx IV heparin, IVC channel (platelets 350K) Two weeks later: Discharged on warfarin (platelets 81K; had been ~80K most recent a few days)

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HIT With Cancer

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Some Lessons from this Case HIT is a typical issue HIT incites a great danger for genuine thrombotic intricacies Unopposed warfarin builds this danger IVC channels ought to be maintained a strategic distance from Alternative anticoagulants ought to be begun speedily Therefore, clinicians must be very educated and stay cautious for HIT

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There are more than 100 HIT stories in the Medical Center each year…

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Frequency of HIT Perspectives More than 1 trillion units heparin utilized yearly as a part of US; 1/3 of hospitalized uncovered (12 million) Unfractionated heparin – 3 - 5% incidence; Heart surgery 2.5% rate LMWHeparin, Catheter-flushes - ~0.5% Warkentin, NEJM \'95, 11/332 SQ heparin v. 0/333 LMWH created HIT Laster, 1988, 10/2,000 (0.5%) HIT presented just to covered vascular catheter Frequency of thromboemboli – 30-75%

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Some Paradoxes of HIT Heparin, the most capable anticoagulant of the twentieth Century, sparing uncountable lives and appendages, likewise delivers the most great hypercoagulable issue, costing thousands yearly their lives and appendages. HIT, a resistant response to an anticoagulant that brings down platelet tally, once in a while causes dying, it causes thromboses,(and platelet transfusions are contraindicated). Wellbeing experts ought to be proficient around a response that is regular, frequently disastrous, preventable, treatable, iatrogenic, and a noteworthy wellspring of case, yet course books and medicinal curriculae give careful consideration, and winning absence of mindfulness is stunning.

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IgG counter acting agent PF4 Heparin Formation of safe edifices (PF4-heparin-IgG) Formation of PF4-heparin buildings Microparticle discharge EC harm Platelet PF4 discharge Platelet activation* Heparin-like particles Fc receptor Blood vessel Heparin-Induced Thrombocytopenia (HIT): Pathophysiology 1 *Places quiet at more serious danger from essential thrombotic issue. 1. Adjusted from Aster RH. N Engl J Med . 1995;332(20):1374-1376.

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Sequelae Incidence New thromboses ~50% (arterial or venous) Amputation ~21% Death ~30% Heparin-Induced Thrombocytopenia (HIT): Clinical Consequences if Untreated 1. Warkentin TE, Kelton JG. Am J Med. 2. Ruler DJ, Kelton JG. Ann Intern Med.

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Risk of Thrombosis with HIT After Heparin is Stopped (if a compelling option is not started) 100 90 80 70 60 50 40 30 20 10 0 52.8% Cumulative recurrence of thrombosis (%) 10 12 14 16 18 20 22 24 26 28 30 0 2 4 6 8 Days after separated HIT perceived Warkentin and Kelton. Am J Med 1996;101.

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HIT is a Clinico-Pathologic Syndrome Fall in platelet numbers (for the most part >50%) Appropriate time after heparin start (5-12 days) Extreme danger for venous or blood vessel thromboembolic entanglements Eventually: Serologic affirmation of platelet-actuating heparin-PF4 antibodies

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Clinical Suspicion for HIT The 4 T\'s (Warkentin, 2003) Thrombocytopenia Timing Thrombosis oTher reasons for low platelets grant 0–2 focuses for how common for HIT high prob 6–8 pts; intermed 4-5; low 0-3 The 5 th T: The Test

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Heparin (re) Exposure Typical HIT Mean Day 9 (4 – 14 days) Rapid-onset HIT (hours – days) Delayed-onset HIT (9 – 40 days) Day 1 Day 4 Day 14 Day 30 THROMBOCYTOPENIA (± THROMBOSIS) HIT Temporal Variants Courtesy of Dr Ahjad AlMahameed Cleveland Clinic, OH.

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Distribution of Platelet Count Warkentin. Semin Hematol 1998;35(4):9-16.

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Laboratory Tests for Heparin-PF4 Antibodies Commercially accessible ELISAs Highly delicate (95-99%); High "false positive" rates; titer vital Serotonin-discharge assays Technically requesting; variety lab- to-lab; restricted accessibility Platelet conglomeration assays Poor reproducibility Multiple others Flow cytometry or fluorescence-based Rapid bedside immunoassays Newer tests being developed

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ACCP Antithrombotic Guidelines Chest supplement, Sept. 2004, Chapter on HIT: Monitoring, Dx and Rx Examples of Evidence-Based Recommendations: "postoperative prophylaxis with UFheparin (HIT hazard > 1%), no less than each other day platelet tally checking between post-operation days 4-14 or until UFH is halted (2C)" "postoperative prophylaxis with LMWheparin (HIT hazard 0.1-1%), platelet tally observing each 2 to 3 days between days 4-14 (2C)"

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Treatment of Other Drug-Induced Thrombocytopenias Stop the medication Consider platelet transfusions Consider different measures to decrease draining danger Once platelets rise, the response is over Stop all heparin exposures Initiate an option anticoagulant on suspicion Do NOT transfuse platelets; start warfarin early Risk of thrombosis develops weeks after platelet recuperation Treatment of Heparin-Induced Thrombocytopenia Rice L. Curve Intern Med. 2004;164:1961-1964.

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Alternative Anticoagulants

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The Key to Avoiding Catastrophes from HIT is Awareness, Vigilance, High Degree of Suspicion Consider HIT amid/not long after heparin exposure* When a patient... encounters a drop in platelet checks creates thrombosis * Heparin presentation might be through for all intents and purposes any arrangement (counting LMWH), any measurement, or any course of heparin (counting flushes and covered lines)

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HIT Summary A particular clinico-pathologic disorder Common—among most regular causes of thrombocytopenia in doctor\'s facility Serious, dependably conceivably calamitous Unique pathophysiology and testing Unique entanglement profile: Thromboemboli Unique administration: alternative anticoagulants

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Proposed ICD-9 CM New Code 289.84 Heparin-initiated thrombocytopenia (HIT) another 5 digit subclassification code as takes after: 287 Purpura and other hemorrhagic conditions 287.4 Secondary thrombocytopenia Post-transfusion purpura Thrombocytopenia (because of): Dilutional Drugs Extracorporeal flow of blood Platelet alloimmunization Use expansion E code to distinguish cause Add Excludes: Heparin-actuated thrombocytopenia (289.84)

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Proposed ICD-9 CM another 5 digit subclassification code as takes after: 289 Other infections of blood and blood-framing organs 289.8 other indicated maladies of blood and blood-shaping organs 289.81 Primary hypercoagulable state 289.82 Secondary hypercoagulable state Add Excludes: Heparin-instigated thrombocytopenia (289.84) 289.83 Myleofibrosis New Code 289.84 Heparin-incited thrombocytopenia (HIT)

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