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HEME/ONC - Coggle Diagram

- - - - erythrocytes
      - thrombocytes
      - neutrophils
      - macrophages
    - - plasma cell
      - memory B-cells
      - T lymphocyte
  - - - proliferative disorder of the bone marrow with prominent erythroid proliferation
      - males >40 yo
      - SOB, splenomegaly, headache, pruritis, redness of skin
      - treatment: phlebotomy, Hydrea or Interferon
      - complications: acute thrombotic event, transformation to acute myeloid leukemia or primary meylofibrosis
    - - clonal proliferation of hematopoietic progenitor cell; colonization of extramedullary sites (spleen, liver)
      - leukocytosis, normocellular/hypocellular bone mare with marked fibrosis, splenomegaly
      - treatment: observation/supportive care, splenectomy, chemotherapy (JAK2 inhibitors), stem cell transplant
    - - chronic myeloproliferative disorder with increased megakaryocyte production and associated sustained, unexplained thrombocytosis
      - platelet count >600,000, megakaryocyte hyperplasia, splenomegaly, thrombotic/hemorrhagic events
      - treatment: observation; platelet reduction with Hydrea, anagrelide or pheresis in thrombotic emergency
- - - - heme produced in cell mitochondria
      - globin produced in polyribosomes in cell
      - requirements: adequate iron delivery & supply, protoporphyrin synthesis, globulin synthesis
  - - - Primary
        
        hemochromatosis
        
        5 types (type 3 results in fetal death)
        
        severe fatigue, impotence, arthralgia, 75% asymptomatic
        
        hepatomegaly, cardiomegaly, skin bronzing or hyperpigmentation
        
        labs: iron high, transferrin saturation >45%, ferritin high, TIBC low, UIBC low
        
        liver biopsy, MRI, SQUID, liver iron concentration
        
        management: early recognition, therapeutic phlebotomy, iron chelation
        
        ceruloplasminemia
        
        atransferrinanemia
      - Secondary
        
        hemaglobinopathies
        
        sideroblastic anemia
        
        defect limits iron uptake into heme
        
        failure to form heme molecule
        
        increased iron deposits in cell mitochondria and bone marrow which forms a ring
        
        primary & acquired
        
        fatigue, dizziness, pale skin, enlarged spleen & liver
        
        labs: serum iron normal/high, transferrin saturation high, ferritin high, TIBC normal/low, UIBC low/normal, hematocrit 20-30%, MCV low
        
        can cause microcytic hypochromic anemia
        
        management: remove toxic agent, administer pyridoxin, thiamine & folate; blood transfusion or bone marrow transplant; chelation with IV Deferioxamine followed by oral Deferiprone
        
        thalassemia
        
        quantitative defect of globulin chain synthesis
        
        ALPHA: genes related to alpha globin protein missing or changed (chromosome 16); persons of African or southeast Asian descent
        
        BETA: gene defects affect beta globin protein (chromosome 11); persons of Mediterranean origin
        
        major -- inherit defect gene from both parents
        
        minor -- defect gene inherited from one parent
        
        fatigue, malnourished, SOB, jaundice, facial bone deformities, enlarged spleen
        
        labs: CBC shows anemia, smear shows small abnormally shaped RBCs, hemoglobin electrophoresis shows abnormal hemoglobin form
        
        management: lifelong transfusions, folic acid, splenectomy >5yo, chelation therapy, stem cell transplant
        
        causes severe anemia in first year of life
        
        porphyria
        
        defect in heme synthesis
        
        sickle cell
        
        qualitative defect of globulin chain synthesis
        
        autosomal recessive genetic blood disorder
        
        RBCs assume an abnormal, rigid sickle shape
        
        disease (inherited from both parents) vs. trait (inherited from only one parent)
        
        complications: vaso-occlusive crises, splenic sequestration crises, strokes, osteomyelitis, aplastic crisis (sudden drop in hemoglobin), acute chest syndrome (vaso-occlusive crisis in pulmonary vasculature)
        
        dizziness, SOB, fatigue, pain in chest, arms & legs, swelling of fingers & toes in infants & young children
        
        management: transfusion therapy
        
        chronic transfusion
        
        chronic excess ingestion
      - sequelae: cardiac failure, liver cirrhosis/fibrosis/cancer, diabetes mellitus, infertility, growth failure
    - - blood loss
      - increased iron usage
      - malabsorption
      - dietary inadequacy
      - combinations
      - normocytic anemias:
        
        anemia of chronic disease
        
        iron reuse defect
        
        blunted erythropoietin secretion or responsiveness
        
        mild shortening of RBC survival
        
        direct marrow suppression by cytokines
        
        causes: inflammatory disorders (RA, lupus erythematosus, IBD), chronic infections (TB, osteomyelitis, endocarditis), malignancies (lymphoma, renal cell cancer)
        
        management: determine underlying cause and treat
        
        anemia of renal disease
        
        hypoplastic anemia
        
        form of aplastic anemia due to a congenital disorder characterized by a decreased production of RBCs and defective function of the blood-forming organs caused by toxic agents (i.e. chemicals, xrays)
        
        myelophthistic anemia
        
        release of immature red cells into circulation
        
        mild iron deficiency
      - microcytic anemias:
        
        hypochromic, microcytic
        
        iron deficiency anemia
        
        extreme fatigue or weakness, SOB, headache, dizziness/lightheadedness, cold hands/feet, limb paresthesias, pica, poor appetite (in children), tachycardia, pallor, brittle nails, angular keilosis
        
        delayed growth, frontal bossing, skin pallor, jaundice, splenomegaly, signs of systemic infection
        
        treatment: oral iron
        
        thalassemia minor
        
        anemia of chronic disease
        
        hereditary sideroblastic anemia
        
        lead poisoning
        
        causes: GI bleeding, chronic gross hematuria, chronic hemoptysis, malabsorption, post-gastrectomy, intravascular hemolysis
- - - - sickle cell
        
        symptoms develop after first few months of life
        
        sickle cells that become noncompliant in hypoxic states
        
        autosomal recessive
        
        therapy: penicillin prophylaxis, routine immunizations + meningococcal & pneumococcal, splenectomy, avoid high risk activities (high altitude, weather extremes, dehydration), NSAIDs, monthly blood transfusions, Hydroxyurea, stem cell transplant
      - thalassemia
        
        alpha subtypes
        
        silent carrier (one gene deleted) --> no clinical or laboratory consequences
        
        alpha thalassemia trait (two genes deleted, 50%) --> mild, microcytic anemia; not clinically significant
        
        hemoglobin H disease (3 genes deleted) --> more severe microcytic anemia, +/- transfusion needs
        
        alpha thalassemia major (4 genes deleted) --> hydrops fetalis
        
        beta subtypes
        
        beta thalassemia intermedia (some production on two genes) --> variable disease severity, asymptomatic to chronic transfusions
        
        beta thalassemia minor (one gene with some/no production) --> usually asymptomatic and mildly anemic
        
        beta thalassemia major (two no production genes) --> life-long transfusion-dependent anemia, hepatosplenomegaly, and skeletal deformities
        
        treatment: transfusion, splenectomy, stem cell transplant (curative)
    - - spherocytosis
        
        genetic mutation causing sphering of the RBC
        
        anemia, reticulocytosis, increased bilirubin +/- increased LDH
        
        splenomegaly, gallstones
      - paroxysmal nocturnal hemoglobinuria (PNH)
        
        acquired PIGA mutation
        
        bright red urine in the morning
        
        hemolytic anemia + thrombosis
        
        requires transfusion if acute hematologic instability; treat with Eculizumab infusions; can progress to bone marrow failure which requires stem cell transplant
        
        rare cause of iron deficiency
    - - G6PD deficiency
        
        RBCs are at an increased risk of hemolysis after oxidative stress (infection, sulfa drugs, fava beans, moth balls)
        
        African, Mediterranean, Middle East descent
        
        treatment: removal of offending agent
      - pyruvate kinase deficiency
        
        alters deoxygenation of hemoglobin in a positive manner
        
        treated with transfusion +/- splenectomy
  - - - warm
        
        IgG anti-RBC antibodies coat the RBC and act as opsonins, react at body temperature
        
        most common AIHA
        
        treatment: steroids and transfusion +/- immune suppression
        
        Coombs Test = positive IgG or C3d
      - cold
        
        IgM antibodies agglutinate RBCs at temperatures below core body temperature
        
        often seen with mycoplasma pneumonia, hep A, and infectious mono
        
        Coombs test = positive C3 and negative IgG
        
        treatment: warmth, steroids, occasionally plasmapheresis
        
        cold agglutinin disease (CAD) = a chronic relapsing type of AIHA
    - - march hemoglobinuria, prosthetic valvular trauma, thrombectomy, abrupt osmolality changes, heat denaturation
- - - - radiation may be considered for lymphoma or head/neck tumors
      - rarely chemotherapy
      - surgery is mainstay
- - - - diagnostics: CBC, CMP, LDH, uric acid, HIV, hepatitis panel, CT of chest, abdomen, pelvis and neck or PET-CT, excisional LNbiopsy, bone marrow biopsy, neurological assessment, transthoracic echocardiogram
      - Ann Arbor Staging System
      - treatment (indolent): observation may be appropriate, radiation
      - treatment (aggressive): R-CHOP +/- radiation
      - supportive care: beware of tumor lysis syndrome & prophylax; prophylactic antibiotics for infections
      - other considerations: CNS disease, spinal cord compression
    - - painless lymphadenopathy (frequently cervical or supraclavicular)
      - B symptoms in ~25% of pts
      - more than 50% of pts have a mediastinal mass which can be asymptomatic or present as dyspnea, cough or obstruction of SVC
      - marrow involvement <10%
      - Ann Arbor Staging System
      - diagnostics: CBC, CMP, LDH, uric acid, HIV, hepatitis panel, CT scan of chest, abdomen, pelvis and neck or PET-CT, excisional LN biopsy, bone marrow biopsy, PFTs, transthoracic echocardiogram
      - treatment (early): ABVD + RT
      - treatment (advanced): ABVD, AVD + Brentuximab
- - - - causes: gastric abnormalities (pernicious anemia, resection, gastritis, H. pylori), small bowel disease (ileal resection, Crohn's), pancreatitis, diet (vegans, malnourished, alcoholics), agents that block absorption (neomycin, biguanides, PPIs, N20 anesthesia), inherited transcobalamin II deficiency, competition syndrome (bacterial overgrowths, tapeworm)
      - macrocytic anemia, thrombocytopenia, neutropenia, hypersegmented neutrophils, weight loss, N/V, glossitis, subacute combined degeneration of the spinal cord (SCDSC), dementia, depression, elevated MMA +/- homocysteine, low serum B12, increased LDH
      - treatment: IM injections monthly, 1-2mg PO daily, 1 spray intranasal daily
    - - causes: inadequate diet (alcoholics, lack of foliage), malabsorption disorder (celiac disease, IBD), iatrogenic malabsorption (methotrexate, trimethoprim, ethanol, phenytoin), increased folate requirements (pregnancy)
      - 1-5mg PO daily
    - - autoimmune disease with antibodies against gastric parietal cells; anti-IF antibodies