RBC and BLEEDING DISORDERS www.freelivedoctor.com
RBC and Bleeding Disorders <ul><li>NORMAL </li></ul><ul><ul><li>Anatomy, histology </li></ul></ul><ul><ul><li>Development ...
www.freelivedoctor.com Classical RBC’s and platelets,
www.freelivedoctor.com Classical features of peripheral white cells
www.freelivedoctor.com Adult Reference Ranges for Red Blood Cells     Measurement (units) Men Women Hemoglobin (gm/dL) 13....
www.freelivedoctor.com Bone marrow biopsy stained with H&E (left), and smear stained with Giemsa (right).
WHERE is MARROW? <ul><li>Yolk Sac: very early embryo </li></ul><ul><li>Liver, Spleen: NEWBORN </li></ul><ul><li>BONE </li>...
MARROW FEATURES <ul><li>CELLULARITY </li></ul><ul><li>MEGAKARYOCYTES </li></ul><ul><li>M:E RATIO </li></ul><ul><li>MYELOID...
MARROW “ DIFFERENTIATION” www.freelivedoctor.com
www.freelivedoctor.com
ANEMIAS* <ul><li>BLOOD LOSS </li></ul><ul><ul><li>ACUTE </li></ul></ul><ul><ul><li>CHRONIC </li></ul></ul><ul><li>IN-creas...
Features   of ALL anemias <ul><li>Pallor, where? </li></ul><ul><li>Tiredness </li></ul><ul><li>Weakness </li></ul><ul><li>...
www.freelivedoctor.com Blood Loss Acute: trauma Chronic: lesions of gastrointestinal tract, gynecologic disturbances. The ...
HEMOLYTIC <ul><li>HEREDITARY </li></ul><ul><ul><li>MEMBRANE disorders: e.g., spherocytosis </li></ul></ul><ul><ul><li>ENZY...
IMPAIRED PRODUCTION <ul><li>Disturbance of proliferation and differentiation of stem cells: aplastic anemias, pure RBC apl...
MODIFIERS <ul><li>MCV, microcytosis, macrocytosis </li></ul><ul><li>MCH  </li></ul><ul><li>MCHC, hypochromic </li></ul><ul...
HEMOLYTIC ANEMIAS <ul><li>Life span LESS than 120 days </li></ul><ul><li>Marrow hyperplasia (M:E), EPO+ </li></ul><ul><li>...
HEMOLYSIS <ul><li>INTRA-vascular (vessels) </li></ul><ul><li>EXTRA-vascular (spleen) </li></ul>www.freelivedoctor.com
HEREDITARY SPHEROCYTOSIS Genetic defects affecting ankyrin, spectrin, usually autosomal dominant Children, adults Anemia, ...
Glucose-6-Phosphate  Dehydrogenase (G6PD) Deficiency <ul><li>A -   and Mediterranean are most significant types </li></ul>...
FEATURES of G6PD Defic. <ul><li>Genetic: Recessive, X-linked </li></ul><ul><li>Can be triggered by foods (fava beans), oxi...
Sickle Cell Disease <ul><li>Classic hemoglobinopathy </li></ul><ul><li>Normal HGB is  α 2  β 2:  β -chain defects (Val->Gl...
Clinical features of HGB-S disease <ul><li>Severe anemia </li></ul><ul><li>Jaundice </li></ul><ul><li>PAIN (pain CRISIS) <...
www.freelivedoctor.com
THALASSEMIAS <ul><li>A WIDE VARIETY of diseases involving GLOBIN synthesis, COMPLEX genetics </li></ul><ul><li>Alpha  or  ...
Hemoglobin H Disease <ul><li>Deletion of THREE alpha chain genes </li></ul><ul><li>HGB-H is primarilly Asian </li></ul><ul...
HYDROPS FETALIS <ul><li>FOUR alpha chain genes are deleted, so this is the MOST SEVERE form of thalassemia </li></ul><ul><...
Paroxysmal Nocturnal Hemoglobinuria  (PNH) <ul><li>ACQUIRED, NOT INHERITED like all the previous hemolytic anemias were </...
Immunohemolytic Anemia <ul><li>All of these have the presence of antibodies and/or compliment present on RBC surfaces </li...
IMMUNOHEMOLYTIC ANEMIAS <ul><li>WARM  (IgG), will NOT hemolyze at room temp </li></ul><ul><ul><li>Primary Idiopathic (most...
COOMBS TEST <ul><li>DIRECT: Patient’s CELLS are tested for surface Ab’s </li></ul><ul><li>INDIRECT: Patient’s SERUM is tes...
HEMOLYSIS/HEMOLYTIC ANEMIAS DUE TO RBC TRAUMA <ul><li>Mechanical heart valves breaking RBC’s </li></ul><ul><li>MICROANGIOP...
NON-Hemolytic Anemias: i.e., DE-creased Production <ul><li>“ Megaloblastic” Anemias </li></ul><ul><li>B12 Deficiency (Pern...
MEGALOBLASTIC ANEMIAS <ul><li>Differentiating megaloblasts (marrow) from macrocytes (peripheral smear, MCV>94) </li></ul><...
www.freelivedoctor.com Decreased intake Inadequate diet, vegetarianism Impaired absorption Intrinsic factor deficiency    ...
Vit-B12 Physiology <ul><li>Oral ingestion </li></ul><ul><li>Combines with INTRINSIC FACTOR in the gastric mucosa </li></ul...
Please remember that ALL megaloblastic anemias are also MACROCYTIC (MCV>94  or  MCV~100), and that not only are the RBC’s ...
PERNICIOUS ANEMIA <ul><li>MEGALOBLASTIC anemia </li></ul><ul><li>LEUKOPENIA and HYPERSEGS </li></ul><ul><li>JAUNDICE </li>...
FOLATE DEFICIENCY MEGALOBLASTIC AMEMIAS <ul><li>Decreased Intake: diet, etoh-ism, infancy </li></ul><ul><li>Impaired Absor...
Fe Deficiency Anemia <ul><li>Due to increased loss or decreased ingestion, almost always, in USA, nowadays, increased loss...
Fe Transferrin Ferritin (GREAT test) Hemosiderin www.freelivedoctor.com
Clinical Fe-Defic-Anemia <ul><li>Adult men: GI Blood Loss </li></ul><ul><li>PRE menopausal women: menorrhagia </li></ul><u...
www.freelivedoctor.com
2 BEST lab tests: <ul><li>Serum Ferritin </li></ul><ul><li>Prussian blue hemosiderin stain of marrow (also called an “iron...
Anemia of Chronic Disease <ul><li>CHRONIC INFECTIONS </li></ul><ul><li>CHRONIC IMMUNE DISORDERS </li></ul><ul><li>NEOPLASM...
APLASTIC ANEMIAS <ul><li>ALMOST ALWAYS involve platelet and WBC suppression as well </li></ul><ul><li>Some are idiopathic,...
APLASTIC ANEMIAS www.freelivedoctor.com
APLASTIC ANEMIAS <ul><li>CHLORAMPHENICOL </li></ul><ul><li>OTHER ANTIBIOTICS </li></ul><ul><li>CHEMO </li></ul><ul><li>INS...
MYELOPHTHISIC  ANEMIAS <ul><li>Are anemias caused by metastatic tumor cells replacing the bone marrow extensively </li></u...
POLYCYTHEMIA <ul><li>Relative  (e.g., hemoconcentration) </li></ul><ul><li>Absolute </li></ul><ul><ul><li>POLYCYTHEMIA  VE...
P. VERA <ul><li>A “myeloproliferative” disease </li></ul><ul><li>ALL cell lines are increased, not just RBCs </li></ul>www...
BLEEDING DISORDERS (aka, Hemorrhagic “DIATHESES”) <ul><li>Blood vessel wall abnormalities √ </li></ul><ul><li>Reduced plat...
VESSEL WALL ABNORMALITIES (NON-thrombotic cytopenic purpuras ) <ul><li>Infections, especially, meningococcemia, and ricket...
THROMBOCYTOPENIAS <ul><li>Like RBCs: </li></ul><ul><ul><li>DE-creased production </li></ul></ul><ul><ul><li>IN-creased des...
DE-CREASED PRODUCTION <ul><li>APLASTIC ANEMIA </li></ul><ul><li>ACUTE LEUKEMIAS </li></ul><ul><li>ALCOHOL, THIAZIDES, CHEM...
IN-CREASED DESTRUCTION <ul><li>AUTOIMMUNE (ITP) </li></ul><ul><li>POST-TRANSFUSION (NEONATAL) </li></ul><ul><li>QUINIDINE,...
THROMBOCYTOPENIAS <ul><li>ITP (Idiopathic Thrombocytopenic Purpura) </li></ul><ul><li>Acute Immune </li></ul><ul><li>DRUG-...
I.T.P. <ul><li>ADULTS AND ELDERLY </li></ul><ul><li>ACUTE OR CHRONIC </li></ul><ul><li>AUTO-IMMUNE </li></ul><ul><li>ANTI-...
ACUTE  ITP <ul><li>CHILDREN </li></ul><ul><li>Follows a VIRAL illness (~ 2 weeks) </li></ul><ul><li>ALSO have anti-platele...
DRUGS <ul><li>Quinine </li></ul><ul><li>Quinidine </li></ul><ul><li>Sulfonamide antibiotics </li></ul><ul><li>HEPARIN </li...
HIV <ul><li>BOTH DE-creased production AND IN-creased destruction factors are present </li></ul>www.freelivedoctor.com
Thrombotic  Microangiopathies <ul><li>BOTH are very SERIOUS CONDITIONS with a HIGH mortality: </li></ul><ul><ul><li>TTP (T...
“ QUALITATIVE” platelet disorders <ul><li>Mostly congenital (genetic): </li></ul><ul><ul><li>Bernard-Soulier syndrome (Gly...
BLEEDING DISORDERS due to CLOTTING FACTOR DEFICIENCIES <ul><li>NOT spontaneous, but following surgery or trauma </li></ul>...
von Willebrand Disease <ul><li>1% prevalence, most common bleeding disorder </li></ul><ul><li>Spontaneous and wound bleedi...
HEMOPHILIA A <ul><li>The “classic” HEMOPHILIA </li></ul><ul><li>Factor VIII decreased </li></ul><ul><li>Co-factor of Facto...
HEMOPHILIA B <ul><li>The “Christmas” HEMOPHILIA </li></ul><ul><li>Factor IX decreased </li></ul><ul><li>Sex-linked recessi...
DIC, Disseminated INTRA-vascular, Coagulation <ul><li>ENDOTHELIAL INJURY </li></ul><ul><li>WIDESPREAD FIBRIN DEPOSITION </...
DIC, Disseminated INTRA-vascular, Coagulation <ul><li>Extremely SERIOUS condition </li></ul><ul><li>NOT a disease in itsel...
Common Coagulation TESTS <ul><li>PTT (intrinsic) </li></ul><ul><li>PT   INR (extrinsic) </li></ul><ul><li>Platelet count,...
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  • RBC 7.4 microns in diameter
  • Topics
  • Classical RBC’s and platelets, as in in the lab or your office with WRIGHT’s stain.
  • Classical features of peripheral white cells
  • Bone marrow biopsy stained with H&amp;E (left), and smear stained with Giemsa (right). BOTH have special advantages!
  • This is a very intense slide, you may have to write a lot of stuff down and listen well!
  • This is also a very INTENSE slide!
  • Platelet analogy.
  • Note lack of a central pallor and a microcytosis, i.e., low MCV
  • G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway .
  • Heinz bodies, precipitated hemoglobin are seen quite well on a methylene blue stain.
  • At first the spleen may be enlarged (left) because of HYPERPLENISM due to hemolysis, later it may infarct itself due to small vessel occlussive disease and be quite small (right), perhaps only 1/10 its normal size.
  • H= High affinity
  • PIGA makes GPI, defective PIGA makes defective or inadequate GPI. Why does the term hemoglobinuria imply hemolysis? What does “paroxysmal” mean” Ans: Sudden, UN-controllable
  • What is the difference between an “agglutinin” and a “hemolysin”? Ans: “-lysis” implies complement fixation
  • The Coombs is a routine test used in the workup of just about ALL kinds of hemolytic anemias
  • Anemias of diminished erythropoesis. Doesn’t this just really boil down to three items?
  • Megaloblasts on top, macrocytes on bottom. What is the difference between a megaloblast and a macrocyte? What is the difference between a megaloblast and an erythroblast?
  • This is the HARD way to remember megaloblastic anemias
  • This is the EASY way
  • A great diagram of the iron cycle. Know what heme, transferrin, ferritin, and hemosiderin are in the iron cycle
  • Relate hypochromia, microcytosis, anisocytosis to the Wintrobe indices: Ans: MCHC, MCV, RDW, respectively
  • Most are hypochromic (low MCHC), and microcytic (low MCV) like Fe deficiency anemias but have NORMAL iron stores (i.e., hemosiderin).
  • Fanconi syndrome and Fanconi anemia are two completely different disorders, but named after the same guy, even though the “syndrome was NOT described by him. Fanconi’s Anemia is characterized by  short stature , skeletal anomalies, increased incidence of solid tumors and leukemias, bone marrow failure ( aplastic anemia ), and cellular sensitivity to DNA damaging agents such as  mitomycin C . If you understand the cell differentiation concept, why would an aplastic anemia be less likely to involve lymphocytes?
  • The NORMAL adult RED bone marrow in the axial skeleton should be about 50% cells and 50% fat. What is this? Perhaps around 90:10?
  • Does this sound like the usual suspects again?
  • What do you think the most serious consequence might be for a person with increased RBCs and platelets?
  • Doesn’t this really boil down to TWO things? 1) Reduced platelet function, and 2) everything else?
  • Normal platelets, but DAMAGED vessel walls
  • At what platelet count level does SPONTANEOUS bleeding generally occur? Ans: 20K Platelets normally 150K-300K
  • Note the last three items are ALL in the same category
  • At what platelet count level does SPONTANEOUS bleeding generally occur? Ans: 20K Platelets normally 150K-300K
  • Any thrombocytopenia of increased destruction should have INCREASED megakaryocytes in the marrow! JUST LIKE a hemolytic anemia has an erythroid HYPER-plasia, same principle!
  • For all practical purposes, the same as Hemophilia A. How to differentiate? Factor assays! Note the AMAZING similarities between Hemophilia A and B
  • What is a “consumptive” coagulopathy? Ans: the platelets and many clotting factors are “consumed”, i.e., used up!
  • Rbc

    1. 1. RBC and BLEEDING DISORDERS www.freelivedoctor.com
    2. 2. RBC and Bleeding Disorders <ul><li>NORMAL </li></ul><ul><ul><li>Anatomy, histology </li></ul></ul><ul><ul><li>Development </li></ul></ul><ul><ul><li>Physiology </li></ul></ul><ul><li>ANEMIAS </li></ul><ul><ul><li>Blood loss: acute, chronic </li></ul></ul><ul><ul><li>Hemolytic </li></ul></ul><ul><ul><li>Diminished erythropoesis </li></ul></ul><ul><li>POLYCYTHEMIA </li></ul><ul><li>BLEEDING DISORDERS </li></ul>www.freelivedoctor.com
    3. 3. www.freelivedoctor.com Classical RBC’s and platelets,
    4. 4. www.freelivedoctor.com Classical features of peripheral white cells
    5. 5. www.freelivedoctor.com Adult Reference Ranges for Red Blood Cells Measurement (units) Men Women Hemoglobin (gm/dL) 13.6–17.2 12.0–15.0 Hematocrit (%) 39–49 33–43 Red cell count (10 6 /µL) 4.3–5.9 3.5–5.0 Reticulocyte count (%) 0.5–1.5 Mean cell volume (µm 3 ) 82–96 Mean corpuscular hemoglobin (pg) 27–33 Mean corpuscular hemoglobin concentration (gm/dL) 33–37 RBC distribution width 11.5–14.5
    6. 6. www.freelivedoctor.com Bone marrow biopsy stained with H&E (left), and smear stained with Giemsa (right).
    7. 7. WHERE is MARROW? <ul><li>Yolk Sac: very early embryo </li></ul><ul><li>Liver, Spleen: NEWBORN </li></ul><ul><li>BONE </li></ul><ul><ul><li>CHILDHOOD: AXIAL SKELETON & APPENDICULAR SKELETON BOTH HAVE RED (active) MARROW </li></ul></ul><ul><ul><li>ADULT: AXIAL SKELETON RED MARROW, APPENDICULAR SKELETON YELLOW MARROW </li></ul></ul>www.freelivedoctor.com
    8. 8. MARROW FEATURES <ul><li>CELLULARITY </li></ul><ul><li>MEGAKARYOCYTES </li></ul><ul><li>M:E RATIO </li></ul><ul><li>MYELOID MATURATION </li></ul><ul><li>ERYTHROID MATURATION </li></ul><ul><li>LYMPHS, PLASMA CELLS </li></ul><ul><li>STORAGE IRON, i.e., HEMOSIDERIN </li></ul><ul><li>“ FOREIGN CELLS” </li></ul>www.freelivedoctor.com
    9. 9. MARROW “ DIFFERENTIATION” www.freelivedoctor.com
    10. 10. www.freelivedoctor.com
    11. 11. ANEMIAS* <ul><li>BLOOD LOSS </li></ul><ul><ul><li>ACUTE </li></ul></ul><ul><ul><li>CHRONIC </li></ul></ul><ul><li>IN-creased destruction (HEMOLYTIC) </li></ul><ul><li>DE-creased production </li></ul>* A good definition would be a decrease in OXYGEN CARRYING CAPACITY, rather than just a decrease in red blood cells, because you need to have enough blood cells THAT FUNCTION, and not just enough blood cells. www.freelivedoctor.com
    12. 12. Features of ALL anemias <ul><li>Pallor, where? </li></ul><ul><li>Tiredness </li></ul><ul><li>Weakness </li></ul><ul><li>Dyspnea, why? </li></ul><ul><li>Palpitations </li></ul><ul><li>Heart Failure (high output), why? </li></ul>www.freelivedoctor.com
    13. 13. www.freelivedoctor.com Blood Loss Acute: trauma Chronic: lesions of gastrointestinal tract, gynecologic disturbances. The features of chronic blood loss anemia are the same as iron deficiency anemia, and is defined as a situation in which the production cannot keep up with the loss
    14. 14. HEMOLYTIC <ul><li>HEREDITARY </li></ul><ul><ul><li>MEMBRANE disorders: e.g., spherocytosis </li></ul></ul><ul><ul><li>ENZYME disorders: e.g., G6PD deficciency </li></ul></ul><ul><ul><li>HGB disorders (hemoglobinopathies) </li></ul></ul><ul><li>ACQUIRED </li></ul><ul><ul><li>MEMBRANE disorders (PNH) </li></ul></ul><ul><ul><li>ANTIBODY MEDIATED, transfusion or autoantibodies </li></ul></ul><ul><ul><li>MECHANICAL TRAUMA </li></ul></ul><ul><ul><li>INFECTIONS </li></ul></ul><ul><ul><li>DRUGS, TOXINS </li></ul></ul><ul><ul><li>HYPERSPLENISM </li></ul></ul>www.freelivedoctor.com
    15. 15. IMPAIRED PRODUCTION <ul><li>Disturbance of proliferation and differentiation of stem cells: aplastic anemias, pure RBC aplasia, renal failure </li></ul><ul><li>Disturbance of proliferation and maturation of erythroblasts </li></ul><ul><li>Defective DNA synthesis: (Megaloblastic) </li></ul><ul><li>Defective heme synthesis: (Fe) </li></ul><ul><li>Deficient globin synthesis: (Thalassemias) </li></ul>www.freelivedoctor.com
    16. 16. MODIFIERS <ul><li>MCV, microcytosis, macrocytosis </li></ul><ul><li>MCH </li></ul><ul><li>MCHC, hypochromic </li></ul><ul><li>RDW, anisocytosis </li></ul>www.freelivedoctor.com
    17. 17. HEMOLYTIC ANEMIAS <ul><li>Life span LESS than 120 days </li></ul><ul><li>Marrow hyperplasia (M:E), EPO+ </li></ul><ul><li>Increased catabolic products, e.g., bilirubin, serum HGB, hemosiderin </li></ul>www.freelivedoctor.com
    18. 18. HEMOLYSIS <ul><li>INTRA-vascular (vessels) </li></ul><ul><li>EXTRA-vascular (spleen) </li></ul>www.freelivedoctor.com
    19. 19. HEREDITARY SPHEROCYTOSIS Genetic defects affecting ankyrin, spectrin, usually autosomal dominant Children, adults Anemia, hemolysis, jaundice, splenomegaly, gallstones (what kind?) www.freelivedoctor.com
    20. 20. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency <ul><li>A - and Mediterranean are most significant types </li></ul>www.freelivedoctor.com
    21. 21. FEATURES of G6PD Defic. <ul><li>Genetic: Recessive, X-linked </li></ul><ul><li>Can be triggered by foods (fava beans), oxidant substances drugs (primaquine, chloroquine), or infections </li></ul><ul><li>HGB can precipitate as HEINZ bodies </li></ul><ul><li>Acute intravascular hemolysis can occur: </li></ul><ul><ul><li>Hemoglobinuria </li></ul></ul><ul><ul><li>Hemoglobinemia </li></ul></ul><ul><ul><li>Anemia </li></ul></ul>www.freelivedoctor.com
    22. 22. Sickle Cell Disease <ul><li>Classic hemoglobinopathy </li></ul><ul><li>Normal HGB is α 2 β 2: β -chain defects (Val->Glu) </li></ul><ul><li>Reduced hemoglobin “sickles” in homozygous </li></ul><ul><li>8% of American blacks are heterozygous </li></ul>www.freelivedoctor.com
    23. 23. Clinical features of HGB-S disease <ul><li>Severe anemia </li></ul><ul><li>Jaundice </li></ul><ul><li>PAIN (pain CRISIS) </li></ul><ul><li>Vaso-occlusive disease: EVEREWHERE, but clinically significant bone, spleen (autosplenectomy) </li></ul><ul><li>Infections: Pneumococcus, Hem. Influ . </li></ul>www.freelivedoctor.com
    24. 24. www.freelivedoctor.com
    25. 25. THALASSEMIAS <ul><li>A WIDE VARIETY of diseases involving GLOBIN synthesis, COMPLEX genetics </li></ul><ul><li>Alpha or beta chains deficient synthesis involved </li></ul><ul><li>Often termed MAJOR or MINOR, depending on severity, silent carriers and “traits” are seen </li></ul><ul><li>HEMOLYSIS is uniformly a feature, a microcytic anemia </li></ul><ul><li>A “crew cut” skull x-ray appearance may be seen </li></ul>www.freelivedoctor.com
    26. 26. Hemoglobin H Disease <ul><li>Deletion of THREE alpha chain genes </li></ul><ul><li>HGB-H is primarilly Asian </li></ul><ul><li>HGB-H has a HIGH affinity for oxygen </li></ul><ul><li>HGB-H is unstable and therefore has classical hemolytic behavior </li></ul>www.freelivedoctor.com
    27. 27. HYDROPS FETALIS <ul><li>FOUR alpha chain genes are deleted, so this is the MOST SEVERE form of thalassemia </li></ul><ul><li>Many/most never make it to term </li></ul><ul><li>Children born will have a SEVERE hemolytic anemia as in the erythroblastosis fetalis of Rh disease: </li></ul><ul><ul><li>Pallor (as in all anemias) </li></ul></ul><ul><ul><li>Edema (hence the name “hydrops”) </li></ul></ul><ul><ul><li>Massive hepatosplenomegaly (hemolysis) </li></ul></ul>www.freelivedoctor.com
    28. 28. Paroxysmal Nocturnal Hemoglobinuria (PNH) <ul><li>ACQUIRED, NOT INHERITED like all the previous hemolytic anemias were </li></ul><ul><li>ACQUIRED mutations in phosphatidylinositol glycan A (PIGA) </li></ul><ul><li>It is “P” and “N” only 25% of the time </li></ul>G lycosylphos P hatidyl I nositol www.freelivedoctor.com
    29. 29. Immunohemolytic Anemia <ul><li>All of these have the presence of antibodies and/or compliment present on RBC surfaces </li></ul><ul><li>NOT all are AUTOimmune, some are caused by drugs </li></ul><ul><li>Antibodies can be </li></ul><ul><ul><li>WARM (IgG) </li></ul></ul><ul><ul><li>COLD AGGLUTININ (IgM) </li></ul></ul><ul><ul><li>COLD HEMOLYSIN (paroxysmal) (IgG) </li></ul></ul>www.freelivedoctor.com
    30. 30. IMMUNOHEMOLYTIC ANEMIAS <ul><li>WARM (IgG), will NOT hemolyze at room temp </li></ul><ul><ul><li>Primary Idiopathic (most common) </li></ul></ul><ul><ul><li>Secondary (Tumors, especially leuk/lymph, drugs) </li></ul></ul><ul><li>COLD AGGLUTININS: (IgM), WILL hemolyze at room temp </li></ul><ul><ul><li>Mycoplasma pneumoniae, HIV, mononucleosis </li></ul></ul><ul><li>COLD HEMOLYSINS: (IgG) Cold Paroxysmal Hemoglobinuria, hemo-LYSIS in body, ALSO often follows mycoplasma pneumoniae </li></ul>www.freelivedoctor.com
    31. 31. COOMBS TEST <ul><li>DIRECT: Patient’s CELLS are tested for surface Ab’s </li></ul><ul><li>INDIRECT: Patient’s SERUM is tested for Ab’s. </li></ul>www.freelivedoctor.com
    32. 32. HEMOLYSIS/HEMOLYTIC ANEMIAS DUE TO RBC TRAUMA <ul><li>Mechanical heart valves breaking RBC’s </li></ul><ul><li>MICROANGIOPATHIES: </li></ul><ul><ul><li>TTP </li></ul></ul><ul><ul><li>Hemolytic Uremic Syndrome </li></ul></ul>www.freelivedoctor.com
    33. 33. NON-Hemolytic Anemias: i.e., DE-creased Production <ul><li>“ Megaloblastic” Anemias </li></ul><ul><li>B12 Deficiency (Pernicious Anemia) </li></ul><ul><li>Folate Deficiency </li></ul><ul><li>Iron Deficiency </li></ul><ul><li>Anemia of Chronic Disease </li></ul><ul><li>Aplastic Anemia </li></ul><ul><li>“ Pure” Red Cell Aplasia </li></ul><ul><li>OTHER forms of Marrow Failure </li></ul>www.freelivedoctor.com
    34. 34. MEGALOBLASTIC ANEMIAS <ul><li>Differentiating megaloblasts (marrow) from macrocytes (peripheral smear, MCV>94) </li></ul><ul><li>Impaired DNA synthesis </li></ul><ul><li>For all practical purposes, also called the anemias of B12 and FOLATE deficiency </li></ul>www.freelivedoctor.com
    35. 35. www.freelivedoctor.com Decreased intake Inadequate diet, vegetarianism Impaired absorption Intrinsic factor deficiency    Pernicious anemia      Gastrectomy      Malabsorption states    Diffuse intestinal disease, e.g., lymphoma, systemic sclerosis Ileal resection, ileitis    Competitive parasitic uptake    Fish tapeworm infestation      Bacterial overgrowth in blind loops and diverticula of bowel Increased requirement Pregnancy, hyperthyroidism, disseminated cancer
    36. 36. Vit-B12 Physiology <ul><li>Oral ingestion </li></ul><ul><li>Combines with INTRINSIC FACTOR in the gastric mucosa </li></ul><ul><li>Absorbed in the terminal ileum </li></ul><ul><li>DEFECTS at ANY of these sites can produce a MEGALOBLASTIC anemia </li></ul>www.freelivedoctor.com
    37. 37. Please remember that ALL megaloblastic anemias are also MACROCYTIC (MCV>94 or MCV~100), and that not only are the RBC’s BIG, but so are the neutrophils, and neutrophilic precursors in the bone marrow too, and even more so, HYPERSEGMENTED!!! www.freelivedoctor.com
    38. 38. PERNICIOUS ANEMIA <ul><li>MEGALOBLASTIC anemia </li></ul><ul><li>LEUKOPENIA and HYPERSEGS </li></ul><ul><li>JAUNDICE </li></ul><ul><li>NEUROLOGIC posterolateral spinal tracts </li></ul><ul><li>ACHLORHYDRIA </li></ul><ul><li>Can’t absorb B12 </li></ul><ul><li>LOW serum B12 </li></ul><ul><li>Flunk Schilling test, i.e., can’t absorb B12, using a radioactive tracer </li></ul>www.freelivedoctor.com
    39. 39. FOLATE DEFICIENCY MEGALOBLASTIC AMEMIAS <ul><li>Decreased Intake: diet, etoh-ism, infancy </li></ul><ul><li>Impaired Absorption: intestinal disease </li></ul><ul><li>DRUGS: anticonvulsants, BCPs, CHEMO </li></ul><ul><li>Increased Loss: Hemodialysis </li></ul><ul><li>Increased Requirement: Pregnancy, infancy </li></ul><ul><li>Impaired Usage  </li></ul>www.freelivedoctor.com
    40. 40. Fe Deficiency Anemia <ul><li>Due to increased loss or decreased ingestion, almost always, in USA, nowadays, increased loss is the reason </li></ul><ul><li>Macrocytic (low MCV), Hypochromic (low MCHC) </li></ul><ul><li>THE ONLY WAY WE CAN LOSE IRON IS BY LOSING BLOOD </li></ul>www.freelivedoctor.com
    41. 41. Fe Transferrin Ferritin (GREAT test) Hemosiderin www.freelivedoctor.com
    42. 42. Clinical Fe-Defic-Anemia <ul><li>Adult men: GI Blood Loss </li></ul><ul><li>PRE menopausal women: menorrhagia </li></ul><ul><li>POST menopausal women: GI Blood Loss </li></ul>www.freelivedoctor.com
    43. 43. www.freelivedoctor.com
    44. 44. 2 BEST lab tests: <ul><li>Serum Ferritin </li></ul><ul><li>Prussian blue hemosiderin stain of marrow (also called an “iron” stain) </li></ul>www.freelivedoctor.com
    45. 45. Anemia of Chronic Disease <ul><li>CHRONIC INFECTIONS </li></ul><ul><li>CHRONIC IMMUNE DISORDERS </li></ul><ul><li>NEOPLASMS </li></ul><ul><li>LIVER, KIDNEY failure </li></ul>www.freelivedoctor.com
    46. 46. APLASTIC ANEMIAS <ul><li>ALMOST ALWAYS involve platelet and WBC suppression as well </li></ul><ul><li>Some are idiopathic, but MOST are related to drugs, radiation </li></ul><ul><li>FANCONI’s ANEMIA is the only one that is inherited, and NOT acquired </li></ul><ul><li>Act at STEM CELL level, except for “pure” red cell aplasia </li></ul>www.freelivedoctor.com
    47. 47. APLASTIC ANEMIAS www.freelivedoctor.com
    48. 48. APLASTIC ANEMIAS <ul><li>CHLORAMPHENICOL </li></ul><ul><li>OTHER ANTIBIOTICS </li></ul><ul><li>CHEMO </li></ul><ul><li>INSECTICIDES </li></ul><ul><li>VIRUSES </li></ul><ul><ul><li>EBV </li></ul></ul><ul><ul><li>HEPATITIS </li></ul></ul><ul><ul><li>VZ </li></ul></ul>www.freelivedoctor.com
    49. 49. MYELOPHTHISIC ANEMIAS <ul><li>Are anemias caused by metastatic tumor cells replacing the bone marrow extensively </li></ul>www.freelivedoctor.com
    50. 50. POLYCYTHEMIA <ul><li>Relative (e.g., hemoconcentration) </li></ul><ul><li>Absolute </li></ul><ul><ul><li>POLYCYTHEMIA VERA (Primary) ( LOW EPO) </li></ul></ul><ul><ul><li>POLYCYTHEMIA (Secondary) (HIGH EPO) </li></ul></ul><ul><ul><ul><li>HIGH ALTITUDE </li></ul></ul></ul><ul><ul><ul><li>EPO TUMORS </li></ul></ul></ul><ul><ul><ul><li>EPO “Doping” </li></ul></ul></ul><ul><ul><ul><li>CVAC, the trendy California bubble pods </li></ul></ul></ul>www.freelivedoctor.com
    51. 51. P. VERA <ul><li>A “myeloproliferative” disease </li></ul><ul><li>ALL cell lines are increased, not just RBCs </li></ul>www.freelivedoctor.com
    52. 52. BLEEDING DISORDERS (aka, Hemorrhagic “DIATHESES”) <ul><li>Blood vessel wall abnormalities √ </li></ul><ul><li>Reduced platelets √ </li></ul><ul><li>Decreased platelet function √ </li></ul><ul><li>Abnormal clotting factors √ </li></ul><ul><li>DIC (Disseminated INTRA-vascular Coagulation) </li></ul>www.freelivedoctor.com
    53. 53. VESSEL WALL ABNORMALITIES (NON-thrombotic cytopenic purpuras ) <ul><li>Infections, especially, meningococcemia, and rickettsia </li></ul><ul><li>Drug reactions causing a leukocytoclastic vasculitis </li></ul><ul><li>Scurvy, Ehlers-Danlos, Cushing syndrome </li></ul><ul><li>Henoch-Schönlein purpura (mesangial deposits too) </li></ul><ul><li>Hereditary hemorrhagic telangiectasia </li></ul><ul><li>Amyloid </li></ul>www.freelivedoctor.com
    54. 54. THROMBOCYTOPENIAS <ul><li>Like RBCs: </li></ul><ul><ul><li>DE-creased production </li></ul></ul><ul><ul><li>IN-creased destruction </li></ul></ul><ul><ul><li>Sequestration (Hypersplenism) </li></ul></ul><ul><ul><li>Dilutional </li></ul></ul><ul><li>Normal value 150K-300K </li></ul>www.freelivedoctor.com
    55. 55. DE-CREASED PRODUCTION <ul><li>APLASTIC ANEMIA </li></ul><ul><li>ACUTE LEUKEMIAS </li></ul><ul><li>ALCOHOL, THIAZIDES, CHEMO </li></ul><ul><li>MEASLES, HIV </li></ul><ul><li>MEGALOBLASTIC ANEMIAS </li></ul><ul><li>MYELODYSPLASTIC SYNDROMES </li></ul>www.freelivedoctor.com
    56. 56. IN-CREASED DESTRUCTION <ul><li>AUTOIMMUNE (ITP) </li></ul><ul><li>POST-TRANSFUSION (NEONATAL) </li></ul><ul><li>QUINIDINE, HEPARIN, SULFA </li></ul><ul><li>MONO, HIV </li></ul><ul><li>DIC </li></ul><ul><li>TTP </li></ul><ul><li>“ MICROANGIOPATHIC” </li></ul>www.freelivedoctor.com
    57. 57. THROMBOCYTOPENIAS <ul><li>ITP (Idiopathic Thrombocytopenic Purpura) </li></ul><ul><li>Acute Immune </li></ul><ul><li>DRUG-induced </li></ul><ul><li>HIV associated </li></ul><ul><li>TTP, Hemolytic Uremic Syndrome </li></ul>www.freelivedoctor.com
    58. 58. I.T.P. <ul><li>ADULTS AND ELDERLY </li></ul><ul><li>ACUTE OR CHRONIC </li></ul><ul><li>AUTO-IMMUNE </li></ul><ul><li>ANTI-PLATELET ANTIBODIES PRESENT </li></ul><ul><li>INCREASED MARROW MEGAKARYOCYTES </li></ul><ul><li>Rx: STEROIDS </li></ul>www.freelivedoctor.com
    59. 59. ACUTE ITP <ul><li>CHILDREN </li></ul><ul><li>Follows a VIRAL illness (~ 2 weeks) </li></ul><ul><li>ALSO have anti-platelet antibodies </li></ul><ul><li>Platelets usually return to normal in a few months </li></ul>www.freelivedoctor.com
    60. 60. DRUGS <ul><li>Quinine </li></ul><ul><li>Quinidine </li></ul><ul><li>Sulfonamide antibiotics </li></ul><ul><li>HEPARIN </li></ul>www.freelivedoctor.com
    61. 61. HIV <ul><li>BOTH DE-creased production AND IN-creased destruction factors are present </li></ul>www.freelivedoctor.com
    62. 62. Thrombotic Microangiopathies <ul><li>BOTH are very SERIOUS CONDITIONS with a HIGH mortality: </li></ul><ul><ul><li>TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA) </li></ul></ul><ul><ul><li>H.U.S. (HEMOLYTIC UREMIC SYNDROME) </li></ul></ul><ul><li>These can also be called “consumptive” coagulopathies, just like a DIC </li></ul>www.freelivedoctor.com
    63. 63. “ QUALITATIVE” platelet disorders <ul><li>Mostly congenital (genetic): </li></ul><ul><ul><li>Bernard-Soulier syndrome (Glycoprotein-1-b deficiency) </li></ul></ul><ul><ul><li>Glanzmann’s thrombasthenia (Glyc.-IIB/IIIA deficiency) </li></ul></ul><ul><ul><li>Storage pool disorders, i.e., platelets mis-function AFTER they degranulate </li></ul></ul><ul><li>ACQUIRED: ASPIRIN, ASPIRIN, ASPIRIN </li></ul>www.freelivedoctor.com
    64. 64. BLEEDING DISORDERS due to CLOTTING FACTOR DEFICIENCIES <ul><li>NOT spontaneous, but following surgery or trauma </li></ul><ul><li>ALL factor deficiencies are possible </li></ul><ul><li>Factor VIII and IX both are the classic X-linked recessive hemophilias, A and B, respectively </li></ul><ul><li>ACQUIRED disorders often due to Vitamin-K deficiencies </li></ul><ul><li>von Willebrand disease the most common, 1% </li></ul>www.freelivedoctor.com
    65. 65. von Willebrand Disease <ul><li>1% prevalence, most common bleeding disorder </li></ul><ul><li>Spontaneous and wound bleeding </li></ul><ul><li>Usually autosomal dominant </li></ul><ul><li>Gazillions of variants, genetics even more complex </li></ul><ul><li>Prolonged BLEEDING TIME, NL platelet count </li></ul><ul><li>vWF is von Willebrand Factor, which complexes with Factor VIII, it is the von Willebrand Factor which is defective in von Willebrand disease </li></ul><ul><li>Usually BOTH platelet and FactorVIII-vWF disorders are present </li></ul>www.freelivedoctor.com
    66. 66. HEMOPHILIA A <ul><li>The “classic” HEMOPHILIA </li></ul><ul><li>Factor VIII decreased </li></ul><ul><li>Co-factor of Factor IX to activate Factor X </li></ul><ul><li>Sex-linked recessive </li></ul><ul><li>Hemorrhage usually NOT spontaneous </li></ul><ul><li>Wide variety of severities </li></ul><ul><li>Prolonged PTT (intrinsic) only </li></ul><ul><li>Rx: Recombinant Factor VIII </li></ul>www.freelivedoctor.com
    67. 67. HEMOPHILIA B <ul><li>The “Christmas” HEMOPHILIA </li></ul><ul><li>Factor IX decreased </li></ul><ul><li>Sex-linked recessive </li></ul><ul><li>Hemorrhage usually NOT spontaneous </li></ul><ul><li>Wide variety of severities </li></ul><ul><li>Prolonged PTT (intrinsic) only </li></ul><ul><li>Rx: Recombinant Factor IX </li></ul>www.freelivedoctor.com
    68. 68. DIC, Disseminated INTRA-vascular, Coagulation <ul><li>ENDOTHELIAL INJURY </li></ul><ul><li>WIDESPREAD FIBRIN DEPOSITION </li></ul><ul><li>HIGH MORTALITY </li></ul><ul><li>ALL MAJOR ORGANS COMMONLY INVOLVED </li></ul>www.freelivedoctor.com
    69. 69. DIC, Disseminated INTRA-vascular, Coagulation <ul><li>Extremely SERIOUS condition </li></ul><ul><li>NOT a disease in itself but secondary to many conditions </li></ul><ul><ul><li>Obstetric: MAJOR OB complications, toxemia, sepsis, abruption </li></ul></ul><ul><ul><li>Infections: Gm-, meningococcemia, RMSF, fungi, Malaria </li></ul></ul><ul><ul><li>Many neoplasms, acute promyelocytic leukemia </li></ul></ul><ul><ul><li>Massive tissue injury: trauma, burns, surgery </li></ul></ul><ul><li>“ Consumptive” coagulopathy </li></ul>www.freelivedoctor.com
    70. 70. Common Coagulation TESTS <ul><li>PTT (intrinsic) </li></ul><ul><li>PT  INR (extrinsic) </li></ul><ul><li>Platelet count, aggregation </li></ul><ul><li>Bleeding Time, so EASY to do </li></ul><ul><li>Fibrinogen </li></ul><ul><li>Factor Assays </li></ul>www.freelivedoctor.com
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