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infectious disease > hemoglobinopathies > Flashcards

hemoglobinopathies Flashcards

1
Q

2 hemoglobinopathies

A
  • sickle cell
  • thalassemia
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2
Q

predominant adult hemoglobin

A

Hemoglobin A
* 2 alpha globin and 2 beta globin chains

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3
Q
  • Stiff, sickle-shaped red blood cells
  • Hemolytic anemia w/ significant clinical manifestations
A

Hemoglobin S: beta chain abnormalities

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4
Q
  • A lab test that separates
    DNA, RNA, or protein
    molecules based on their
    size and electrical charge
  • An electric current is used
    to move molecules
    through a gel with smaller
    particles moving faster
    than larger ones
A

Electrophoresis

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5
Q

caused by gene that results in HbS instead of HbA
* Abnormal beta-globin
* Autosomal recessive
* Causes shape distortion of deoxygenated Hgb

Common Chronic hemolytic anemia

A

sickle cell disease

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6
Q

how does sickle cell cause chronic organ damage

A

little ischemic events that cause lots of mini strokes and pain.

spleen usually first affected. cellular debris is cleaned out by spleen. it is working overtime and the gunk gets backed up in the spleen and it gets bigger and bigger. they’re spleen is not working.

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7
Q

how do sickled cells cause occlusive vascular crises

A
  • These cells are also more fragile—chronic hemolysis
  • Increased cell adhesion and platelet activation
  • Release of inflammatory molecules
  • Decreased nitric oxide availability
  • Viscous blood
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8
Q

Most common in individuals from or descended from Africa (90% in the US), India, the Middle East, the
Mediterranean, the Caribbean, and Central and South America

  • from malaria
A

sickle cell anemia

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9
Q

The betaS (sickle cell anemia) gene is seen frequently in

A

American Black children

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10
Q

when is sickle cell usually identified and symptomatic

A

identified on prenatal or newborn screening (everyone is screened)
Not symptomatic until 5-6 months of age.

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11
Q

how to confirm sickle cell after electrophoresis

A
  • Confirm the diagnosis with HbS electrophoresis or genetic testing to
    identify variant hemoglobins
  • May coexist with beta or alpha thalassemia, HbC
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12
Q

why is there a wide variation in clinical manifestations for sickle cell

A

hemoglobin F levels varies in people

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13
Q

What causes blood cells to sickle?

A

low oxygen problem

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14
Q

What is the role of hemoglobin F?

A

Transporting oxygen from mothers bloodstream to the developing fetus during pregnancy

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15
Q

Why are these patients immunocompromised? (Sickle cell)

A

Damaged spleen which works to filter out bacteria and other pathogens

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16
Q

signs and symptoms of sickle cell disease

A
  • Chronic hemolytic anemia
  • Jaundice
  • Calcium bilirubinate gallstones
  • Splenomegaly in childhood
  • Poorly healing skin ulcers over the lower tibia
  • Bone necrosis
  • Can lead to osteomyelitis** (SICKLE CELL VIGNETTE)
  • Salmonella, Staph
  • Risk for life threatening anemia
  • Hemolytic or aplastic crises (usu after infection)
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17
Q

sickle cell lab findings

A
  • Chronic hemolytic anemia
  • Hct is usually 20–30%.
  • Peripheral smear: 5-50% of RBCs are sickled
  • Reticulocytosis: 10–25%
  • Nucleated RBCs
  • Hallmarks of hyposplenism: Howell-Jolly bodies and target cells
  • asplenia
  • WBC count is often elevated to 12,000–15,000/mcL (12–15 × 109/L)
  • Reactive thrombocytosis may occur
  • Elevated indirect bilirubin
  • Confirm diagnosis with electrophoresis: HbS
  • Subset of Pts have persistent HgbF
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18
Q

abnormal red blood cells with nuclear remnants/clusters of DNA

  • spleen is not working because these are usually removed from the body
A

Howell Jolly bodies

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19
Q

RBCs w/central round Hgb and pale rim

A

target cells

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20
Q

hallmark of sickle cell lab findings

A

Howell jolly bodies

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21
Q
  • Moderately severe hemolytic anemia
  • Reticulocytosis, hyperbilirubinemia
  • Permanently sickled cells
  • Chronic sickle cell
  • Tissue hypoxia with damage
  • Spleen, heart, kidneys, lungs
  • Renal damage
  • Growth impairment
  • Risk for infection d/t spleen impairment (by adulthood asplenia)-
    encapsulated organisms
  • Pneumococcus pneumoniae, Haemophilus influenza
  • Septicemia, meningitis
A

CHRONIC sickle cell disease

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22
Q
  • Vaso-occlusive crises, also called pain crises ***
  • Vicious cycle of sickling, obstruction, hypoxia –> sickling….
  • Hgb release from sickled cells binds and inactivates NO
  • Episode of hypoxic injury and infarction
  • Most patients with SCA experience pain by the age of 6
    years.
  • Can be triggered by infection, dehydration, hypoxemia, cold
    temperature, low humidity, stress, acidosis
  • Most of the time no specific trigger is known
  • Bones, lungs, liver, brain, spleen, penis
  • Bones are most common site in children—distinguish from osteomyelitis
  • Hand-foot syndrome, ie dactylitis**

Perform a thorough evaluation for other life-threatening causes that can be misattributed to sickle cell pain

A

ACUTE CRISIS sickle sell disease

23
Q

complications of sickle cell disease: acute crisis

A
  • Vaso-occlusive crises
  • Not associated with acute hemolysis
  • Acute chest syndrome-can be fatal
  • Crisis of the lungs
  • Fever, cough, chest pain, pulmonary infiltrates
  • Pulmonary inflammation can cause sluggish blood flow
  • What then?
  • Priapism
  • 45% of males after puberty, can lead to ED
  • Stroke, retinopathy
24
Q

Sequestration crises-can be fatal

A
  • In children with intact spleens
  • Entrapment of RBCs leads to rapid spleen enlargement
  • Hypovolemia –> shock
25
Q

Aplastic crises (bone marrow stops working)

A
  • Infection of red cell progenitors with parvovirus B19
  • EPO cessation and sudden worsening of anemia
26
Q

SCD treatment

A

allogeneic hematopoietic stem cell transplantation
(if performed before the onset of significant end-organ damage (for kids))

Hydroxyurea
(reduces complications, can be started at 9 months, increases Hgb F
* Used for more than 3 or more pain crises a year)

  • Abx (helps in infection)
27
Q

prophylactic Abx for kids with sickle cell

A
  • Prophylactic PCN 125 mg orally twice daily until age 3 years
  • Then 250 mg orally twice daily until age 5 years
  • longer if pneumococcal vaccination series has not been completed or if there
    is history of invasive pneumococcal infection or splenectomy
  • Routine vaccinations plus the following:
  • 23-valent pneumococcal polysaccharide vaccine (in addition to 13-valent
    conjugate pneumococcal vaccine) by age 5 years
  • Haemophilus influenzae type b for unvaccinated children > 5 years old
  • Meningococcal vaccines: quadrivalent in infancy and Meningococcal B vaccine
    at age 10 years
  • Additional screenings (Proteinuria, HTN, retinopathy and others)
28
Q

SCD Crisis management

A
  • Oxygen for sats <95%
  • Fluids
  • Pain control
  • Fever control if needed
  • Transfusion if needed
  • Incentive spirometry
  • Abx-for acute chest syndrome
  • Monitor for and treat renal failure
  • LMWH tinzaparin-shortens course
  • Adjuvant therapy includes hydroxyurea, antihistamines, anxiolytics, and antiemetics
  • Splenic crisis-monitor for hypovolemic shock
  • Aplastic crises-supportive care and transfusions as needed
29
Q
  • Adaptive mutation
  • Pts many not know they have it
  • Amount of hemoglobin S varies
A

sickle cell trait

30
Q

How does sickle cell trait manifest?

A

we don’t really know

31
Q
  • Pulmonary embolism?
  • The renal medulla is acidotic
  • Causes sickling
  • Microscopic or gross hematuria
  • Hyposthenuria
  • Possible CKD-this relationship is not clear
  • 2010 NCAA mandated screening for all Division 1 Athletes
  • More likely to die from sudden death from high exertion
  • Often on the first day of training
A

sickle cell trait

32
Q

what to recommend to athletes with SCT

A
  • stay hydrated
  • set your own pace
  • avoid altitude
  • don’t exercise if you don’t feel well
33
Q
  • Reduced synthesis of alpha or beta globin chains
  • Hereditary—autosomal recessive
  • RBCs don’t get sufficient hemoglobin—>anemia
  • Small, pale RBCs
  • Normal or elevated RBC count
  • Usu w/ elevated Retic count
  • Significant variability in clinical presentation
A

thalassemias

34
Q

Two alpha-globin gene copies on each chromosome 16
* i.e. four genes
* usually d/t gene deletion**
* More affected alleles = more severe
* 5% of world’s population

A

alpha thalassemia

35
Q
  • One beta-globin gene copy on each chromosome 11
  • usually a point mutation***
  • 1.5% of world’s population
A

beta thalassemia

36
Q

Hemolytic anemia of variable severity: Worse with infections or other stressors

  • Fatigue, dyspnea
  • Possible pallor, splenomegaly, hepatomegaly, jaundice
  • Frequent infections
  • Cholelithiasis

Mild-to-moderate thalassemia-like skeletal changes such as:
* maxillary hypertrophy
* skull “bossing”
* prominent malar eminences (bony abnormalities)

  • Leg ulcers (rare)
  • Delayed growth in children
  • Some level of iron overload–especially in older patients
A

alpha thalassemia signs and symptoms

37
Q

CBC:
- Microcytic, hypochromic anemia
- RBC count normal or increased
- Serum Fe an Fe stores normal or increased

Peripheral smear:
- Target cells: central round Hgb and pale rim
- Teardrop cells: formed by abnormal/fibrotic bone marrow
- basophilic stippling: basophilic granules that are dispersed through
the cytoplasm of RBCs
- Heinz bodies in Hgb H – insoluble beta chain tetramers
- Howell-Jolly bodies - remnants of RBC nuclei that are normally removed by the spleen

  • Hemoglobin electrophoresis
  • Genetic testing
A

alpha thalassemia labs

38
Q

hallmark of alpha thalassemia on labs

A

teardrop cells

39
Q

Carrier treatment

A

none

40
Q

trait treatment

A

none

41
Q

⍺-Thal. Minor treatment

A

folate, avoid oxidative stress (sulfa drugs), avoid supplemental iron

42
Q

Severe disease (Hb H) treatment

A
  • Blood transfusions weekly
  • Iron chelation therapy
  • Splenectomy (stops RBC destruction)
  • Bone marrow transplant (Hgb H)
43
Q

Hb bart’s treatment

A

incompatible with life

44
Q

Reduced or absent beta chain synthesis
* Increase in ratio of HgbA2 (delta) and Hgb F (gamma) relative to HgbA
* A variety of molecular defects
* Beta0=absent
* Beta+=reduced
* Variable degree

A

beta thalassemia

45
Q

Minor beta thalassmia clinical presentation

A

asymptomatic. May have mild anemia

46
Q

Intermedia beta thalassemia clinical presentation

A

Anemia, hepatosplenomegaly, bony disease

47
Q

Major (Cooley’s Anemia) beta thalassemia clinical presentation:

A
  • Asymptomatic at birth due to fetal Hgb
  • Symptomatic at 6 months as fetal Hgb declines
  • Frontal bossing and maxillary hyperplasia due to extramedullary hematopoiesis
  • Hepatosplenomegaly
  • Severe anemia with jaundice, dyspnea, and pallor
  • Osteopenia (pathologic fractures)
  • Iron overload
  • Pigmented gallstones
48
Q

CBC:
* MCV low
* RBC count may be increased
* Serum iron may be increased

  • Peripheral smear:
  • Target cells
  • Teardrop cells
  • Basophilic stippling
  • Nucleated RBC’s
A

beta thalassemia labs

49
Q

what does electrophoresis for beta thalassemia trait show

A

Increase in Hgb A2 –> alpha chains
couple with delta chains

50
Q

what does electrophoresis for beta thalassemia major show

A
  • Little to no normal Hgb A
  • Increase in Hgb F –> Alpha chains
    couple with gamma chains
51
Q

Beta Thalassemia Diagnosis: X-rays

A

Bossing of the skull with “hair on
end” appearance (HALLMARK)

Result of extramedullary
hematopoiesis that results in new
bone formation in the skull producing perpendicular radiations

52
Q

beta thalassemia treatment

A

No care necessary. Genetic counseling may benefit

53
Q

beta thalassemia Major/severe anemia treatment

A
  • Periodic blood transfusions
  • Vitamin C and folate supplementation
  • Avoid excess iron
  • May require iron chelation w/ Deferoxamine
  • Splenectomy if refractory
  • Bone marrow transplant

infectious disease (13 decks)

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