Quick Compendium Chapter 4 Misc Disorders

Front 1

Congenital dyserythropoietic anemia (CDA)
1. most common type?
2. inheritance?
3. smear findings?
4. serum findings?
5. alternate name?

Back 1

1. type II
2. autosomal recessive
3. multinucleate erythroid precursors
4. positive acidified serum (Ham)
5. hereditary erythroblast multinuclearity with positive acidifed serum (HEMPAS)

Front 2

Difference between positive Ham test in CDA type II and PNH?

Back 2

CDA type II lysis with heterologous serum ONLY (due to abnormally high RBC i antigen)
PNH lysis with autologous and heterolgous serum

Front 3

Paroxysmal nocturnal hematuria (PNH)
1. inheritance?
2. level of defect?
3. molecular defect?
4. associated gene mutation?

Back 3

1. Acquired clonal disorder
2. hematopoietic stem cell
3. single defect, decreased glycosyl phosphatidyl inositol (GPI) anchors
4. PIG-A

Front 4

T/F PNH only affects red cell populations.

Back 4

False- defective hematopoietic stem cell clone dominates red cell population and eventually variable proportions of white cells and platelets

Front 5

Glycosyl phosphatidyl inositol anchors
1. function?
2. gene encoded on?
3. gene location?

Back 5

1. attaches array of proteins to cell surface, many of which deflect immune system destruction
2. on phosphatidyl inositol glycan class A (PIG-A) gene, initial step of synthesis
3. X chromosome

Front 6

PNH
1. classic clinical presentation
2. finding of red cell indices?
3. long term complications?

Back 6

1. episodic hemolysis, especially at night (classic, not usual)
2. chronic normocytic, normochromic anemia
3. thrombo- and leukopenias, eventually may evolve to aplastic anemia and/or AML

Front 7

What are the characteristic abnormalities of RBCs in PNH?

Back 7

diminished cell-surface decay-accelerating factor (DAF, CD55), decreased membrane inhibitor of reactive lysis (MIRL, CD59), decreased acetylcholinesterase (AchE), decreased CD16, and decreased CD48

Front 8

Phenotype of RBCs in PNH?

Back 8

hypersensitivity to complement mediated lysis

Front 9

1. How is sucrose hemolysis test performed?
2. Positive test indicates?

Back 9

1. incubate patient's RBCs in serum and isotonic sucrose (promotes complement binding)
2. increased hemolysis (positive test) compared to control indicates PNH

Front 10

1. How is acidified serum (Ham) test performed?
2. positive test indicates?

Back 10

1. incubate RBCs in heterologous and homologous serum that's been acidified (activating complement)
2. enhanced hemolysis in both sera consistent with PNH (heterologous only indicates CDA type II)

Front 11

Flow cytometry findings in PNH?

Back 11

decreased CD59 and CD55 on RBCs, leukocytes and platelets. Serial studies show expansion of abnormal populations with disease progression

Front 12

PNH
1. T/F leukocyte alkaline phosphatase is decreased

Back 12

1. True

Front 13

What are bone marrow findings in PNH?

Back 13

early in disease hypercellular, evolution to aplastic anemia and/or AML is common

Front 14

Name group of disorders unified by anemia and ringed sideroblasts in the bone marrow aspirate?

Back 14

Sideroblastic anemia

Front 15

What are typical peripheral smear findings in sideroblastic anemia?

Back 15

hypochromic anemia (maybe micro-, normo-, or macrocytic)
basophilic stippling may be present (due to overstaining of iron-containing Pappenheimer bodies)

Front 16

Difference in red cell indices for acquired vs. hereditary sideroblastic anemia?

Back 16

Acquired more likely macrocytic
Inherited more likely microcytic

Front 17

T/F Classic finding in sideroblastic anemia is a bimodal red cell volume distribution

Back 17

True

Front 18

What are the characteristic iron studies in sideroblastic anemia?

Back 18

Elevated serum iron, high transferrin percent saturation, high ferritin

Front 19

Why is there often hyperbilirubinemia, high LDH, and decreased serum haptoglobin in sideroblastic anemia?

Back 19

Intramedullary hemolysis associated with ineffective erythropoiesis

Front 20

Causes of acquired sideroblastic anemia?

Back 20

-Clonal stem cell defects/myelodysplasia (refractory anemia with ringed sideroblasts) VAST MAJORITY OF CASES
-Meds (isoniazid, chloramphenicol, chemo)
-irradiation
-alcohol
-copper deficiency (rare)

Front 21

What is Pearson syndrome?

Back 21

sideroblastic anemia with pancreatic insufficiency This is a rare form of acquired sideroblastic anemia

Front 22

Typical presentation of acquired sideroblastic anemia?

Back 22

Older adults with macrocytic, hypochromic anemia. Marrow aspirate shows >15% ringed sideroblasts. Cytogenetic anomalies in 25-50% of cases

Front 23

Inherited sideroblastic anemia
1. mode of inheritance?
2. responsible gene?
3. typical presentation?

Back 23

1. X linked recessive
2. ALAS2, large number of mutations found
3. childhood, organ dysfunction due to iron overload, low MCV, high RDW (may have bimodal distribution)

Front 24

2 causes of acquired pure red cell aplasia?

Back 24

thymoma and parvo B19 infection

Front 25

Cause of congenital pure red cell aplasia?

Back 25

Blackfan-Diamond syndrome

Front 26

Name disorder that causes transient arrest in RBC production, lasts about 2 weeks, usually barely noticed in healthy children and adults but can be catastrophic in those with chronic hemolytic anemia?

Back 26

Parvo B19 infection

Front 27

Mechanism of parvo B19 infection and marrow findings?

Back 27

Infects erythroid progenitor cells, marrow exam shows numerous giant pronormoblasts, reduced mature forms, and viral nuclear inclusions

Front 28

At what stage are erythroid precursors arrested when infected with parvo B19?

Back 28

pronormoblast stage

Front 29

Transient erythrocytopenia of childhood (TEC)
1. Define
2. peripheral smear findings
3. marrow findings

Back 29

1. Self limiting disorder arising in kids 1-4 years old previously healthy, temporary arrest of erythropoiesis
2. reticulocytopenia, normochromic, normocytic anemia
3. hypocellular with erythroid hypoplasia

Front 30

1. What is Blackfan-Diamond syndrome?
2. T/F platelets and leukocytes are also affected?
3. marrow findings
4. treatment

Back 30

1. -congenital pure red cell aplasia
-rare, constitutional disease
-usually evident by age 5
2. False
3. Erythroid precursors low or absent
4. corticosteroids (~75% response rate)

Front 31

1. What antigen is overexpressed on red cells in Blackfan-Diamond syndrome?

Back 31

i antigen

Front 32

T/F Fetal hemoglobin is decreased in Blackfan-Diamond syndrome?

Back 32

False - it is increased (in contrast to transient erythrocytopenia of childhood)

Front 33

Acquired pure red cell aplasia
1. Affects what population?
2. Over half associated with what condition?
3. Other associated conditions?

Back 33

1. Usually adults
2. Thymoma (esp. spindle cell/medullary type)
3. collagen vascular disease, lymphoproliferative disorders of large granular lymphocytes, meds

Front 34

Acquired pure red cell aplasia increasingly seen with what kind of medical therapy?

Back 34

Erythropoietin therapy, anti-Epo antibodies detected in many cases

Front 35

Name 6 inherited disorders associated that may lead to aplastic anemia

Back 35

Fanconi anemia, dyskeratosis congenita, Schwachman-Diamond syndrome, reticular dysgenesis, Down syndrome, and familial aplastic anemia

Front 36

Name 3 inherited disorders associated with aplasia of single cell lines and the associated cell line

Back 36

Kostman syndrome (neutropenia), Blackfan-Diamond syndrome (anemia), and thrombocytopenia-absent radii (TAR) syndrome (thrombocytopenia)

Front 37

Fanconi anemia (FA)
1. mode of inheritance?
2. type of chromosomal disorder?

Back 37

1. autosomal recessive
2. chromosomal breakage

Front 38

What congenital anomalies are associated with Fanconia anemia?

Back 38

They are (often first manifestations): abnormal skin pigmentation, skeletal anomalies, renal anomalies, short stature, micophthalmia, and mental retardation.
Up to 1/3 display none of these

Front 39

What skin pigmentation disorders are associated with Fanconi anemia?

Back 39

cafe au lait spots, hypo- and hyperpigmentation

Front 40

What skeletal abnormalities are associated with Fanconi anemia?

Back 40

Abnormal radii, hypoplastic thumb, scoliosis

Front 41

What renal disorders are associated with Fanconi anemia?

Back 41

horseshoe kidney

Front 42

What's the initial clinical course of most patients with Fanconi anemia?

Back 42

aplastic anemia develops in most patients by age 10. Often isolated anemia (or thrombocytopenia) before aplastic anemia

Front 43

What are long term complications of Fanconi anemia?

Back 43

Marrow failure or clonal hematopoietic defects including AML (M4 or M5) and MDS

Front 44

What epithelial malignancies have an increased incidence in Fanconi anemia?

Back 44

Cutaneous malignancies, hepatocellular carcinoma, gastric carcinoma and others

Front 45

What are the diagnostic cytogenetic findings in Fanconi anemia?

Back 45

-increased propensity for spontaneous chromosomal breakage
- particularly hypersensitive to clastogenic agents such as diepoxybutane and mitomycin C, requires altered preconditioning prior to bone marrow transplant

Front 46

Name 5 chromosomal breakage syndromes

Back 46

Fanconi anemia, xeroderma pigmentosum (XP), ataxia telangiectasia (TA), Bloom syndrome (BS), and Cockayne syndrome

Front 47

Hemoglobin S
1. defect?
2. found in parts of the world where what infection is prevalent?
3. prevalence of trait among African Americans?

Back 47

1. beta6 glu --> by valine
2. falciparum malaria
3. about 10%

Front 48

What hemoglobin disorders have similar clinical manifestations to sickle cell disease?

Back 48

sickle cell beta 0 thalassemia, SC disease (HbSC), and sickle cell beta + thalassemia

Front 49

1. What causes red cells to sickle?
2. Average life span of a sickled RBC?

Back 49

1. abnormal polymerization of deoxygenated hemoglobin S
2. 17 days (normal is 120 days)

Front 50

What are the hemoglobin electrophoresis findings in sickle cell disease?

Back 50

>80% HbS, 1-20% HbF, 1-4% HbA2, and 0% HbA

Front 51

What disorders show sickled red cell on peripheral smear?

Back 51

Hgb SS, S- beta thalassemia, S-C, S-D, and C Harlem

Front 52

What test is based on the principle that metabisulfate promotes Hb deoxygenation?

Back 52

metabisulfite sickling test, positive in hemoglobin SS disease

Front 53

What's the mechanism of the Sickledex test?

Back 53

aka dithionate solubility test, lysed RBCs incubated with dithionate that precipates HbS, positive in SS disease

Front 54

At what age is sickle cell disease usually clinically apparent and why?

Back 54

Usually at 6 months of age when HbF decreases and HbS levels increase beyond 50%

Front 55

What hemoglobin disorder is characterized by chronic hemolytic anemia and recurrent crises?

Back 55

sickle cell disease

Front 56

What coagulation abnormality contributes to the clinical expression of sickle cell?

Back 56

Thrombosis

Front 57

Aplastic crises in sickle cell
1. etiology
2. what are the clinical characteristics?
3. duration?
4. level of anemia?

Back 57

1. transient arrest of erythropoiesis
2. abrupt drop in Hgb, reticulocytes, and red cell precursors in the marrow
3. usually only a few days
4. can be severe

Front 58

What infection is responsible for nearly 70% of aplastic crises in children with sickle cell?

Back 58

Parvovirus B19

Front 59

Splenic sequestration in sickle cell
1. clinical presentation?
2. often associated with?
3. who is most susceptible?

Back 59

1. enlarged, tender spleen
2. viral illness
3. children and adults with SC disease or sickle cell beta + thalassemia

Front 60

What may cause worsening of anemia in SS patients that progresses more slowly than aplastic crisis or splenic sequestration?

Back 60

Progressive renal insufficiency (with decreasing erythropoietin) or supervening iron/folate/B12 deficiency

Front 61

What is a hyperhemolytic crisis?

Back 61

Sudden exacerbation anemia in SS with profound reticulocytosis and hyperbilirubinemia. Has been associated with G6PD deficiency.

Front 62

Acute pain crises in SS
1. etiology
2. possible precipitating factors?

Back 62

1. vasooclusive events within the bone
2. exposure to cold, dehydration, infection, or alcohol consumption

Front 63

Acute chest syndrome in SS
1. clinical presentation?
2. possible etiologies?

Back 63

1. dyspnea, cough, chest pain, and fever. May find tachypnea, leukocytosis, pulmonary infiltrate on chest xray, and progressive hypoxia
2. vasoocclusive events or bacterial pneumonia

Front 64

Why are infections a major source of morbidity and mortality in sickle cell disease and what infections are most common?

Back 64

Functional asplenia makes infections worse. S. pneumoniae infections are the most common overall, other common infections include Salmonella, Haemophilus and M. pneumoniae

Front 65

Neurologic complications are frequent in SS disease. What are common manifestations?

Back 65

TIAs, cerebral infarcts, cerebral hemorrhage, cord infarction, sensorineural hearing loss, and meningitis

Front 66

1/3 of patient with SS disease will have angiographic appearance of what disease due to neurologic complications?

Back 66

Moyamoya disease (segmental arterial stenoses with 'puff of smoke' collaterals

Front 67

Common presentation of acute hepatic crisis in sickle cell disease?

Back 67

aka right upper quadrant syndrome, presents as progressive jaundice, elevated LFTs, and a tender enlarged liver, usually resolves within 2 weeks but may progress to liver failure

Front 68

Common chronic liver problems seen in SS disease?

Back 68

Chronic nonspecific hepatomegaly and liver dysfunction (probably related to centrilobular congestion), chronic Hep C, pigmented gallstones

Front 69

What are some pregnancy related complications in SS disease?

Back 69

Increased rate of maternal and fetal deaths, increased preeclampsia, increased IUGR, intrauterine fetal demise and prematurity

Front 70

Name the 7 classic sickle cell nephropathies

Back 70

gross hematuria, papillary necrosis, nephrotic syndrome, renal infarction, isosthenuria, pyelonephritis, and renal medullary carcinoma (also increased in sickle cell trait and SC disease)

Front 71

T/F Occular complications (proliferative retinopathy) occurs with same frequency in SS, SC and sickle beta + thalassemia

Back 71

False, greater rates in SC and sickle beta + thalassemia than SS

Front 72

What is a common complication of SS that may affect the vertebrae, hands, feet, and femoral and humeral heads ?

Back 72

osteonecrosis

Front 73

Sickle cell trait (SA)
1. clinical presentation?
2. peripheral smear findings?
3. characteristic hemoglobin electrophoresis findings?
4. screening test results?

Back 73

1. usually asymptomatic
2. no sickle cells
3. 35 to 45% HbS, 1% HbF, 1-3% HbA2, 50-55% HbA
4. positive metabisulfite and dithionate tests

Front 74

S-alpha-thalassemia
1. what is it?
2. HbS is increased or decreased and why?

Back 74

1. when alpha thalassemia is coinherited with sickle cell trait
2. HbS is decreased, degree to which relative to number of alpha globin genes deleted

Front 75

S-beta-thalassemia
1. what is it?
2. HbS is increased or decreased?
3. mild, intermediate, or severe disease?

Back 75

1. when beta thalassemia is coinherited with sickle cell trait
2. increased (usually >50%)
3. severe depending upon type of beta thalassemia defect

Front 76

Hemoglobin SC disease
1. what is it?
2. HbS levels?
3. mild, intermediate, or severe disease?

Back 76

1. heterozygosity for HbS and HbC
2. ~50%
3. intermediate severity between SS and SA

Front 77

Hemoglobin SC disease
1. average red cell life span?
2. which complications occur at about same rate as in SS disease?
3. peripheral smear findings?

Back 77

1. 27 days
2. avascular necrosis of bone and proliferative retinopathy (others about half as frequent
3. mild sickling and abundant target cells

Front 78

Hemoglobin A2 prime (HbA2')
1. what is it?
2. T/F it is best detected by gel electrophoresis

Back 78

1. clinically insignficant delta-chain variant, occurs in 1-2% of African Americans
2. False, best detected by HPLC

Front 79

1. Why can HbA2' lead to underdiagnosis of beta thalassemia trait?
2. How can calculations be adjusted to account for the answer to 1?

Back 79

1. A2' barely detectable on gel electrophoresis
2. HbA2 and HbA2' levels must be added

Front 80

HbC
1. mutation?
2. hemoglobin findings in trait (heterozygous AC)?
3. clinical presentation?
4. peripheral smear findings

Back 80

1. beta6 glu --> lys
2. 40-50% Hgb in the C band (HbA2 = HbC
3. generally asymptomatic
4. scattered target cells

Front 81

Hemoglobin C disease (homozygous CC)
1. hemoglobin findings?
2. clinical presentation?
3. peripheral smear findings?

Back 81

1. 90% HbC, 7% HbF, 3% HbA2, 0% HbA
2. mild hemolytic anemia, splenomegaly
3. numerous target cells, hexagonal or rod shaped crystals may be found in red cells, esp after splenectomy

Front 82

HbE
1. point mutation?
2. geographical prevalence?
3. CBC findings?
4. peripheral smear findings?

Back 82

1. beta26 glu --> lys
2. Southeast Asia
3. CBC shows thalessmic indices
4. numerous target cells

Front 83

HbD & G
1. clinical presentation?
2. gel findings on cellulose vs. citrate?
3. how to distinguish the 2?

Back 83

1. clinically normal
2. cellulose acetate = band runs with HbS, citrate = band runs with A
3. HbG is an alpha chain defect thus may produce 2 HbA2 bands.
HbD is a beta chain defect

Front 84

Hb Lepore
1. geographic prevalence?
2. What Hgb findings should raise suspicion for this?
3. gene abnormality?
4. location on gel electrophoresis?
5. T/F HbF is low

Back 84

1. Mediterranean, especially Italy
2. whenever less than 30% (usually 15%) HbS present
3. Fusion between delta and beta genes
4. runs with HbS on cellulose (only 8-15% of total Hb)
5. False may be as high as 20%

Front 85

Hb Constant Springs (Hb CS)
1. T/F doesn't affect Hgb indices
2. mutation?
3. what hemoglobins are produced in heterozygous adults and newborns?

Back 85

1. False, causes thalassemic indices
2. mutation in alpha gene stop codon, producing abnormally and inefficient long transcript that produces thalassemia
3. Adults = HbA, HbCS, HbA2, and alphaCS-delta (4 band bands on cellulose gel)
Newborns = HbF and alphaCS-gamma also seen in addition to above

Front 86

High oxygen affinity hemoglobins
1. characteristic O2 dissociation curve finding?
2. Findings on Hgb studies?

Back 86

1. left shift (diagnostic)
2. Can't be resolved on gel or HPLC, key is erythrocytosis on CBC

Front 87

Unstable hemoglobins
1. characteristic peripheral smear findings?
2. what physical state may precipitate hemolytic crisis?
3. How is screening for them carried out?
4. Examples?

Back 87

1. Heinz bodies and bite cells
2. oxidative stress
3. incubating lysedred cells with 17% isopropanol, causes precipitation of unstable hemoglobins
4. Hbs Hasharon, Koln & Zurich only Hb Hammersmith associated with severe hemolysis

Front 88

Methemoglobin (Hi)
1. how is different from normal hemoglobin?
2. what causes these changes?
3. T/F Hi is capable of combining with oxygen

Back 88

1. The iron in the Hb molecule is in the oxidzied ferric (Fe+++) state instead the usual ferrous (Fe++) form
2. often due to oxidation of hemoglobin
3. False, Hi is unable to combine with oxygen

Front 89

1. T/F methemogobin (Hi) is normally present in the body
2. How is Hi normally metabolized/

Back 89

1. True, normally a small degree of Hb oxidation, up to 1.5% of Hb is Hi
2. reduced in erythrocytes by NADH-dependent methemoglobin reductase system

Front 90

1. What's the threshold of methemoglobin (Hi) before causing cyanosis?
2. Gross appearance of blood?

Back 90

1. When Hi reaches 10% of total Hb (around 1.5 g/dL) cyanoss results
2. Chocolate brown color

Front 91

Which of the following is capable of detecting methemoglobin?
A. co-oximeter
B. pulse oximeter
C. arterial blood gas analyzer

Back 91

A. CORRECT
B&C. INCORRECT, both estimate oxygen level by emitting red light (wavelength 660 nm) absorbed by oxyhemoglobin and infrared light (940 nm). Methemoglobin absorbs both of these wavelengths so it isn't detected

Front 92

What causes hereditary methemoglobinemia?

Back 92

Either deficiency in the reductase system or abnormal hemoglobins (HbM) upon which this enzyme cannot act

Front 93

What is HbM?

Back 93

A group of abnormal hemoglobins that prefer the ferric (methemoglobin) state due to various amino acid substitutions

Front 94

At what age is hereditary methemoglobinemia clinically apparent?

Back 94

Cyanosis appears at 6 months of age, unless there's M fetal Hb. If so cyanosis abates at about 6 months

Front 95

Where are most M hemoglobins found on routine gels?

Back 95

they run with A

Front 96

Common causes of acquired methemoglobinemia?

Back 96

Exposure to drugs or chemicals that increase the formation of Hi, common examples include: nitrites, quinones, phenacetin, and sulfonamides

Front 97

Why are nitrites part of the treatment for cyanide toxicity?

Back 97

They produce methemoglobin which has a high affinity for cyanide and chelates it

Front 98

What's the treatment for methemoglobinemia?

Back 98

Methylene blue, which reduces Hi to Hb

Front 99

Sulfhemoglobin (SHb)
1. How is it formed?
2. What are Heinz bodies?
3. T/F SHb can't transport oxygen

Back 99

1. when Hb is oxidized in the presence of sulfur
2. precipitate of SHb when it's further oxidized
3. True

Front 100

T/F Unlike Hi, SHb can't be reduced to Hb

Back 100

True

Front 101

At what level is SHb normally present and at what level does it cause cyanosis?

Back 101

Normally present at >1% of total Hb, cyanosis manifests at around 3-4% or 0.5 g/dL

Front 102

What conditions may increase sulfhemoglobin?

Back 102

Presence of sulfonamides and C perfringens bacteremia (eneterogenous cyanosis)