1 / 28

Life of a Red Blood Cell

Life of a Red Blood Cell. Erythroid precursors undergo 4-5 divisions in marrow, extrude nucleus, become reticulocytes, enter peripheral blood, and survive ~100-120 days

ghazi
Download Presentation

Life of a Red Blood Cell

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Life of a Red Blood Cell • Erythroid precursors undergo 4-5 divisions in marrow, extrude nucleus, become reticulocytes, enter peripheral blood, and survive ~100-120 days • Must withstand severe mechanical & metabolic stress, deform to pass thru capillaries half their size, resist shearing force across heart valves, survive stasis-induced acidemia & substrate depletion, avoid removal by macrophages

  2. Normal Red Blood Cell • Discoid shape with 7-8 micron diameter • Can squeeze thru 3 micron capillary • As it ages, it loses water & surface area, impairing deformability • These changes are detected by the RES and trigger removal of the aged RBCs by macrophages

  3. Anemia • Initial evaluation: MCV • If MCV >100: megaloblastic or not? • If MCV <80: iron deficient or not? • MCV 80-100: reticulocytosis or not? • Increased retics: Hemolysis or posthemorrhage • Decreased retics: Renal dz, liver dz, hypothyroid, anemia of chronic dz, myelodysplasia, leukemia, myeloma, etc.

  4. Hemolytic Anemia • Inadequate number of RBCs caused by premature destruction of RBCs • Severity depends on rate of destruction and the marrow capacity to increase erythroid production (normal marrow can increase production 5 to 8 fold)

  5. Classification of Hemolytic Anemia • Site of RBC destruction-Extravascular or Intravascular • Cause of destruction- extracorpuscular (abnormal elements in vascular bed that “attack” RBCs) or intracorpuscular (erythrocyte defects- membrane abnormalities, metabolic disturbances, disorders of hemoglobin)

  6. Pathways of RBC Destruction • Extravascular: RBCs phagocytized by RE cells; RBC membrane broken down; Hemoglobin broken into CO (lung), bilirubin (conjugation and excretion by liver), and iron (binds to transferrin, returns to marrow) • Intravascular: Free hemoglobin binds to haptoglobin or hemopexin or is converted to methemalbumin. These proteins are cleared by the liver where the heme is broken down to recover iron & produce bilirubin.

  7. Hemolytic Anemias • Intrinsic RBC causes • Membranopathies: hereditary spherocytosis • Enzymopathies: G6PD • Hemoglobinopathies: Sickle cell disease • Extrinsic causes • Immune mediated: Autoimmune (drug, virus, lymphoid malignance) vs Alloimmune (transfusion reaction) • Microangiopathic (TTP) • Infection (Malaria) • Chemical agents (spider venom)

  8. Diagnosis of Hemolysis • Symptoms depend on degree of anemia (ie, rate of destruction) • Clinical features: anemia, jaundice, reticulocytosis, high MCV & RDW, elevated indirect bili, elevated LDH, low haptoglobin, positive DAT (AIHA) • Acute intravascular hemolysis: fever, chills, low back pain, hemoglobinuria • Smear: polychromatophilia, spherocytosis & autoagglutination

  9. Acute Intravascular Hemolysis • Causes: Blood transfusion, thermal burns, snake bites, infections (clostridia, malaria, Bartonella, Mycoplasma), mechanical heart valves, PNH • Hemoglobinemia- pink or red plasma • Hemoglobinuria: brown or red after spinning down RBCs • Urine hemosiderin: urine hemoglobin reabsorbed by renal tubular cells; detect by staining sediment • Low haptoglobin: binds free hemoglobin • Methemalbumin: appears after depletion of haptoglobin

  10. Intravascular hemolysis events • Acute intravascular hemolysis • Immediate drop in Haptoglobin; rises at 2 days; normal at 4 days • Hemoglobinemia detectable 6-12 hrs after event • Hemoglobinuria detectable 12-24 hrs • Hemosiderinuria detectable 3-12 days • Methemalbumin detectable 1-12 days

  11. Acute Extravascular Hemolysis • Sudden fall in hemoglobin level with no evidence of bleeding or intravascular hemolysis (no hemoglobinemia or hemoglobinuria) • Clinical setting usually points to cause

  12. Causes of Extravascular Hemolysis • Bacterial & Viral infections • Drug- induced • Autoimmune • Hemoglobinopathies • Membrane Structural Defects • “Environmental” Disorders- Malignancy associated DIC, TTP, Eclampsia

  13. Infectious causes of hemolysis • 5-20% of pts with falciparum malaria have acute intravascular hemolysis (black water fever); most have mild extravascular hemolysis • Clostridial sepsis may cause severe intravascular hemolysis • Mild hemolysis occurs with mycoplasma pneumonia; often associated with high titer cold agglutinin; self limited

  14. Drug-induced Hemolysis • May occur by an immune mechanism or by challenging the RBC metabolic machinery • Oxidant drugs causing hemolysis in G6PD deficiency: nitrofurantoin, sulfa drugs, dapsone, primaquine, pyridium, doxorubicin • Drugs causing immune-mediated hemolysis: penicillin, quinidine, methyldopa, streptomycin

  15. G6PD Deficiency • ~10% of African-American males have X-linked A variant • The older RBCs are lost from circulation • New RBCs have normal or high G6PD levels; therefore they can usually compensate for the hemolysis even if the drug is continued

  16. Drug Induced Hemolysis • Formation of antibodies specific to the drug: in high doses PCN binds RBC membrane, if pt forms Ab against PCN, the RBC are destroyed • Induction of Ab to RBC membrane antigens:methyldopa induces autoab to Rh ag • Selective binding of streptomycin to RBC membrane with formation of complement fixing antibody • All have Coombs (DAT) positive for IgG

  17. Autoimmune Hemolytic Anemia • Anticipate this cause of hemolysis in infections, collagen vascular diseases, lymphoid malignancies • Generally, acute extravascular hemolysis • Spherocytes seen; no fragments; elevated LDH; suppressed haptoglobin; reticulocytes • Autoantibodies are directed against RBC components (eg, Kell antigen) • May be warm-reacting (IgG) or cold-reacting (IgM) antibody

  18. Autoimmune Hemolytic Anemia • Warm reacting abs will show IgG +/- C3 • Cold reacting abs will have C3 only • RBCs sensitized to IgG only are removed in the spleen; those with complement are destroyed in the liver (Kupffer cells have C3b receptors) • Warm reacting abs often respond to steroids • Cold reacting antibodies are more often resistant to therapy and are associated with lymphoid malignancy

  19. Causes of Autoimmune Hemolysis • SLE • Non-Hodgkins lymphomas, CLL • Hodgkins Disease • Myeloma • HIV • Hepatitis C • Chronic Ulcerative Colitis

  20. Management of Hemolysis • The increase in RBC production requires adequate iron (intravascular hemolysis) & folate supplies (all hemolytic states) • Intravascular hemolysis- transfusion reaction- stop transfusion, IVFs to induce diuresis and mannitol (increases renal blood flow & decreases hemoglobin reabsorption)

  21. Management of Extravascular Hemolysis • Acute self-limited hemolysis in G6PD pts rarely needs Rx; pt education important • Severe hemolysis may require transfusion in addition to therapy aimed at specific trigger • Iron overload becomes a problem in hemoglobinopathies • Parvovirus infection may cause aplastic episodes pts with chronic hemolytic states • Pigment gallstones occur in chronic hemolytic states • Splenectomy reduces RBC destruction in pts with hereditary spherocytosis

  22. Management of Warm-Ab Autoimmune Hemolysis • Steroids block RE clearance of RBCs with IgG or C3 on surface and decrease production of IgG antibody • Prednisone 1 to 1.5 mg/kg/day is usual dose • Most respond within 2 weeks • Very slow taper required • Chemotherapy or splenectomy may help if steroids fail • Transfusions given if needed, may require “least incompatible” blood; likely will be destroyed at the same rate as the patient’s own blood

  23. Management of Cold-Ab Autoimmune Hemolytic Anemia • Usually no treatment required in setting of mycoplasma or EBV infection. • Occasionally transfusion is needed. Washed RBCs have less complement and are less likely to trigger further hemolysis. • Steroids usually do not help • Chemotherapy (eg, cyclophosphamide or chlorambucil) may help • In severe cases, plasmapheresis can reduce intravascular antibody titer • May have dramatic cold sensitivity; warm infusions, avoid cold exposure

More Related