1. MLAB 1415: Hematology Keri Brophy-Martinez Chapter 18: Hemolytic Anemia: Nonimmune Defects

2. Nonimmune Hemolytic Anemia These anemias represent a group of conditions that lead to the shortened survival of red cells by various mechanisms. Causes  Antagonists Hemolysis precipitated by either injury to the RBC membrane or to denaturation of hgb Toxins, infectious agents  Physical trauma Hemolysis caused by physical injury to RBC

3. Antagonists: Infectious Agents Parasites: Intracellular infections Malaria  Carried by mosquito  Release of the parasite from the cell causes cell lysis  Species of malaria include:  Plasmodium vivax  P. faciparum - most fatal  P. malariae - uncommon  P. ovale - uncommon  Peripheral smear examination will reveal intracellular parasites Babesiosis  Tick-borne  Peripheral smear examination will reveal intracellular parasites

4. Antagonists: Infectious Agents Extracellular infections  Bartonellosis Transmitted by sand fly or direct inoculation by scratch or bite of a mammal Restricted to South America Induces pitting or invagination or RBC membrane  Clostridium perfringens Exotoxin production affects integrity of host cell membrane

5. Antagonists Venoms  Some spiders contain enzymes that lyse the red cell membrane (i.e Brown Recluse). Snake venoms rarely cause lysis directly. Burns  Burns over more than 15% of the body can cause hemolysis.  Anemia occurs within 24-46 hours post-burn  It is thought that the direct effect of the heat on spectrin, causes the red cells to fragment and burst.

6. Physical Injury or Trauma Intravascular and/or extravascular hemolysis Striking abnormal shapes of the circulating blood, such as fragments and helmut cells

7. Physical Injury or Trauma Categories  Microangiopathic hemolytic anemia HUS, TTP,DIC, Malignant hypertension  Other physical trauma Burns, cardiac prothesis, exercise-induced hemoglobinuria

8. Microangiopathic hemolytic anemia (MAHA) Fragmentation of the red cells by fibrin strands as they pass through abnormal arterioles. The fibrin strands are the results of intravascular coagulation

9. Underlying Conditions of MAHA Hemolytic uremic syndrome= HUS Thrombotic Thrombocytopenic Purpura= TTP Malignant Hypertension Disseminated Cancer Pregnancy

10. HUS: Hemolytic Uremic Syndrome  Multisystem Disorder  Onset between 6 months- 5 years  Triad of clinical findings Hemolytic anemia with RBC fragments Thrombocytopenia Acute nephropathy  Classifed based on presence or absence of diarrhea

11. Pathophysiology 70% of cases associated with Shiga toxin produced by E. coli 0157:H7 Organism enters human GI tract, damages the mucosa and the toxin in absorbed Toxin activates the platelets Platelet thrombi trap RBCs and fragment then

12. Clinical Findings Onset acute Sudden pallor Abdominal pain Vomiting Foul-smelling and bloody diarrhea Jaundice Hematuria Possible acute renal failure

13. TTP: Thrombotic Thrombocytopenic Purpura  Platelets and VWF aggregate on the microvascular endothelium. As RBC are forced through the aggregates, fragmentation occurs  Affects young adults, especially females  Infections and pregnancy are common precipitating factors

14. Lab Features in HUS and TTP Evidence of HemolysisDecreased H and H Increased reticulocytes/polychromasia Thrombocytopenia Leukocytosis with left shift Schistocytes Evidence of Intravascular HemolysisHemoglobinemia Hemoglobinuria Decreased haptoglobin Increased total & unconjugated bilirubin Evidence of Thrombotic Microangiopathy Thrombocytopenia

15. DIC: Disseminated Intravascular Coagulation  Bacterial sepsis, neoplasms, immunologic disorders or trauma can precipitate DIC  As coagulation is activated, fibrin is deposited in the microvasculature  RBC become trapped in the fibrin meshwork and then fragment

16. Physical Injury or Trauma Malignant Hypertension  Peripheral smear shows RBC fragments, low platelet count, mechanism unknown Cardiac prothesis (heart valves)  Peripheral smear shows RBC fragments, helmet cells and occasional spherocytes. March hemoglobinurea/ Exercise-Induced  Caused by traumatic destruction of the red cells in strenuous and sustained physical activity such as marching or running