Endovascular Procedures in Cancer Patients with Chronic Thrombocytopenia Cezar Iliescu MD, FACC, FSCAI Director of the cardiac catheterization laboratory MDACC
No disclosures 2
Introduction Cancer and coronary artery disease CAD and chronic thrombocytopenia 3
Cancer incidence Cancer Facts & Figures 2010 4
Cancer Survival The percent of cancer survivors is increasing by: Early detection Better cancer treatment Improving Cardiovascular survival Cancer Facts & Figures 2010 5
Cancer and CAD Today, most cancers are linked to a few controllable factors: tobacco use poor diet lack of exercise infectious diseases Double Jeopardy 6
Cancer and thrombocytopenia ~140,000 patients Most of them will become thrombocytopenic during the treatment 7
CAD and thrombocytopenia Global Registry of Acute Coronary Events 1. incidence of thrombocytopenia after hospital admission 2. patient and treatment characteristics 3. outcomes in patients enrolled The American Journal of Cardiology January 2009 8
CAD and thrombocytopenia ACS patients were stratified into 4 groups: heparin-induced thrombocytopenia (HIT) 152 (0.3%), glycoprotein IIb/IIIa-associated thrombocytopenia (GAT) 324 (0.6%), other thrombocytopenia 368 (0.7%) no thrombocytopenia. The American Journal of Cardiology January 2009 9
CAD and thrombocytopenia Patients with HIT (OR 1.94, CI 1.07 to 3.53), GAT (OR 3.45, 95% CI 2.35 to 5.05), or other thrombocytopenia (OR 2.83, 95% CI 1.97 to 4.06) were significantly more likely to die in the hospital vs. those without these diseases They were also more likely to experience: major bleeding (re) infarction stroke The American Journal of Cardiology January 2009 10
Thrombocytopenia Marker of severity of disease: Sepsis, acute bleeding, HIT, GPIIbIIIa induced Chronic thrombocytopenia: s/p BMT MDS Chemo associated 21.9% - patients treated with taxane-based regimens 64.2% - patients treated with gemcitabine-based regimens. Other (chronic hepatitis) Wu Y, Clinical Therapeutics 2009 11
Thrombopoietin did not improve platelet counts in patients undergoing stem cell transplantation or acute leukemia induction Kuter DJ. Clinical Lymphoma & Myeloma 2009 12
Platelet transfusion ASCO guidelines <10,000/µL in adults receiving therapy for acute leukemia MDACC transplant patient <15,000/µL nonfebrile, nonbleeding thrombocytopenic transplant patient Entrenched practice prior to invasive procedures transfuse patients with platelets <50,000/µL Platelet count of 40,000-50,000/µL are sufficient for the safe performance of major invasive procedures A Alousi Transfusion support- Blood and Marrow Transplantation 2007 13
Do we need platelet transfusion? stored platelet products in the blood bank partial activation up-regulation of inflammatory mediators cellular morphology changes loss of cell membrane lipids and micro-particle formation apoptosis side effects: fever alloimmunisation sepsis thrombosis transfusion-related acute lung injury 14
Platelet transfusion Random donor platelets (RDP) (centrifugation) Single donor platelets (SDP) (apheresis) Leukoreduction? WBC: Neutrophil count Monocyte count JC Kaski Atherosclerosis June 2010 15
Platelet Function? Measure Platelet number Platelet size Platelet structure Platelet function Test Automated counter Automated counter Light and electron microscope Aggregation (LTA, WBA, VerifyNow Platelet-fibrin clot (TEG) Shear dependent plug (PFA-100) Activation-dependent signaling (VASP) Activation-dependent expression (Flow) Activation-dependent release (TX, PM, CCD40L) J. Eikelboom ESC 2009 16
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Platelet function Limitations: Test of in-vitro function Non-physiological stimulus and environment Measure an isolated aspect of platelet function Do not reflect the complicated nature of platelet physiology J. Eikelboom ESC 2009 18
Thrombocytopenia and thrombosis 19
Procedural and Intermediate Term Outcomes after Endovascular Procedures in Cancer Patients with Chronic Thrombocytopenia: First Case Series Cezar Iliescu MD Siddharth Mukerji MD Gloria Iliescu MD Guillherme Oliveira MD Wamique Yusuf MD Jean Bernard Durand MD 20
Demographics Total number of procedures 32 Total number of patients 31 Age 24-77 Mean 58.1 Gender W 12 M 19 21
Risk factors CAD/CV risk factors N 31 % Coronary artery disease 10 32 Hypertension 23 74 Dyslipidemia 22 71 Diabetes Mellitus 4 13 Heart Failure 10 32 Current/former smoker 6/11 19/36 22
Cancer diagnosis Leukemia 9 Lymphoma/MM 8 SCT 6 H&N 2 GI 2 Lung CA 2 Breast Ca 1 Sarcoma 1 74% hematological malignancies 26% solid tumors 23
Procedure indications N=32 % ACS (UA + NSTEMI) 19 61 STEMI 2 6 New onset CHF 4 12 CP, Abnormal stress test 3 9 PVD,CVA 3 9 Arrhythmia (NSVT) 1 3 24
Thrombocytopenia Definition <150,000.00 MDACC <100,000.00 Platelet Mean = 51.3 x 10 3 /mm 3 (9 91 x 10 3 /mm 3 ) Platelet count distribution 10 9 8 7 6 5 4 3 2 1 0 9 8 8 7 <30,000 30-50 50-70 70-100 <30,000 30-50 50-70 70-100 Interventional Cardiology at MDACC (>50,000.00 = thrombocytosis) 25
Intravascular Access 12 radial 20 femoral Micropuncture kit used in ALL patients 1. Radial approach was preferred, unless: patients had h/o CABG abnormal modified Allen test or abnormal pulse oximetry 2. Femoral approach Aim a little lower Closure device in 5 patients 26
Anticoagulation All patients with stenting and intravascular assessment (IVUS/FFR) were anticoagulated according to current guidelines (ACT>250) All radial cases have received a minimum of 3000 Units of heparin 2 patients have received bivalirudin None of the patients has received/required GPIIbIIIa inhibitors before/during/after the procedure 27
Weight Heparin dose Units/kg Platelet count ACT 103 3000 29 23 279 80 3000 37 9 342 101 3000 30 40 227 54 3000 56 10 348 72 3000 42 49 328 59 4000 68 59 344 81 4500 55 77 346 59 4500 76 60 321 97 5000 60 59 508 78 7000 90 51 550 28
Procedures performed 11 stented (3DES, 8BMS): 3 multivessel stenting 1 LAD CTO (DES) 1 SFA CTO 5 IVUS/FFR 1 angioplasty 15 diagnostic (1 endomyocardial biopsy) 29
Diagnostic cases PL branch 30
Endovascular approach Fractional Flow Reserve (FFR) - intermediate lesions - FFR 0.75 72-year-old gentleman with a longstanding history of MDS bone marrow - progressive disease with 24% blasts (further treatment for his leukemia) Recent NSTEMI, CHF, AS (moderate to severe) and echo with hypokinesis in the LAD territory. Thrombocytopenic (Platelets 15) Radial approach. 31 31
Proximal stenosis 4 months later he continued to be treated for his Acute Myeloid Leukemia with no CV complications NH Pijls J Am Coll Cardiol 2007;49:2105-11. 32
Multivessel stenting 67-year-old Caucasian female diagnosed with ALL in 03/2009. She transferred care to M.D. Anderson Cancer Center April, started on protocol ID 02-230. Her cytogenetics was 46 XX with chromosome 11 abnormality, specifically translocation 4;11. She finished a course of chemotherapy being in remission and currently receiving maintenance therapy. Did not have any donors for a potential transplant. CV heart failure, neck and jaw pain 33
Right coronary artery stenting Subtotally occluded RCA 34
Left anterior descending FFR guided proximal LAD stenting (FFR 0.64 before, 0.85 after) 35
LAD - CTO 65 y.o. male with a history of large B-cell lymphoma treated on protocol liposomal doxorubicin in the rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone (R-CHOP) regimen with intrathecal prophylaxis seen here after attaining clinical remission after finishing seven cycles of chemotherapy Platelets 59,000.00 36
x3 DES in the LAD 37
Medical management Antiplatelet medication N 31 % Aspirin 18 58 Clopidogrel 12 39 (100% stented) ASA & Clopidogrel 8 26 ACE inhibitors 11 36 Beta blockers 26 84 Statins 26 84 38
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Procedural bleeding complications major bleeding (1 patient 3%) was defined as: intracranial, intraocular, or retroperitoneal hemorrhage clinically overt blood loss resulting in a decrease in hemoglobin by >3 g/dl, red cell transfusion of 2 units Post procedure bleeding complications none 40
Postprocedural survival in thrombocytopenic patients 101 100 100 99 98 97 97 96 95 94 94 93 92 91 Procedural Hospitalization 30 Days 2 noncardiac deaths: sepsis and cancer related 41
Conclusions Endovascular procedures can be performed in chronic thrombocytopenic patients Caution: Bleeding from a procedure is more likely due to a procedural problem rather than thrombocytopenia 42