Anemia In Cancer Patients

He ANEMIA IN CANCER PATIENTS Dr. Leiva ANEMIA IN CANCER Anemia present in 30-90% of cancer patients Classified into 3 categories: ­ Decreased production of RBCs ­ Increased destruction of RBCs ­ Blood loss Correction achieved by either: ­ Treating underlying etiology or ­ Providing supportive care ­ Packed Red Blood Cells (PRBC) or Erythropoiesis-stimulating agents (ESAs) w/ or w/out iron supplementation ETIOLOGY - COMPLEX AND MULTIFACTORIAL Anemia due to: ­ Bleeding ­ Hemolysis 3 ­ Renal insufficiency a ­ Nutritional deficiencies ­ Cancer cellsS SW 6­ Suppress hematopoiesis I­ CytokinesIron sequestration 8­ Radiation in a ­ Chemotherapy!!! PATHOPHYSIOLOGY E O CHEMOTHERAPY INDUCED ANEMIA Chemotherapy: ­ Impairs hematopoiesis ­ Synthesis of RBC precursors in bone marrow ­ Alkylating agents, Docetaxel/Cabazitaxel, Topotecan ­ Platinum based regimens ­ Nephrotoxic effects (Cisplatin) ­ Decreased production of erythropoietin in kidney CHEMOTHERAPY INDUCED ANEMIA  Myelosuppressive effects accumulate over time  Erythrocyte lifespan 90 -120 days  detection of treatmentassociated anemia may not manifest for 4–6 weeks following receipt of myelosuppressive therapy  Consideration of the agent helps predict severity  Time to nadir level can vary (often ~ 2 weeks) ANEMIA SCALE PER NATIONAL CANCER INSTITUTE <6.5 EVALUATION OF ANEMIA IN CANCER PATIENTS AW APPROACHES TO ANEMIA EVALUATION 2 Common methods to evaluating anemia (Need Both) ­ Morphologic ­ MCV or average RBC size 2 ­ Kinetic ­ Underlying cause; production, destruction, or RBC loss MORPHOLOGIC Microcytic (<80 fL) • • • • Iron deficiency Thalassemia, Anemia of chronic diseases Sideroblastic anemia Macrocytic (>100 fL) • Medications and alcoholism (both non-megablastic anemias) • Myelodysplastic Syndrome (MDS) • Macrocytosis in megablastic anemia most often vitamin deficiencies (lack of folic acid or B12) or antibodies to parietal cells • Macrocytosis + increased reticulocyte counts follow brisk hemorrhage or hemolysis Normocytic (80 – 100 fL) • • • • • Hemorrhage Hemolysis Bone marrow failure Anemia of chronic inflammation Renal insufficiency thatarereleased Reticulocytes soimmatureRBC cerythrocytes nowtoBloodstreamd fromboheme KINETIC Focuses on underlying reasons ­ Can tell you if problem is production, destruction, or loss of RBCs. ­ Reticulocyte count is usually a % ­ Reflects # of immature RBCs/per Total RBCs RI calculated based on reticulocyte count  indicates RBC production capacity by the bone marrow Reticulocytes circulation for 24 hours before becoming erythrocytes, but as anemia increases younger retics are released from marrow and give a falsely high RI value Reticulocyte production index (RPI) adjusts for this ­ Low RI/RPI ratio (<1) – decreased RBC production, Fe deficiency, B12/Folate deficiency, or chemo/cancer related bone marrow disfunction ­ High RI/RPI ratio (>1) - normal RBC production therefore blood loss or hemolysis in the anemic patient RISK ASSESSMENT FOR INITIAL TRANSFUSION Watch and Wait *Most Likely We will Give RBCs *We will Give RBCs!!!! Hst ormeasure t ofRBC PRBC TRANSFUSIONS  Transfusion of 1 unit (300 cc) of PRBCs results in an average increase in Hb level by 1g/dL OR increased Hct level by 3% in an adult who is not also experiencing blood loss  Studies have shown an increase in overall survival when patients either started therapy with high Hb levels or received transfusions to increase Hb  Study done 1995-2003 Increase in VTE events and decreased survival, which may be a result of advanced cancer and not transfusions. WHAT HAPPENS WHEN PATIENTS REFUSE BLOOD PRODUCTS? ***DON’T PANIC!!!!  Limited data on best management for patients who refuse  Extreme cases of life-threatening anemia, pure O2 (400 mg Hg, SaO2 =1.0) by mechanical ventilation used to increase oxygenation  Reduce blood loss – minimize phlebotomy, use pediatric tubes, return discard in closed system, batch test Prior to myelosuppressive chemo  Consider anemia risk when deciding treatment  Consider daily folicBe acid and B12 supplementation  Evaluate and correct baseline coagulation abnormalities  Use IV iron in patients with high suspicion of folate and B12 deficiencies  Consider ESAs for selected patients by FDA dosing/dosing adjustments  ESAs will be prescribed off-label Blood substitutes  Clinicians can obtain access to investigational blood substitute products for a single patient through Expanded Access through the FDA ESA VS. TRANSFUSION ESA in the Cancer Setting RBC Transfusion Risks • Increased thrombotic events • Possible decreased survival • Time to tumor progression shortened Angiogenesis • Transfusion reactions (eg, hemolytic, lung injury) • Transfusion-associated circulatory overload (TACO) • Virus transmission (eg. Hepatitis, HIV) • Bacterial contamination • Iron overload • Increased thrombotic events • Possible decreased survival • Alloimmunization • Increased risk of poor response to future platelet transfusions due to HLA immunization Goals • Transfusion avoidance • Gradual improvement in anemia-related symptoms • Rapid increase of Hb and hematocrit levels • Rapid improvement in anemia-related symptoms e O O SPECIAL CATEGORIES IN CONSIDERING ESA USE eyed i ESA DRUGS Epoetin alpha (Procrit, Epogen), Epoetin alpha-epbx (Retacrit) and Darbepoetin alpha (Aransep®) ­ MOA: ­ Regulates production of red blood cells by stimulating division and differentiation of committed erythroid progenitor cells in the bone marrow ­ According to PI: Initiate ONLY if Hb <10 g/dL and anticipated duration of myelosuppressive chemotherapy is at least 2 additional months. ­ Titrate dosage to use the minimum effective dose that will maintain a Hb level sufficient to avoid RBC transfusions ­ ADRs: ­ Generally when targeting Hb >11 g/dL ­ Cardiovascular events (HTN, VTE, MI) ­ Cancer progression and decreased survival Must know the info in the red boxes! ESA DOSING AND TITRATION Exon IRON DEFICIENCY usuallygiveduinn BCI of Giproblems y constipation NOIM PARENTERAL IRON PREPARATIONS WRAP UP Common problem • 30-90% of cancer patients experience anemia Etiology of Anemia in cancer patients • Decreased production of RBCs • Increased destruction of RBCs • Blood loss Defining anemia • Hb <11g/dL OR Drop of >2g/dL from baseline Evaluation of anemia in cancer patients • Morphologic • Kinetic Treatment Considerations and Risks • Transfusions • ESAs • Parenteral iron