Chapter 13 - Hematology Flashcards
Describe qualitative and quantitative changes in hemoglobin during infancy.
- hemoglobin is high at birth and then declines
- in term infants, it reaches a nadir around 2-3 months of age; in preterm infants, it reaches a nadir after 1-2 months of age
- after birth, HbF is gradually replaced by HbA and disappears by 6-9 months of age
What is a normal reticulocyte count, how is the corrected reticulocyte count determined, what constitutes an appropriate response to anemia?
- normal is 1%
- corrected by taking RC x Hct/45
- 3% corrected is an appropriate response to anemia
What are five diseases that result in a microcytic anemia?
- iron deficiency
- thalassemia
- sideroblastic anemia
- lead toxicity
- chronic disease
Iron Deficiency Anemia
- a microcytic anemia caused by inadequate iron intake or occult blood loss
- nutritional deficiency is more common in those 9-24 months and in adolescent girls whereas occult blood loss is indicative of polyps, Meckle’s, IBD, ulcers, etc.
- presents with the signs and symptoms of anemia plus koilonychia and pica
- labs: low ferritin, high TIBC, low % saturation, low serum iron, elevated erythrocyte protoporphyrin, increased RDW
- treated with ferrous sulfate and vitamin C to enhance intestinal iron absorption; transfusion may be required for severe cases
a-Thalassemia
- deletion of one or more alpha genes on chromosome 16
- 1: asymptomatic
- 2: mild anemia with the cis form more common amongst Asians and the trans more common in Africans
- 3: HbH (B4) disease with severe anemia at birth
- 4: HbBarts (y4) with congestive heart failure and hydrops fetalis
B-Thalassemia Minor
- a mutation of one of the beta genes on chromosome 11
- most common in Mediterraneans and Africans
- largely asymptomatic but may present as a microcytic anemia with target cells and slightly elevated HbA2 and HbF
B-Thalassemia Major
- a mutation of two of the beta genes on chromosome 11
- unpaired alpha chains precipitate and damage RBC membranes, contributing to ineffective hematopoiesis and extravascular hemolysis
- massive erythropoiesis ensues with hepatosplenomegaly, crewcut sign, and chipmunk facies
- labs find a severe microcytic anemia, target cells, elevated HbF, elevated UCB, and elevated LDH
- requires lifelong transfusions and often splenectomy
- hemochromatosis and risk of aplastic crisis are the major complications
Sideroblastic Anemia
- a microcytic anemia due to defective protoporphyrin synthesis
- most commonly caused by an X-linked deficiency of ALA synthase, which converts succinyl-CoA and glycine to ALA
- other causes include lead poisoning, which inhibits ALAD and ferrochelatase; and VitB6 deficiency, secondary to isoniazid treatment, which is a required ALAS cofactor
- iron-laden mitochondria form a ring around the nucleus, which are then called ringed-sideroblasts
- ferritin is high, TIBC is low, serum iron is high, and % saturation is high (all opposite IDA, consistent with iron overload)
What are ringed sideroblasts?
pathologic RBCs found in those with sideroblastic anemia and formed via the excess accumulation of iron in mitochondria
Lead Poisoning
- lead inhibits ferrochelatase and ALA dehydratase, enzymes needed for heme synthesis
- ALA and protoporphyrin accumulate in the blood
- presents with a microcytic, sideroblastic anemia with basophilic stippling, GI and kidney disease
- causes mental deterioration in children (most likely from exposure to lead paint)
- causes headache, memory loss, and demyelination in adults (most likely from exposure to batteries or ammunition)
All megaloblastic anemias have what in common?
- impaired DNA synthesis
- presenting with a macrocytic anemia, hyper-segmented neutrophils, and glossitis
Folate Deficiency Anemia
- a megaloblastic, macrocytic anemia characterized by impaired synthesis of DNA precursors
- caused by poor diet, increased demand, or use of folate antagonists such as methotrexate
- body stores are minimal so deficiency can occur quickly
- presents with a macrocytic anemia, hyper-segmented neutrophils, glossitis, increased homocysteine, and normal methylmalonic acid
B12 Deficiency Anemia
- a megaloblastic, macrocytic anemia
- most often due to pernicious anemia, pancreatic insufficiency, damage to the terminal ileum (Crohn disease or Diphyllobothrium datum), or veganism
- takes a long time to develop since hepatic stores are large
- presents with hyper-segmented neutrophils, glossitis, and demyelination of the spinal cord contributing to poor proprioception, impaired vibratory sensation, and spastic paresis
- labs reveal elevated homocysteine and methylmalonic acid
- treat with money IM vitamin B12 injections
How can folate deficiency anemia be differentiated from B12 deficiency anemia?
- B12 is accompanied by neurologic symptoms
- B12 is characterized by elevated methylmalonic acid while levels are normal in those with a folate deficiency
Describe how B12 is absorbed.
- salivary gland enzymes liberate it
- it is then bound by R-binder and carried through the stomach
- pancreatic proteases in the duodenum detach it from R-binder
- it is then bound by intrinsic factor from gastric parietal cells and the complex is absorbed in the ileum
Hereditary Spherocytosis
- an autosomal dominant defect or deficiency of spectrin, a cytoskeleton-membrane tethering proteins
- this leads to blebs of membrane being lost over time, rending cells round
- those spherocytes are unable to navigate splenic sinusoids and are cleared, resulting in anemia
- RDW and MCHC are elevated since cells get smaller with each bleb that is lost but don’t lose hemoglobin
- presents like other extravascular hemolytic anemias (splenomegaly, pigmented gallstones, jaundice) and an increased risk for aplastic crisis
- diagnosed via elevated reticulocyte count, hyperbilirubinemia, and an osmotic fragility test in which cells are placed in a hypotonic solution
- treat with transfusions until age 5 when splenectomy can be performed with lower risk for severe infection
Hereditary Elliptocytosis
- an autosomal dominant defect in the structure of spectrin
- most cases are asymptomatic but presentation may include normocytic anemia, jaundice, splenomegaly, and gallstones
- elliptical RBCs are found on blood smear
- splenectomy is used to treat symptomatic patients
G6PDH Deficiency
- an X-linked recessive defect that limits production of NADPH and thus glutathione, needed for neutralization of reactive oxygen species
- this leaves cells susceptible to oxidative stress and intravascular hemolysis; usually induced by infection, primaquine, sulfa drugs, dapsone, or fava beans
- presents with hemoglobinuria and back pain hours after exposure; Heinz bodies and bite cells can be seen on a blood smear
- enzyme studies are performed weeks after a hemolytic episode because during the episode, G6PDH-deficient cells are all lysed
What are bite cells and how are they formed?
bite cells are a feature of G6PD deficiency which from when oxidative stress precipitates hemoglobin, forming Heinz bodies which are then removed by splenic macrophages leaving bite cells
What are Heinz bodies? What disease are they associated with? How are they formed? What do they lead to?
- a feature of G6PD deficiency
- form when oxidative stress precipitates hemoglobin (by forming sulfide bonds)
- likely removed by the spleen to form bite cells
What are Howell-Jolly bodies? When are they seen?
they are basophilic nuclear remnants found in RBCs that are normally removed by splenic macrophages but are seen in patients with asplenia or splenic dysfunction
Basophilic stippling of RBCs is indicative of what three pathologies?
- lead poisoning
- sideroblastic anemia (defect in porphyrin metabolism)
- myelodysplastic syndromes
Autoimmune Hemolytic Anemia
- occurs when antibodies are misdirected against RBCs
- may be idiopathic or associated with an underlying disease process (SLE, lymphoma, immunodeficiency)
- classified as fulminant acute type, which presents as acute onset pallor, jaundice, hemoglobinuria, and splenomegaly in infants and younger children after a respiratory infection; recovery is expected
- or as the prolonged type which has a protracted course and high mortality
- labs find severe normocytic anemia, spherocytes, prominent reticulocytosis, leukocytosis, and a positive direct Coombs test
- treated with transfusions and steroids until hemolysis diminishes
Rh Hemolytic Disease
- Rhd mothers exposed to fetal RhD blood (often during delivery) make anti-D IgG
- in subsequent pregnancies this IgG crosses the placenta, causing erythroblastosis fetalis
- presents with severe jaundice, anemia, hepatosplenomegly, hydrops fetalis, and a strongly positive direct Coombs test
- prevented by administration of RhoGAM to Rhd pregnant women during the third trimester
ABO Hemolytic Disease
- anti-A or anti-B IgG from type O mothers crosses the placenta, attacking the fetal erythrocytes
- these antibodies are preformed so it can occur in the first pregnancy and does not worsen in future pregnancies
- presents with mild jaundice in the neonate within 24 hours of birth
- labs find a weakly positive direct Coombs test
- treat with phototherapy