Trauma, GI hemorrhage (may be occult) are common causes; less common are genitourinary sources (menorrhagia, gross hematuria), internal bleeding such as intraperitoneal from spleen or organ rupture, retroperitoneal, iliopsoas hemorrhage (e.g., in hip fractures). Acute bleeding is associated with manifestations of hypovolemia, reticulocytosis, macrocytosis; chronic bleeding is associated with iron deficiency, hypochromia, microcytosis.
Causes are listed in Table 62-3.
TABLE 62-3CLASSIFICATION OF HEMOLYTIC ANEMIASa ||Download (.pdf) TABLE 62-3CLASSIFICATION OF HEMOLYTIC ANEMIASa
| ||Intracorpuscular Defects ||Extracorpuscular Factors |
|Hereditary || |
|Familial (atypical) hemolytic uremic syndrome |
|Acquired ||Paroxysmal nocturnal hemoglobinuria (PNH) || |
Mechanical destruction (microangiopathic)
Intracellular RBC abnormalities: most are inherited enzyme defects [glucose-6-phosphate dehydrogenase (G6PD) deficiency > pyruvate kinase deficiency], hemoglobinopathies, sickle cell anemia and variants, thalassemia, unstable hemoglobin variants.
G6PD deficiency: leads to episodes of hemolysis precipitated by ingestion of drugs that induce oxidant stress on RBCs. These include antimalarials (chloroquine), sulfonamides, analgesics (phenacetin), and other miscellaneous drugs (Table 62-4).
Sickle cell anemia: characterized by a single-amino-acid change in β globin (valine for glutamic acid in the 6th residue) that produces a molecule of decreased solubility, especially in the absence of O2. Although anemia and chronic hemolysis are present, the major disease manifestations relate to vasoocclusion from misshapen sickled RBCs. Infarcts in lung, bone, spleen, retina, brain, and other organs lead to symptoms and dysfunction (Fig. 62-2).
Membrane abnormalities (rare): spur cell anemia (cirrhosis, anorexia nervosa), paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis (increased RBC osmotic fragility, spherocytes), hereditary elliptocytosis (causes mild hemolytic anemia).
Immunohemolytic anemia (positive Coombs’ test, spherocytes). Two types: (a) warm antibody (usually IgG): idiopathic, lymphoma, chronic lymphocytic leukemia, systemic lupus erythematosus, drugs (e.g., methyldopa, penicillins, quinine, quinidine, isoniazid, sulfonamides); and (b) cold antibody—cold agglutinin disease (IgM) due to Mycoplasma infection, infectious mononucleosis, lymphoma, idiopathic; paroxysmal cold hemoglobinuria (IgG) due to syphilis, viral infections.
Mechanical trauma (macro- and microangiopathic hemolytic anemias; schistocytes): prosthetic heart valves, vasculitis, malignant hypertension, eclampsia, renal graft rejection, giant hemangioma, scleroderma, thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, disseminated intravascular coagulation, march hemoglobinuria (e.g., marathon runners, bongo drummers).
Direct toxic effect: infections (e.g., malaria, Clostridium perfringens toxin, toxoplasmosis).
Hypersplenism (pancytopenia may be present).
TABLE 62-4DRUGS THAT CARRY RISK OF CLINICAL HEMOLYSIS IN PERSONS WITH G6PD DEFICIENCY ||Download (.pdf) TABLE 62-4DRUGS THAT CARRY RISK OF CLINICAL HEMOLYSIS IN PERSONS WITH G6PD DEFICIENCY
Pathophysiology of sickle cell crisis.
Elevated RI, polychromasia and nucleated RBCs on smear; also spherocytes, elliptocytes, schistocytes, or target, spur, or sickle cells may be present depending on disorder; elevated unconjugated serum bilirubin and LDH, elevated plasma hemoglobin, low or absent haptoglobin; urine hemosiderin present in intravascular but not extravascular hemolysis, Coombs’ test (immunohemolytic anemias), osmotic fragility test (hereditary spherocytosis), hemoglobin electrophoresis (sickle cell anemia, thalassemia), G6PD assay (best performed after resolution of hemolytic episode to prevent false-negative result).
TREATMENT: ANEMIA GENERAL APPROACHES
The acuteness and severity of the anemia determine whether transfusion therapy with packed RBCs is indicated. Rapid occurrence of severe anemia (e.g., after acute GI hemorrhage resulting in Hct <25%, following volume repletion) or development of angina or other symptoms is an indication for transfusion. Hct should increase 3–4% [Hb by 10 g/L (1 g/dL)] with each unit of packed RBCs, assuming no ongoing losses. Chronic anemia (e.g., vitamin B12 deficiency), even when severe, may not require transfusion therapy if the pt is compensated and specific therapy (e.g., vitamin B12) is instituted. SPECIFIC DISORDERS
Iron deficiency: find and treat cause of blood loss, oral iron (e.g., FeSO4 300 mg tid).
Folate deficiency: common in malnourished, alcoholics; less common now than before folate food supplementation; folic acid 1 mg PO qd (5 mg qd for pts with malabsorption).
Vitamin B12 deficiency: can be managed either with parenteral vitamin B12 100 μg IM qd for 7 d, then 100–1000 μg IM per month or with 2 mg oral crystalline vitamin B12 per day. An inhaled formulation is also available.
Anemia of chronic disease: treat underlying disease; in uremia use recombinant human erythropoietin, 50–150 U/kg three times a week; role of erythropoietin in other forms of anemia of chronic disease is less clear; response more likely if serum erythropoietin levels are low. Target Hb 9–10 g/dL. Iron administration is not useful.
Sickle cell anemia: hydroxyurea 10–30 mg/kg per day PO increases level of Hemoglobin F (HbF) and prevents sickling, treat infections early, supplemental folic acid; painful crises treated with oxygen, analgesics (opioids), hydration, and hypertransfusion; consider allogeneic bone marrow transplantation in pts with increasing frequency of crises.
Thalassemia: transfusion to maintain Hb >90 g/L (>9 g/dL), folic acid, prevention of Fe overload with deferoxamine (parenteral) or deferasirox (oral) chelation; consider splenectomy and allogeneic bone marrow transplantation.
Aplastic anemia: antithymocyte globulin and cyclosporine leads to improvement in 70%, bone marrow transplantation in young pts with a matched donor.
Autoimmune hemolysis: glucocorticoids, sometimes immunosuppressive agents, danazol, plasmapheresis, rituximab.
G6PD deficiency: avoid agents known to precipitate hemolysis.
For a more detailed discussion, see Adamson JW: Iron Deficiency and Other Hypoproliferative Anemias, Chap. 126, p. 625; Benz EJ: Disorders of Hemoglobin, Chap. 127, p. 631; Hoffbrand AV: Megaloblastic Anemias, Chap. 128, p. 640; Luzzato L: Hemolytic Anemias and Anemia Due to Acute Blood Loss, Chap. 129, p. 649; and Young NS: Bone Marrow Failure Syndromes Including Aplastic Anemia and Myelodysplasia, Chap. 130; p. 662 in HPIM-19.