Hematology Data

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Hematology Data. Anemia. Understanding anemia Disease - to be treated on its own merits Condition - a secondary manifestation of another disease Causes Decreased production Blood loss Hemolysis. Classification of Anemia. Acute vs. chronic Signs and symptoms Red cell kinetics - PowerPoint PPT Presentation

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<ul><li><p>Hematology Data</p></li><li><p>AnemiaUnderstanding anemiaDisease - to be treated on its own meritsCondition - a secondary manifestation of another disease</p><p>CausesDecreased productionBlood lossHemolysis</p></li><li><p>Classification of AnemiaAcute vs. chronicSigns and symptoms</p><p>Red cell kineticsDetermined by reticulocyte count</p><p>Red cell sizeDetermined by MCV</p></li><li><p>Laboratory Evaluation of AnemiaComplete blood count</p><p>Reticulocyte count</p><p>Peripheral smear</p></li><li><p>Microcytic Hypochromic Anemia: DiagnosisMild (MCV &gt; 70 fl)Iron deficiency ThalassemiaLead toxicitySideroblastic anemiaAnemia of chronic disease</p></li><li><p>Iron Deficiency AnemiaA world-wide problem3% of toddlers age 1-2 years2-5% of women of child bearing age</p><p>Iron metabolism</p><p>Iron stores</p><p>Laboratory findings of iron deficiency</p><p>Causes of iron deficiency</p><p>Treatment</p></li><li><p>Body Iron Distribution and StorageDietary ironUtilizationUtilizationDuodenum(average, 1 - 2 mgper day)Muscle(myoglobin)(300 mg)Liver(1,000 mg)Bone marrow(300 mg)Circulatingerythrocytes(hemoglobin)(1,800 mg)Reticuloendothelialmacrophages(600 mg)Sloughed mucosal cellsDesquamation/MenstruationOther blood loss(average, 1 - 2 mg per day) StorageironPlasmatransferrin(3 mg)Iron lossMetabolicHemoglobin 1800-2500 mgMyoglobin 300-500 mg</p><p>StorageIron storage 0-1000 mgTransit Serum iron 3 mgTotal 3000-4000 mg</p></li><li><p>Causes of Iron DeficiencyIncreased Utilizationiron requirementsBlood lossGastrointestinal tractGenitourinary tractBlood donationPregnancy and lactation</p><p>Inadequate availabilityiron supplyInsufficient dietary ironImpaired iron absorptionGastric surgeryIntestinal malabsorptionCeliac disease</p></li><li><p>Systemic Manifestations of Iron DeficiencyBehavioral and neuropsychiatric manifestations</p><p>Pica (pagophagia) </p><p>Angular stomatitis</p><p>Glossitis</p><p>Esophageal webs and strictures</p><p>Koilonychia (spooning)</p></li><li><p>Treatment with Oral Iron: General PrinciplesFerrous salts are absorbed better than ferricAll ferrous salts are absorbed to the same extentAscorbic acid increases absorption and toxicityIron is absorbed best on an empty stomachIron should not be given with antacidsIron polysaccharide complex (Niferex) seems to be better tolerated than other iron salts</p></li><li><p>Anemia of Chronic DiseaseAssociated conditionsChronic infection (TB, HIV, osteomyelitis)Chronic inflammatory disorder (rheumatoid arthritis)Neoplasm</p><p>EtiologyImpaired erythropoietin productionImpaired iron utilization from RE systemDirect inhibition of erythropoiesisConsequence of inflammatory cytokines</p></li><li><p>Anemia of Chronic DiseaseCharacteristicsAnemia of variable severity (mild-severe)Low erythropoietin levelLow reticulocyte countWBC and platelet counts are normal</p><p>TreatmentUnderlying conditionErythropoietin</p></li><li><p>Anemia of Chronic Renal DiseaseCharacteristicsWidespread - 8% of US population has increased creatinine23% of patients with chronic renal disease have HCT 30%Long-term anemia is a risk for LVHRisk factor for mortality</p><p>EtiologyInsufficient production of erythropoietin</p></li><li><p>Anemia in Other Clinical ConditionsCondition treated with RBC or ErythropoietinOutcome measured</p><p>Critical care patientsTrend to improved survival</p><p>Elderly patients with Improved 30 day survivalmyocardial infarction</p><p>Congestive heart failureDecreased hospital days</p><p>Cancer and cancer therapyImproved quality of lifeImproved local control with radiation</p></li><li><p>Macrocytic Anemia with Low Reticulocyte CountMegaloblastic anemiaVitamin B12 deficiencyFolate deficiency</p><p>Non-megaloblastic macrocytic anemiaLiver diseaseHypothyroidismDrug-induced (DNA synthesis block)Myelodysplastic syndrome</p></li><li><p>Folate and Cobalamin Daily RequirementsDiet</p><p>Vitamin B12(Cobalamin) Folate</p><p>SourceAnimal productsWidespreadBody stores5 mg5 mgDaily requirement2-5 g50-200 gDaily intake10-20 g400-800 gDietary deficiencyRareCommon</p></li><li><p>Vitamin B12 Deficiency: Common MechanismsIntragastric eventsTotal or partial gastrectomyAbsent intrinsic factor secretionBacterial overgrowthDiphylobothrium latum (fish tapeworm)Disease of the terminal ileum</p></li><li><p>Pernicious AnemiaMost common cause of vitamin B12 deficiencyAssociated with-autoimmune diseasesScreen for thyroid disease every 1-2 yearsPernicious anemia is a systemic diseaseGastrointestinal tract involvementNeurologic involvement</p></li><li><p>Pernicious Anemia: Laboratory DiagnosisAnti-intrinsic factor antibodiesAnti-parietal cell antibodiesSchilling testProcedureAbsorption of radiolabeled cobalamin Intrinsic factorMeasure urinary excretion of radioactivity</p></li><li><p>Treatment of Vitamin B12 DeficiencyParenteral cobalamin1 mg/day x 7 days1 mg/week x 4 weeks1 mg/month for life</p><p>Oral cobalamin1 mg/day for life</p></li><li><p>Tongue in B12 Deficiency </p></li><li><p>Folate (Vitamin B9) DeficiencyMinimum daily folate requirement is 50 gUsual dietary folate 50-500 gAbsorption in upper small intestineCauses of folate deficiency- Dietary (90%)Alcohol abusePregnancyMalabsorptionDrug-inducedTreatment - oral folic acid supplementation</p></li><li><p>Glucose-6-Phosphate Dehydrogenase DeficiencyG-6-PD: reduces NADP/oxidizes glucose-6-phosphateDetoxifies free radicals and peroxidesSex-linked disorderEffects &gt; 200 million peopleHemolytic anemia occurs in the presence of stress (infection or drugs)African form - mild hemolysisMediterranean form - more severeUnique sensitivity to fava beans</p></li><li><p>Acute Leukemia</p></li><li><p>OverviewConcepts, biologyEpidemiologyClinical and laboratory manifestationsDiagnosisManagement and prognosis</p></li><li><p>Classification of leukemiasAcuteChronicMyeloid originLymphoid originAcute Myeloid Leukemia (AML)Acute Lymphoblastic Leukemia (ALL)Chronic Myeloid Leukemia (CML)Chronic Lymphocytic Leukemia (CLL)</p></li><li><p>Acute Leukemiaaccumulation of blasts in the marrow</p></li><li><p>Significance of adult acute leukemiaa hematologic urgencyusually fatal within weeks to months without chemotherapywith treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia)notify Hematologist promptly if acute leukemia is suspected</p></li><li><p>Classification of acute leukemiasALLmainly childrenM &gt; Fcurable in 70% of childrencurable in minority of adultsAMLmainly adultsM &gt; F</p><p>curable in minority of adults</p></li><li><p>Causes of acute leukemiasidiopathic (most)underlying hematologic disorderschemicals, drugsionizing radiationviruses (HTLV I)hereditary/genetic conditions</p></li><li><p>Clincal manifestationssymptoms due to:marrow failuretissue infiltrationleukostasisconstitutional symptomsother (DIC)usually short duration of symptoms</p></li><li><p>Marrow failureneutropenia: infections, sepsisanemia: fatigue, pallorthrombocytopenia: bleeding</p></li><li><p>Infiltration of tissues/organsenlargement of liver, spleen, lymph nodesgum hypertrophybone painother organs: CNS, skin, testis, any organ</p></li><li><p>Gum hypertrophy</p></li><li><p>Leukostasisaccumulation of blasts in microcirculation with impaired perfusion lungs: hypoxemia, pulmonary infiltratesCNS: strokeonly seen with WBC &gt;&gt; 50 x 109/L</p></li><li><p>Constitutional symptomsfever and sweats commonweight loss less common</p></li><li><p>Laboratory featuresWBC usually elevated, but can be normal or lowblasts in peripheral bloodnormocytic anemiathrombocytopenianeutropeniaDIC</p></li><li><p>Bone marrow in acute leukemianecessary for diagnosisuseful for determining typeuseful for prognosisAcute leukemias are defined by the presence of &gt; 20% blasts in bone marrow (% of nucleated marrow cells)</p></li><li><p>Treatment of acute leukemiasChoice of Rx is influenced by:type (AML vs ALL)agecurative vs palliative intent</p></li><li><p>Principles of treatmentcombination chemotherapyfirst goal is complete remissionfurther Rx to prevent relapsesupportive medical caretransfusions, antibiotics, nutritionpsychosocial supportpatient and family</p></li><li><p>Hematopoietic stem cell transplantationpermits rescue from otherwise excessively toxic treatmentadditional advantage of graft-vs-leukemia effect in allogeneic transplantstrade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic</p></li><li><p>LYMPHOID DISORDERS</p></li><li><p>Topics to be CoveredNon-Hodgkins LymphomaHodgkins DiseaseMultiple Myeloma</p></li><li><p>Lymphoma and Multiple Myeloma2004 U.S. Predicted ValuesMalignancyNew CasesDeaths</p><p>All Cancers 1,368,030 563,700Non-Hodgkins Lymphoma 54,37019,410Hodgkins Disease7,880 1,320Multiple Myeloma 15,270 11,070CA Cancer J Clin 2004; 54:8-29</p></li><li><p>Non-Hodgkins Lymphoma</p></li><li><p>Non-Hodgkins Lymphoma (NHL)6th most common cause of cancer death in United States.Increasing in incidence and mortality.Since 1970, the incidence of lymphoma has almost doubled.</p></li><li><p>Types of LymphomaIndolent (low grade)Life expectancy in years, untreated85-90% present in Stage III or IVIncurableIntermediateAggressive (high grade)Life expectancy in weeks, untreatedPotentially curable</p></li><li><p>Etiology of NHLImmune suppressioncongenital (Wiskott-Aldrich)organ transplant(cyclosporine)AIDSincreasing ageDNA repair defectsataxia telangiectasiaxeroderma pigmentosum</p></li><li><p>Etiology of NHLChronic inflammation and antigenic stimulationHelicobacter pylori inflammation, stomachChlamydia psittaci inflammation, ocular tissuesSjgrens syndromeViral causes-EBV and Burkitts lymphomaHTLV-I and T cell leukemia-lymphomaHTLV-V and cutaneous T cell lymphomaHepatitis C</p></li><li><p>Clinical FeaturesLymphadenopathyCytopeniasSystemic symptomsHepatosplenomegalyFeverNight sweats</p></li><li><p>Clinical FeaturesLymphadenopathy may fluctuate or spontaneously remit, especially in low-grade lymphomas.Body symptoms more common in high-grade lymphomas.Hematogenous spread of disease, with no predictable pattern.</p></li><li><p>Clinical FeaturesClassic lymphoma: arises in lymph node or bone marrow.Extranodal primary more common in high-grade lymphoma.Waldeyers ring involvement frequent in GI lymphomas.</p></li><li><p>Diagnosis of NHLChromosome changes14;18 translocation in follicular lymphomabcl-2 oncogenet(8;14), t(2;8), t(8;22) in Burkitts lymphoma c-myc oncogenet(11;14) in mantle cell lymphomacyclin D1 gene</p></li><li><p>Staging WorkupCBC, chemistries, urinalysisCT scans of chest, abdomen and pelvisBone marrow biopsy and aspirate(Lumbar puncture)AIDS lymphomaT cell lymphoblastic lymphomaHigh grade lymphoma with positive marrow</p></li><li><p>Treatment Options:Indolent lymphomas</p><p>10-15% in Stage I or IIpotentially curablelocal radiotherapy85-90% Stage III or IVincurabletreatment does not prolong survival</p></li><li><p>CHOP ChemotherapyCyclophosphamide (Cytoxan)Hydroxydaunorubicin (Adriamycin)Oncovin (vincristine)Prednisone</p></li><li><p>Burkitts LymphomaAfrican variety: jaw tumor, strongly linked to Epstein-Barr Virus infection.In U.S., about 50% EBV infection.May present as abdominal mass.Most rapidly growing human tumor.Typical chromosome abnormality: c-myc oncogene linked to one of the immunoglobulin genes.</p></li><li><p>Burkitts Lymphoma</p><p>Treated with multidrug regimen similar to pediatric leukemia/lymphoma regimens.</p></li><li><p>AIDS LymphomaAggressive lymphomas of B cell origin.Burkitts, Burkitts-like, and large cell immunoblastic.Treatment often limited by immune compromise of the patient.Prognosis improved with HAART therapy.</p></li><li><p>MALT LymphomaMucosa-Associated Lymphoid TissueChronic infection of the stomach by Helicobacter pylori.Localized to the stomach, indolent course.Can be cured in many cases by antibiotics against H. pylori.</p></li><li><p>Thomas HodgkinEnglish pathologist, described the disease that bears his name in 1832.Hodgkins Disease</p></li><li><p>Hodgkins DiseaseOne-seventh as common as non-Hodgkins lymphoma.Highly treatable and curable, even when disseminated.Presence of Reed-Sternberg cell is necessary to make diagnosis.</p></li><li><p>Reed-Sternberg Cell</p></li><li><p>EpidemiologyIn developed countries, bimodal distribution of patients.young adulthoodafter age 50More common in affluent families with few siblings.In developing countries, more common in young children.</p></li><li><p>Signs and SymptomsLymph node enlargement, usually cervical or mediastinal.Systemic B symptoms common.Pel-Ebstein fever.Relapsing, high-grade fever that can reach 105-106F, periodicity of 7-10 days. Fever spikes abrupt in onset and resolutionPain on drinking alcohol.</p></li><li><p>Clinical FeaturesT cell mediated immune deficiency, even in early stage disease. Prone to infections:Herpes zoster (shingles) in one fourth of patientsFungal or mycobacterial infectionsImmune defect may persist even after lymphoma is cured.</p></li><li><p>Clinical FeaturesPredictable contiguous spread of disease:cervical nodes to mediastinum or axillamediastinum to periaortic nodes or spleen, etc.Basis for staging and treatment decisions.</p></li><li><p>DiagnosisExcisional biopsy of a lymph node.</p><p>Fine needle aspirate is not sufficient to make the diagnosis of Hodgkins disease.</p></li><li><p>Staging of Hodgkins DiseaseSame as for non-Hodgkins: H + P, labs, CT scans, bone marrow biopsyPLUS:Gallium scanLymphangiogram or staging laparotomy ONLY if results would affect treatment decisions</p></li><li><p> Treatment by Stage</p><p>Stage</p><p>Therapy</p><p>% Cure</p><p> IA</p><p> XRT</p><p>95</p><p> IIA</p><p> XRT</p><p>85</p><p> IB, IIB</p><p> XRT (Total Nodal)</p><p>70</p><p> IIIA</p><p> XRT</p><p>70</p><p> IIIB, IV</p><p> Combination Chemo</p><p>50</p></li><li><p>Chemotherapy RegimensMOPPMechlorethamine, Oncovin, Procarbazine, PrednisoneABVDAdriamycin, Bleomycin, Vinblastine, DacarbazineBEACOPP</p></li><li><p>Treatment OptionsOften, patients who relapse after radiotherapy can be cured by salvage chemotherapy.Combined chemotherapy and radiotherapy is given for bulky mediastinal masses.Chemotherapy now being tested for earlier stages of the disease.</p></li><li><p>Late Complications ofHodgkins DiseaseHigh incidence of second malignanciesleukemia first 10 years, solid tumors over time.Leukemia in patients receiving alkylating agents or combined chemo/XRT.Lung cancer and breast cancer in patients receiving XRT to chest. Lung cancer especially high in smokers.</p></li><li><p>Late Complications ofHodgkins DiseaseHypothyroidism after irradiation of the neck.Constrictive pericarditis after radiotherapy to the mediastinum.Infertility after use of alkylating agents.Heart failure after Adriamycin treatment.</p></li><li><p>Multiple Myeloma</p></li><li><p>Overview of Multiple MyelomaLess common than non-Hodgkins lymphoma, more deadly. Average life expectancy 30 -36 months. Some patients develop a very indolent form and live for 10 years or more.Potentially curable with high dose chemotherapy (bone marrow or stem cell transplantation).</p></li><li><p>Overview of Multiple MyelomaDisease of malignant B-lymphocytes.Little similarity to lymphoma in presentation, age at diagnosis, treatment, or prognosis.Signs and symptoms of multiple myeloma are quite variable. Approximately 20% of patients have no symptoms.</p></li><li><p>Etiology of Multiple MyelomaUnknown. Suggested predisposing factors include:Viral infection with Human Herpesvirus 8 (HHV-8).MGUS (monoclonal gammopathy of undetermined significance).</p></li><li><p>EpidemiologyAverage age at presentation is about 65.Males are affected more often than females.Incidence in blacks is twice that of whites.Five-year survival is approximately 25-30%.Median survival 30-36 months.</p></li><li><p>Multiple MyelomaMore than 15% plasma cells in the bone marrow.Monoclonal immunoglobulin peak on SPEP more than 3 gm/dL.Presence of Bence Jones protein in urine.Decreased levels of normal immunoglobulins.</p></li><li><p>Clinical FeaturesBone marrow failure - Anemia, thrombocytopenia, neutropeniaRenal failure Bone disease with skeletal destructionlytic lesionsgeneralized decrease in bone densityHypercalcemia</p></li><li><p>Clinical FeaturesHyperviscosity syndromeRecurrent infectionsAmyloidosis</p></li><li><p>Diagnosis and Staging WorkupBone marrow biopsy and aspirateSerum protein electrophoresis and immunofixationSkeletal surveyPlain x-rays are better than bone scan.Lytic lesions d...</p></li></ul>