Hemolytic Anemia

Etiology-Hereditary

Familial Atypical Hemolytic-Uremic Syndrome (aHUS) (see Hemolytic-Uremic Syndrome, [[Hemolytic-Uremic Syndrome]])

  • xxx

Hemoglobinopathies

RBC Cell Membrane Defect

  • Cytoskeletal Membrane Defect
  • Lipid Membrane Disorders
  • Membrane Disorders Associated with Abnormalities of Erythrocyte Antigens
    • McLeod Syndrome
    • Rh Deficiency Syndromes
  • Membrane Disorders Associated with Abnormal Transport
    • Hereditary Xerocytosis

RBC Enzyme Defects

  • Glycolytic
    • Aldolase Deficiency
    • Diphosphoglycerate Mutase (DPGM) Deficiency
    • Glucose-6-Phosphate Isomerase (G6PI) Deficiency
    • Glyceraldehyde-3-Phosphate Dehydrogenase (GAPD) Deficiency
    • Hexokinase Deficiency
    • Phosphofructokinase (PFK) Deficiency
    • Phosphoglycerate Kinase (PGK) Deficiency
    • Pyruvate Kinase (PK) Deficiency
    • Triose Phosphate Isomerase (TPI) Deficiency
  • Redox
    • Cytochrome B5 Reductase Deficiency
    • Gamma Glutamylcysteine Synthase Deficiency
    • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]])
    • Glutathione Synthase Deficiency
  • Nucleotide Metabolism
    • Adenylate Kinase Deficiency
    • Pyrimidine 5′-Nucleotidase Deficiency

Porphyrias

  • Congenital Erythropoietic and Hepatoerythropoietic Porphyrias
  • Congenital Erythropoietic Protoporphyria

Etiology-Acquired

Autoimmune Hemolytic Anemia (AIHA)

Warm Autoimmune Hemolytic Anemia (48-70% of AIHA cases)

Cold Autoimmune Hemolytic Anemia

Mixed-Type Autoimmune Hemolytic Anemia

  • Idiopathic
  • Secondary
    • Lymphoproliferative Disorders
    • Autoimmune Disorders

Drug-Induced Autoimmune Hemolytic Anemia

  • General Comments
    • Study of Drugs Most Commonly Associated with Autoimmune Hemolytic Anemia in Berlin Case-Control Surveillance Study (FAKOS) (Br J Haematol, 2011) [MEDLINE]
      • Ceftriaxone (Rocephin) (see Ceftriaxone, [[Ceftriaxone]])
      • Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]]): possible association
      • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac, [[Diclofenac]]): most frequently implicated drug in the study
      • Fludarabine (Fludara) (see Fludarabine, [[Fludarabine]])
      • Oxaliplatin (Eloxatin, Oxaliplatin Medac) (see Oxaliplatin, [[Oxaliplatin]])
      • Piperacillin (see Piperacillin, [[Piperacillin]] and Piperacillin-Tazobactam, [[Piperacillin-Tazobactam]]))
  • Autoimmune Type
    • Cephalosporins (see Cephalosporins, [[Cephalosporins]]: occasional mechanism
      • Cefotetan (Cefotan) (see Cefotetan, [[Cefotetan]])
      • Ceftriaxone (Rocephin) (see Ceftriaxone, [[Ceftriaxone]])
    • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac, [[Diclofenac]]): commonly identified cause of autoimmune hemolytic anemia
    • Levodopa (see Carbidopa-Levodopa, [[Carbidopa-Levodopa]])
    • Mefenamic Acid (Ponstel, Ponstan) (see Mefenamic Acid, [[Mefenamic Acid]])
    • Methyldopa (Aldomet) (see Methyldopa, [[Methyldopa]]): classical mechanism
    • Procainamide (Pronestyl) (see Procainamide, [[Procainamide]])
    • Quinidine (Quinaglute, Quinidex) (see Quinidine, [[Quinidine]])
  • Drug Adsorption Type
  • Neoantigen Type
    • Cephalosporins (see Cephalosporins, [[Cephalosporins]]: usual mechanism
      • Cefotetan (Cefotan) (see Cefotetan, [[Cefotetan]])
      • Ceftriaxone (Rocephin) (see Ceftriaxone, [[Ceftriaxone]])
  • Unknown Mechanism
    • Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]]): possible association
    • Fludarabine (Fludara) (see Fludarabine, [[Fludarabine]])
    • Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]])
    • Oxaliplatin (Eloxatin, Oxaliplatin Medac) (see Oxaliplatin, [[Oxaliplatin]])

Other Antibody-Mediated Hemolytic Anemia

  • Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction, [[Acute Hemolytic Transfusion Reaction]])
  • Cryoglobulinemia (see Cryoglobulinemia, [[Cryoglobulinemia]])
  • Delayed Hemolytic Transfusion Reaction (see Delayed Hemolytic Transfusion Reaction, [[Delayed Hemolytic Transfusion Reaction]])
    • Physiology: anamnestic immune response in patients previously alloimmunized by certain RBC antigens -> extravascular hemolysis (usually)

Chemical Injury to Red Blood Cell

  • General Comments: these agents may cause hemolysis, even in the absence of G6PD deficiency
  • Arsenic (see Arsenic, [[Arsenic]])
  • Arsine Vapor (see Arsine, [[Arsine]])
  • Brown Recluse Spider Bite (Loxoscelism) (see Brown Recluse Spider Bite, [[Brown Recluse Spider Bite]])
  • Copper (see Copper, [[Copper]])
  • Cisplatin (see Cisplatin, [[Cisplatin]])
  • Dapsone (see Dapsone, [[Dapsone]])
  • Hemodialysis with High Tap Water Chloramine Concentration (see Hemodialysis, [[Hemodialysis]])
    • Epidemiology: case reports
    • Physiology: chloramine causes acute oxidative hemolysis
  • Hyperbaric Oxygen/100% Oxygen (see Oxygen, [[Oxygen]])
  • Jequirity Bean (see Jequirity Bean, [[Jequirity Bean]])
  • Lead (see Lead, [[Lead]])
  • Mercury (see Mercury, [[Mercury]])
  • Methylene Blue (see Methylene Blue, [[Methylene Blue]])
  • Nitrates (see Nitrites and Nitrates, [[Nitrites and Nitrates]])
  • Propylene Glycol Intoxication (see Propylene Glycol, [[Propylene Glycol]])
  • Saponin Plant Extracts
  • Scorpion Bite (see Scorpion Bite, [[Scorpion Bite]])
  • Snake Venom
    • Viperidae (Vipers)
    • Cobra
  • Sodium Chlorate (see Sodium Chlorate, [[Sodium Chlorate]]): induces hemolysis and methemoglobinemia
  • Stibine

Hypersplenism (see Splenomegaly, [[Splenomegaly]])

  • Physiology: splenic sequestration of one or more cell lines with destruction -> extravascular hemolysis
  • Clinical

Mechanical Red Blood Cell Destruction

Macroangiopathic Hemolytic Anemia

Microangiopathic Hemolytic Anemia (MAHA) + Thrombocytopenia

Infection

  • Bartonellosis (see Bartonellosis, [[Bartonellosis]])
  • Babesiosis (see Babesiosis, [[Babesiosis]])
  • Clostridium Perfringens (see Clostridium Perfringens, [[Clostridium Perfringens]])
  • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
  • Haemophilus Influenzae-Type B (see Haemophilus Influenzae, [[Haemophilus Influenzae]])
    • Physiology: capsular polysaccharide (polyribosyl ribosyl phosphate) is released during infection and binds to the red blood cell membrane
    • Clinical: hemolysis is both intravascular and extravascular
  • Leishmaniasis (see Leishmaniasis, [[Leishmaniasis]])
  • Malaria (see Malaria, [[Malaria]])
  • Streptococcus Pneumoniae (Pneumococcus) (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]])
  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

Other

  • Near Drowning (see Near Drowning, [[Near Drowning]])
    • Physiology: osmotic toxicity to RBC
  • Severe Hypophosphatemia (see Hypophosphatemia, [[Hypophosphatemia]])
    • Physiology: impaired RBC glycolysis with impaired ATP formation -> spherocyte formation

Paroxysmal Nocturnal Hemoglobinuria (see Paroxysmal Nocturnal Hemoglobinuria, [[Paroxysmal Nocturnal Hemoglobinuria]])

  • Physiology: deficiency of the glycolipid, glycosylphosphatidyl-inositol (GPI), which anchors CD55 and CD59 to membrane -> increased complement-mediated RBC (and granulocyte/platelet) lysis

Physical Injury to Red Blood Cell

  • Heat/Burns (see Burns, [[Burns]])
  • Hypotonic Solutions (IV): results in osmotic RBC lysis
  • Radiation (see Radiation Therapy, [[Radiation Therapy]])

Red Blood Cell Membrane Defects

  • End-Stage Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
    • Physiologic Mechanisms Which Contribute to Hemolysis in Liver Disease
      • Acquired Alterations of Red Blood Cell Membrane
        • Burr Cells (Echinocytes)
        • Spur Cells (Acanthocytes)
        • Stomatocytes: mouth-shaped area of central pallor
        • Target Cells: due to decreased lecithin/cholesterol acyltransferase (LCAT) activity, resulting in increased cholesterol:phospholipid ratio -> absolute increase in surface area of the red blood cell membrane
      • Hypersplenism (see Splenomegaly, [[Splenomegaly]]): due to portal hypertension
  • Acquired Acanthocytosis
  • Acquired Stomatocytosis
  • Spur Cell Hemolysis

Physiology

Background-Iron Physiology

  • Iron: free iron is toxic to cells and is therefore stored in alternate forms
    • Within Cells: iron is complexed to protein, as ferritin or hemosiderin (apoferritin binds to free ferrous iron and stores it in its ferric state)
      • As ferritin accumulates with cells of the reticuloendothelial system, protein aggregates are formed as hemosiderin -> hemosiderin is less readily available for utilization than ferritin is
    • In the Circulation: serum iron is bound to transferrin

Background-Red Blood Cell Physiology

  • Normal Red Blood Cell Lifespan: 110-120 days
    • Definition of Hemolysis: shortening of RBC survival to <100 days
    • Normal Rate of Red Blood Cell Age-Independent Random Hemolysis: rate is <0.05-0.5% per day
  • Hemolysis (Anemia) Results in a Compensatory increase in the Erythropoietin Secretion: increases reticulocyte percentage (and absolute reticulocyte count) -> increases RBC production
    • Reticulocytosis is Found in Most Patients with Hemolytic Anemia (and Acute Hemorrhage)

Predominant Site of Hemolysis

Intravascular Hemolysis (RBC Destruction Within the Vascular Space)

  • General Comments
    • Intravascular Hemolysis Results in Release of Hemoglobin into the Plasma Either as Red Oxyhemoglobin or Brownish Oxidized Methemoglobin: plasma has a red-brown color
      • Free hemoglobin binds to haptoglobin -> hemoglobin-haptoglobin complex is rapidly removed by the liver (results in decreased serum haptoglobin level)
      • Lysed hemoglobin breaks down into alpha-beta dimers, which are small (MW: 34k) and cleared via glomerular filtration by the kidney -> resulting in hemoglobinuria
      • Hemoglobin dimers filtered by the kidney are taken up by renal tubular cells, degraded, and the iron stored as hemosiderin -> when renal tubular cells are later sloughed into the urine (approximately 7 days later), hemosiderinuria can be detected (by the Prussian blue reaction)
  • Autoimmune Hemolytic Anemia (AIHA): may occur in some cases (where IgM forms an antibody-antigen complex on the RBC membrane -> activation of complement with RBC lysis)
    • Cold Agglutinin Syndrome: some cases
  • Favism (see Favism, [[Favism]]): usually intravascular
  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]]): at least partly intravascular
  • Hypotonic Solutions (IV): results in osmotic RBC lysis
  • Infection
  • March Hemoglobinuria: usually intravascular
  • Microangiopathic Hemolytic Anemias (MAHA): usually intravascular
  • Paroxysmal Cold Hemoglobinuria (PCH) (see Paroxysmal Cold Hemoglobinuria, [[Paroxysmal Cold Hemoglobinuria]]): usually intravascular
  • Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria, [[Paroxysmal Nocturnal Hemoglobinuria]]): usually intravascular
  • Rho(D) Immunoglobulin (IV)/b>
  • Sepsis (see Sepsis, [[Sepsis]])
  • Transfusion Reaction
  • Toxins

Extravascular Hemolysis (RBC Destruction in the Spleen, Other Reticuloendothelial Tissues, or Extravasated Blood/Hematoma)

  • General Comments
    • Hepatic Destruction of RBC’s: primary site of destruction of severely damaged RBC’s (especially those coated with complement)
      • Liver receives larger percentage of cardiac output than the spleen
    • Splenic Destruction of RBC’s: primary site of destruction of poorly-deformable RBC’s (spherocytes, etc), due to narrow passage in the cords of Billroth -> macrophage ingestion of RBC’s (with degradation of hemoglobin to iron/biliverdin/carbon monoxide)
      • Biliverdin is converted to unconjugated bilirubin, which is released into the plasma
  • Autoimmune Hemolytic Anemia (AIHA): usually extravascular (most cases are IgG-mediated)
    • Warm Autoimmune Hemolytic Anemia
    • Cold Autoimmune Hemolytic Anemia
    • Drug-Induced Autoimmune Hemolytic Anemia
  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]]): at least partly intravascular
  • Hereditary Elliptocytosis (see Hereditary Elliptocytosis, [[Hereditary Elliptocytosis]])
  • Hereditary Spherocytosis (see Hereditary Spherocytosis, [[Hereditary Spherocytosis]])
  • Hypersplenism (see Splenomegaly, [[Splenomegaly]]): splenic sequestration in sickle cell disease
  • Infection
    • Babesiosis (see Babesiosis, [[Babesiosis]])
    • Bartonellosis (see Bartonellosis, [[Bartonellosis]])
    • Haemophilus Influenzae-Type B (see Haemophilus Influenzae, [[Haemophilus Influenzae]]): hemolysis is both intravascular and extravascular
    • Malaria (see Malaria, [[Malaria]])
  • Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]])
  • Large Granular Lymphocyte Leukemia
  • Oxidants
  • Pyruvate Kinase (PK) Deficiency
  • Sickle Cell Disease (see Sickle Cell Disease, [[Sickle Cell Disease]])
  • Thalassemias (see Thalassemia, [[Thalassemia]]): alpha/beta-types
  • Toxins
    • Copper (see Copper, [[Copper]])
    • Lead (see Lead, [[Lead]])
    • Snake Bites
    • Spider Bites
  • Unstable Hemoglobins

Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

  • MCV and MCH: usually increased in hemolysis (reticulocytes are larger than mature RBC’s)
  • Red Cell Distribution Width (RDW): reflects anisocytosis

Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase, [[Serum Lactate Dehydrogenase]])

  • Etiology of Increased LDH
    • Hemolytic Anemia: may be increased up to 10x normal with intravascular hemoylsis
      • Although LDH is sensitive for hemolysis, it is not specific (can be seen released from neoplastic cells, liver, lung, etc)

Serum Haptoglobin (see Serum Haptoglobin, [[Serum Haptoglobin]])

  • Etiology of Decreased Serum Haptoglobin
    • Hemolytic Anemia: decrease in haptoglobin is more likely in intravascular hemolysis than in extravascular hemolysis
      • However, haptoglobin is an acute phase reactant -> can increase in infections and in other reactive states

Indirect Hyperbilirubinemia (see Hyperbilirubinemia, [[Hyperbilirubinemia]])

  • Etiology of Unconjugated (Indirect) Bilirubinemia
    • Hemolytic Anemia: but this is not specific, as it can also occur in Gilbert’s disease
      • In hemolysis, indirect bilirubin is usually <3 mg/dL (higher levels of indirect bilirubinemia indicate the presence of liver disease)

Urine Bilirubin (see Urine Bilirubin, [[Urine Bilirubin]])

  • Physiology: the kidneys do not filter unconjugated bilirubin (as it is avidly bound to albumin) -> therefore, the presence of bilirubinuria indicates the presence of conjugated bilirubinemia
  • Etiology of Bilirubinuria
    • xxx

Urine Hemoglobin (Hemoglobinuria) + Urine Hemosiderin (Hemosiderinuria) (see Hemoglobinuria, [[Hemoglobinuria]] and Hemosiderinuria, [[Hemosiderinuria]])

  • Physiology: with intravascular hemolysis, hemoglobin is released from hemolyzed RBC’s into the blood, exceeding the binding capacity of haptoglobin -> excess hemoglobin is filtered by the kidney
    • Some of this hemoglobin is excreted in the urine, resulting in hemoglobinuria (with “coca cola-colored” urine)
    • Some of this hemoglobin is reabsorbed in the proximal convoluted tubule, where the iron portion is removed and stored in ferritin or hemosiderin -> proximal tubule cells slough off (containing the hemosiderin) and are excreted into the urine, resulting in hemosiderinuria
      • Urine hemosiderin (composed of a complex of ferritin, denatured ferritin, and other material) can be detected in iron-stained urinary sediment (within the sloughed proximal tubular cells)
  • Diagnostic Utility
    • Urine hemoglobin disappears more quickly from the urine than hemosiderin, making it less sensitive for the presence of hemolysis (especially in cases with intermittent hemolysis)
    • Urine Hemosiderin can remain in the urine for several weeks (making it a more sensitive marker for hemolysis in the recent past): however, after an acute episode of intravascular hemolysis, several days may pass before urinary hemosiderin can be detected

Urobilinogen

  • Etiology of Increased Urobilinogen: in urine and stool
    • Hemolytic Anemia

Reticulocyte Count (see Reticulocyte Count, [[Reticulocyte Count]])

  • Reticulocytes are newly-released RBC’s: they are slightly larger than mature RBC’s and have some residual ribosomal RNA -> presence of RNA allows for staining, with detection and counting
  • Normal Reticulocyte Percentage: 1-2%
  • Reticulocyte Production Index (RPI) = Reticulocyte Percentage x (Patient’s Hct/Normal Hct): corrects reticulocyte percentage for the degree of anemia (normalized to Hct 45%)
    • Use Normal Hct = 45%
    • Reticulocyte Production Index > or = to 2.5%: indicates adequate bone marrow response to anemia [MEDLINE]
      • Acute/Subacute Hemorrhage: note that acute hemorrhage may not result in an increased RPI, due to the time that it takes to increase epo synthesis and increase bone marrow RBC production
      • Hemolytic Anemia
    • Reticulocyte Production Index <2.5%: indicates inadequate bone marrow response to anemia [MEDLINE]
      • Chronic Anemia
      • Hypoproliferative Anemia: such as iron deficiency, marrow hyporesponsiveness, aplasia, etc
      • Maturation Disorder: such as vitamin B2 deficiency, etc

Direct Coombs Test (Direct Anti-Globulin Test) (see Direct Coombs Test, [[Direct Coombs Test]])

  • Usually Positive in Immune Hemolytic Anemias: however, about 5-10% of autoimmune hemolytic anemia cases are direct Coombs-negative
    • Polybrene Test: can be used to diagnose direct Coombs-negative autoimmune hemolytic anemia

Iron Studies

  • Iron (see Serum Iron, [[Serum Iron]]): serum iron level represents the amount of circulating iron that is bound to transferrin (although this level varies diurnally)
    • Normal: 50-150 ug/dL
  • Total Iron Binding Capacity (TIBC): indirect measure of the amount of circulating transferrin
    • Normal: 300-360 ug/dL
  • Transferrin Saturation (Iron/TIBC ratio x 100)
    • Normal: 15-45%
    • Level <15%: indicates iron deficiency
    • Level 45-100%: indicates iron overload
  • Serum Ferritin (see Serum Ferritin, [[Serum Ferritin]]): represents the total body iron store
    • Normal (female): 20-200 ug/L -> average 100 ug/L
    • Normal (male): 20-300 ug/L -> average 30 ug/L
    • Level <12: indicates iron deficiency
    • Level 300-4000: indicates iron overload
  • Iron Studies in Various Disease States

ironstudies

Serum Vitamin B12 Level (see Serum Vitamin B12 Level, [[Serum Vitamin B12 Level]])

  • Decreased in Vitamin B12 Deficiency

Serum Folate Level (see Serum Folate Level, [[Serum Folate Level]])

  • Decreased in Folate Deficiency

Peripheral Blood Smear (see Peripheral Blood Smear, [[Peripheral Blood Smear]])

Elliptocytes

  • Definition: elliptical RBC’s
  • Etiology
    • Hemolytic Anemia

Leukoerythroblastic Smear

  • Definition: smear with precursor cells of the myeloid and erythroid lineage, which usually indicates the presence of extramedullary hematopoiesis (predominantly in the spleen)
  • Etiology
    • Bone Marrow Infiltration (see Pancytopenia, [[Pancytopenia]])
    • Myelofibrosis/Myelophthisis (see Pancytopenia, [[Pancytopenia]])
    • Severe Stress
      • Blood Loss
      • Hemolysis
      • Infection
  • Features
    • Anisocytosis: RBC’s are of different sizes
    • Immature Myeloid Cells
    • Immature Nucleated RBC’s
    • Megakaryocytic Fragments
    • Poikilocytosis: abnormally-shaped RBC’s
    • Polychromasia (Polychromatophilia): large number of grayish-blue RBC’s, indicative of RBC immaturity
    • Teardrop-Shaped RBC’s (Dacrocytes)

Schistocytes/Helmet Cells

  • Definition: fragmented RBC’s
  • Etiology
    • Thrombotic Thrombocytopenic Purpura (TTP) (see Thrombotic Thrombocytopenic Purpura, [[Thrombotic Thrombocytopenic Purpura]])
    • Hemolytic-Uremic Syndrome (HUS) (see Hemolytic-Uremic Syndrome, [[Hemolytic-Uremic Syndrome]])
    • Mechanical Damage to Red Blood Cells
      • Macroangiopathic Hemolytic Anemia
      • Microangiopathic Hemolytic Anemia (MAHA)

Spur Cells (Acanthocytes)

  • Definition
  • Etiology
    • Spur Cell Anemia

Target Cells (Bell-Shaped Codocytes, Mexican Hat Cells)

  • Definition
  • Etiology
    • Asplenia (see Asplenia, [[Asplenia]]): splenic macrophages normally clear opsonized, deformed, and damaged red blood cells -> if splenic macrophage function is abnormal/absent because due to splenectomy, altered red blood cells will not be removed from the circulation appropriately
      • Auto-Splenectomy Resulting from Sickle Cell Disease (see Sickle Cell Disease, [[Sickle Cell Disease]])
      • Post-Splenectomy
    • End-Stage Liver Disease (ESLD) (see End-Stage Liver Disease, [[End-Stage Liver Disease]]): decreased lecithin/cholesterol acyltransferase (LCAT) activity, resulting in increased cholesterol:phospholipid ratio -> absolute increase in surface area of the red blood cell membrane
    • Hemoglobin C Disease
    • Iron Deficiency Anemia (see Iron Deficiency Anemia, [[Iron Deficiency Anemia]]): decrease in hemoglobin content relative to red blood cell surface area
    • Thalassemias (see Thalassemias, [[Thalassemias]]): decreased hemoglobin content relative to red blood cell surface area
      • Alpha Thalassemia Minor (see Thalassemias, [[Thalassemias]])
      • Beta Thalassemia Minor (see Thalassemias, [[Thalassemias]])

Spherocytes

  • Definition: presence of spherocytes indicates loss of RBC membrane surface area in excess of loss of cell volume -> spherocytes are a feature of many hemolytic anemias
  • Etiology
    • Interaction of Membrane-Antibody Complex with Reticuloendothelial System
      • Autoimmune Hemolytic Anemia (AIHA)
      • Alloimmune Hemolytic Anemia: ABO incompatibility
    • Microangiopathic Hemolytic Anemias (MAHA)
    • Oxidant Injury
    • Phospholipases or Other Membrane Active Enzymes
    • Othe

Clinical Differentiation of Hemolytic Syndromes

hemolyticsyndromes


Clinical Differentiation of Intravascular Hemolysis Syndromes

intravascularhemolysis


Clinical Manifestations

Hematologic Manifestations

  • Iron Deficiency Anemia (see Iron Deficiency Anemia, [[Iron Deficiency Anemia]]): may occur in chronic intravascular hemolysis

Gastrointestinal/Hepatic Manifestations

  • Pigmented (Bilirubin) Gallstones (see Cholelithiasis, [[Cholelithiasis]])

Rheumatologic/Orthopedic Manifestations

  • Skull/Skeletal Deformities: can occur in childhood due to increased hematopoiesis and resultant bone marrow expansion in disorders such as thalassemia

Pulmonary Manifestations

  • Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]]): seen with specific chronic hemolytic anemias

References

  • Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases. Blood 1987;69(3):820 [MEDLINE]
  • Use of trimethoprim-sulfamethoxazole in a glucose-6-phosphate dehydrogenase-deficient population. Rev Infect Dis 1987; 9(Suppl 2):S218-S229 [MEDLINE]
  • A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia. Arch Intern Med 2001; 25;161(12):1529-1533 [MEDLINE]
  • Autoimmune Hemolytic Anemia. Am J Hematol. 2002 Apr;69(4):258-71 [MEDLINE]
  • Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr 2008; 48:63-67 [MEDLINE]
  • Clindamycin-primaquine versus pentamidine for the second-line treatment of Pneumocystis pneumonia. J Infect Chemother 2009; 15(5):343-346 [MEDLINE]
  • Clinical efficacy of first- and second-line treatments for HIV- associated Pneumocystis jirovecii pneumonia. A tri-centre cohort study. J Antimicrob Chemother 2009; 64(6):1282-1290 [MEDLINE]
  • Drug-induced immune haemolytic anaemia in the Berlin Case-Control Surveillance Study.  Br J Haematol   2011; 154:644-653.  Doi: 10.1111/j.1365-2141.2011.08784.x; First published online 12 July 2011 [MEDLINE]