Chapter 13 - Hematology Flashcards

1
Q

Describe qualitative and quantitative changes in hemoglobin during infancy.

A
  • 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
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2
Q

What is a normal reticulocyte count, how is the corrected reticulocyte count determined, what constitutes an appropriate response to anemia?

A
  • normal is 1%
  • corrected by taking RC x Hct/45
  • 3% corrected is an appropriate response to anemia
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3
Q

What are five diseases that result in a microcytic anemia?

A
  • iron deficiency
  • thalassemia
  • sideroblastic anemia
  • lead toxicity
  • chronic disease
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4
Q

Iron Deficiency Anemia

A
  • 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
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5
Q

a-Thalassemia

A
  • 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
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6
Q

B-Thalassemia Minor

A
  • 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
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7
Q

B-Thalassemia Major

A
  • 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
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8
Q

Sideroblastic Anemia

A
  • 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)
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9
Q

What are ringed sideroblasts?

A

pathologic RBCs found in those with sideroblastic anemia and formed via the excess accumulation of iron in mitochondria

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10
Q

Lead Poisoning

A
  • 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)
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11
Q

All megaloblastic anemias have what in common?

A
  • impaired DNA synthesis

- presenting with a macrocytic anemia, hyper-segmented neutrophils, and glossitis

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12
Q

Folate Deficiency Anemia

A
  • 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
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13
Q

B12 Deficiency Anemia

A
  • 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
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14
Q

How can folate deficiency anemia be differentiated from B12 deficiency anemia?

A
  • B12 is accompanied by neurologic symptoms

- B12 is characterized by elevated methylmalonic acid while levels are normal in those with a folate deficiency

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15
Q

Describe how B12 is absorbed.

A
  • 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
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16
Q

Hereditary Spherocytosis

A
  • 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
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17
Q

Hereditary Elliptocytosis

A
  • 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
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18
Q

G6PDH Deficiency

A
  • 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
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19
Q

What are bite cells and how are they formed?

A

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

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20
Q

What are Heinz bodies? What disease are they associated with? How are they formed? What do they lead to?

A
  • a feature of G6PD deficiency
  • form when oxidative stress precipitates hemoglobin (by forming sulfide bonds)
  • likely removed by the spleen to form bite cells
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21
Q

What are Howell-Jolly bodies? When are they seen?

A

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

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22
Q

Basophilic stippling of RBCs is indicative of what three pathologies?

A
  • lead poisoning
  • sideroblastic anemia (defect in porphyrin metabolism)
  • myelodysplastic syndromes
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23
Q

Autoimmune Hemolytic Anemia

A
  • 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
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24
Q

Rh Hemolytic Disease

A
  • 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
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25
Q

ABO Hemolytic Disease

A
  • 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
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26
Q

Microangiopathic Hemolytic Anemia

A
  • a collection intravascular hemolytic anemias
  • includes TTP, HUS, HELLP, and DIC, which all form microthrombi, as well as prosthetic heart valves and aortic stenosis
  • presents the signs and symptoms of anemia and thrombocytopenia
  • schistocytes are a characteristic feature
  • may cause an iron deficiency anemia secondary to hemoglobinuria
27
Q

Hemolytic Uremic Syndrome

A
  • endothelial damage due to drugs or infection (primarily shiga toxin-producing bacteria like E. Coli, O157:H7), results in a pathologic formation of platelet micro thrombi which consumes platelets and shears RBCs
  • presents with renal abnormalities, mucocutaneous bleeding, hemolytic anemia, and schistocytes
  • other findings include thrombocytopenia, increased bleeding time, normal PT/PTT, and increased megakaryocytic
  • treat with plasmapheresis and corticosteroids
28
Q

List five causes of DIC and the reasoning behind each.

A
  • obstetric complication: tissue thromboplastin in the amniotic fluid activates the cascade
  • sepsis: endotoxins trigger cytokine release, which activate the cascade
  • adenocarcinoma: mucin activates the cascade
  • acute promyelocytic anemia: Auer rods trigger coagulation
  • rattlesnake bite
29
Q

Disseminated Intravascular Coagulation

A
  • a pathologic activation of the coagulation cascade which consumes platelets (resulting in mucocutaneous bleeding) and induces widespread microthrombi formation (resulting in ischemia and infarction)
  • causes range from obstetric complications (tissue thromboplastin in amniotic fluid activates the cascade), sepsis (endotoxins induce endothelial cells to make tissue factor), adenocarcinoma (mucin activates cascade), acute promyelocytic leukemia (Auer rods induce coagulation), or rattlesnake bite
  • in contrast to HUS/TTP, these microthrombi are platelet and fibrin-rich
  • the best screening test is elevated D-dimers, but there is also a thrombocytopenia, elevated PT and PTT, diminished fibrinogen, and a hemolytic anemia with schistocytes
  • treat with cryo
30
Q

Describe the symptoms of sickle cell disease.

A
  • extravascular hemolysis: jaundice, gall stones, anemia, splenomegaly
  • intravascular hemolysis: target cells, decreased haptoglobin
  • increased erythropoiesis: hepatosplenomegaly and crew cut sign
  • vast-occlusion: dacylitis, autosplenectomy (infection with encapsulated organisms, risk of Salmonella paratyphi osteomyelitis, Howell-Jolly bodies), acute chest syndrome (precipitated by pneumonia which slows transit time via vasodilation and presents with SOA, chest pain, lung infiltrates), MSK pain crisis including dactylytis, renal papillary necrosis resulting in hematuria and proteinuria, stroke, and priapism
  • impaired growth secondary to poor pulmonary function, endocrine abnormalities, chronic anemia, and pain crises
  • splenic sequestration preventing with pallor, fatigue, irritability, splenomegaly, and shock
31
Q

Describe the pathophysiology of Sickle Cell disease.

A
  • an autosomal recessive Glu to Val mutation in the beta globin chain creates a hydrophobic pocket for polymerization
  • HbS polymerizes when deoxygenated, particularly with hypoxemia, dehydration, acidosis, or increased transit time
  • sickling causes membrane damage leading to predominately extravascular hemolysis but some intravascular
  • sickling also increases resistance to flow through microvasculature, leading to tissue hypoxia, pain, and tissue damage
  • hepatosplenomegaly and bone marrow expansion follow the anemia
32
Q

Which hemoglobin patterns in a newborn are consistent with sickling disorders?

A
  • FS
  • FSA
  • FSC
33
Q

What are the two most common surgeries in children with sickle cell disease?

A
  • tonsillectomy

- cholecystectomy

34
Q

Why are children with sickle cell disease started on penicillin prophylaxis?

A

to prevent sepsis, pneumococcal sepsis in particular, given their decreased splenic function and susceptibility to encapsulated organisms

35
Q

What are three causes of anemia in those with sickle cell disease?

A
  • hemolytic anemia
  • splenic sequestration
  • parvovirus-induce aplastic crisis
36
Q

What is a transcranial doppler and why is it used to manage patients with sickle cell disease?

A
  • it evaluates cerebral blood-vessel flow
  • making it a useful screening tool to predict the risk of patients for stroke
  • stroke occurs in approximately 10% of children with sickle cell disease
37
Q

Patients with sickle cell disease have what additional immunization recommendations?

A
  • the PCV23 polysaccharide vaccine at 2 and 5 years old

- MCV at 2 with a booster 3-5 years later

38
Q

What is acute chest syndrome, how does it present, and how should it be treated?

A
  • a term used to describe pneumonia, intrapulmonary sickling, or pulmonary fat embolism in a patient with sickle cell disease
  • presents with fever, cough, difficulty breathing, chest pain, and decreased oxygenation; CXR usually finds multilobar infiltrates, effusions, atelectasis
  • managed with IV fluids, oxygen supplementation, incentive spirometry, RBC transfusion, control of pain, and antibiotics if there is pneumonia
39
Q

What type of transfusion should sickle cell patients receive and why?

A
  • erythrocytapheresis, also known as exchange transfusion
  • it is an automated method of doing an exchange transfusion and is the best way to rapidly lower HbS and raise HbA
  • using simple transfusion would increase blood viscosity and could worsen vaso-occlusive crises
  • reserved for severe respiratory distress, failing pulmonary function, or acute onset of stroke
40
Q

What preventative care is indicated for patients with sickle cell disease?

A
  • hydroxyurea to increase HbF
  • daily oral penicillin prophylaxis to decrease the risk of S. pneumoniae sepsis
  • daily folic acid
  • the PCV23 polysaccharide vaccine at 2 and 5 years old; MCV at 2 with a booster 3-5 years later
  • serial transcranial Doppler ultrasound beginning at 2 years of age to identify those are risk for stroke
41
Q

Fanconi Anemia

A
  • an autosomal recessive congenital aplastic anemia caused by a DNA repair defect
  • results in bone marrow failure
  • presents with a non-hemolytic normocytic anemia, pancytopenia, petechiae and ecchymosis, short stature, cafe-au-lait spots, and thumb/radial defects
  • importantly, reticulocyte count is low
  • treat with transfusions and bone marrow transplant
42
Q

Diamond-Blackfan Anemia

A
  • also known as congenital hypoplastic anemia
  • it is autosomal recessive or autosomal dominant and caused by congenital erythroid aplasia
  • presents with rapid onset anemia in the first year of life; craniofacial, renal and cardiac anomalies; short stature; and triphalangeal thumbs
  • labs reveal a macrocytic anemia with reticulocytopenia and normal platelets
  • treat with corticosteroids and transfusions
43
Q

Transient Erythroblastopenia of Childhood

A
  • an anemia that begins after 1 year of age with a slow onset
  • the cause is unknown
  • labs reveal low hemoglobin, low reticulocyte count, normal platelet count, and fewer RBC precursors in marrow
  • spontaneous recovery generally occurs within several weeks without treatment
44
Q

Parvovirus B19-Associated Pure Red Cell Aplasia

A
  • an anemia caused by parvo B19
  • often preceded by a URI and “slapped cheeks” rash of fifth disease, but the anemia is generally asymptomatic unless patients are already susceptible to aplastic crisis
  • hemoglobin and reticulocytes are diminished but platelet count is normal
  • spontaneous recovery generally occurs within 2 weeks although RBC transfusions may be required for patients with sickle cell disease
45
Q

What is the difference between primary and secondary polycythemia?

A

primary is a malignancy and rare in childhood, whereas secondary, which can be further classified as appropriate or inappropriate, is caused by increased erythropoietin production and is more common in childhood

46
Q

Secondary Polycythemia

A
  • an increase in RBCs relative to total volume due to an increase in EPO production
  • can be classified as appropriate if caused by chronic hypoxemia (cyanotic congenital heart disease, pulmonary disease, residence at high altitudes) or as inappropriate
  • presents with dizziness, blurry vision, headache, flushed face due to congestion, and itching, especially after bathing (due to histamine release from excess mast cells)
  • may be further complicated by thrombosis or bleeding
  • labs reveal elevated hemoglobin and hematocrit but normal platelets and WBC
  • treat with management of the underlying condition and phlebotomy as necessary
47
Q

Hemophilia A

A
  • an X-linked recessive FVIII deficiency
  • can be classified as mild, moderate, or severe based on the serum activity of FVIII (>5%, 1-5%, <1%, respectively)
  • presents with deep bleeding and post-surgical bleeding; bleeding into the iliopsoas is a feared complication due to delayed recognition and the potential for significant blood loss
  • PTT is elevated but corrected by 1:1 mixing; platelet count, PT, and bleeding time are normal
  • can be treated with desmopressin, which increases release of stored FVIII
48
Q

von Willebrand’s Disease

A
  • the most common inherited coagulation disorder
  • a genetic qualitative or quantitative vWF deficiency (type I is partial quant, type II is qual, type III is complete quant)
  • it presents with mucocutaneous bleeding that varies from generation to generation
  • labs reveal increased bleeding time, an increased PTT, and an abnormal risocetin test
  • treat with desmopressin, which increases the release of vWF from endothelial cells; may require cryoprecipitate for serious bleeding, extensive surgeries, or type III disease
49
Q

Hemophilia B

A
  • an X-linked recessive FIX deficiency
  • presents with deep bleeding and post-surgical bleeding
  • PTT is elevated but corrected by 1:1 mixing; platelet count, PT, and bleeding time are normal
  • treated with FIX replacement
50
Q

Vitamin K is necessary for what coagulation factors to function?

A
  • FII, FVII, FIX, FX

- Proteins C and S

51
Q

Vitamin K Deficiency

A
  • may be due to newborn-status or long-term antibiotics, which limit gut flora; medications; pancreatic insufficiency, biliary obstruction, or prolonged diarrhea
  • presents with bruising and bleeding; hemorrhagic disease of the newborn is uniquely characterized by serious bleeding, often into the brain
  • labs demonstrate prolonged PT and PTT
  • treated with administration of vitamin K and fresh frozen plasma as needed
52
Q

What is hereditary hemorrhagic telangiectasia?

A

an autosomal dominant disorder of blood vessels that results in locally dilated and tortuous veins and capillaries in the skin and mucous mebranes

53
Q

Thrombocytopenia-Absent Radius Syndrome

A
  • an autosomal recessive condition
  • characterized by thrombocytopenia and limb abnormalities, particularly absence of the radius
  • thrombocytopenia improves in the second or third year of life
54
Q

Immune-Mediated Thrombocytopenia

A
  • the most common cause of thrombocytopenia
  • plasma cells in the spleen produce autoantibodies to platelet antigens, particularly GPIIb-IIIa, and these antibody-bound platelets are cleared by splenic macrophages
  • can be divided into an acute form, seen more commonly in children weeks after a viral infection or immunization, and a chronic form, seen more commonly in adults, which lasts more than 6 months
  • the chronic form is particularly common amongst women of childbearing age and ITP in the mother may induce a short-lived thrombocytopenia in offspring as the IgG crosses the placenta
  • presents with normal PT/PTT, thrombocytopenia, increased megakaryocytic on bone marrow biopsy
  • treat with corticosteroids, IVIG, or splenectomy
55
Q

What are the two types of neonatal immune-mediated thrombocytopenia?

A
  • passive autoimmune thrombocytopenia in newborns of mothers affected by chronic ITP; antibodies cross the placenta and destroy fetal/newborn platelets
  • alloimmune thrombocytopenia when mother produces antibodies against a paternal platelet antigen, which then cross the placenta and destroy fetal/newborn platelets
56
Q

Glanzmann’s Thrombasthenia

A
  • an autosomal recessive GPIIb-IIIA deficiency that impairs platelet aggregation
  • fibrinogen binding is impaired but vWF binding is intact, so a risocetin test will be normal
57
Q

Bernard-Soulier Syndrome

A
  • an autosomal recessive GPIb-IX deficiency that impairs platelet adhesion
  • presents with a mild thrombocytopenia (because poorly functioning platelets are removed) as well as slightly enlarged platelets (because immature ones are being released - B-S = “Big Suckers”)
  • risocetin test will be abnormal because the platelets can’t bind vWF well
58
Q

List four qualitative platelet disorders.

A
  • Bernard-Soulier syndrome (GPIb-IX deficiency)
  • Glanzmann Thromboasthenia (GPIIb-IIIa deficiency)
  • Aspirin (impairs TXA2 formation)
  • Uremia (impairs adhesion and aggregation)
59
Q

Protein C/S Deficiency

A
  • an autosomal dominant condition which results in less inactivation of FV and FVIII, leading to a hypercoagulable state
  • homozygotes typically experience purpura fulminant, a nonthrombocytopenic purpura, with shock, fever, and rapidly spreading skin bleeding
  • heterozygotes present later in life with deep venous or CNS thrombosis
  • increases the risk for warfarin skin necrosis because warfarin already results in a temporary deficiency of C and S relative to factors II, VII, IX, and X
  • treated with anticoagulation therapy and fresh frozen plasma
60
Q

Factor V Leiden Mutation

A
  • a mutated form of FV which lacks the cleavage site for deactivation by proteins C and S
  • the most common inherited cause of hyper coagulable state
61
Q

What is the most common cause of neutropenia during childhood?

A

infection, because this may suppress the bone marrow, marginate neutrophils, or exhaust marrow reserves

62
Q

Chronic Benign Neutropenia of Childhood

A
  • a noncyclic neutropenia common in children under age 4 without any other abnormalities
  • most children have increased incidence of mild infections but hav otherwise normal appearance and growth
  • usually resolves spontaneously in months to years
63
Q

Kostmann Syndrome

A
  • a severe autosomal recessive congenital agranulocytosis

- presents with frequent and life-threatening pyogenic bacterial infections beginning in infancy

64
Q

Schwachman-Diamond Syndrome

A

exocrine pancreatic insufficiency with malabsorption, metaphysical chrondrodysplasia leading to short stature, and neutropenia, presenting with failure to thrive and recurrent infections