Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMT-dos > G6PD anemia/hemochromatosis > Flashcards

G6PD anemia/hemochromatosis Flashcards

1
Q

G6PD Deficiency Anemia

general

A

Enzyme protects RBCs from oxidative stress
Most patients do not have hemolysis unless challenged with oxidant stress
Episodic
Hemolysis results from exposure to fava beans, infections, or drugs
Normally, the activity of G6PD falls exponentially as RBCs age, with half-life of 62 days
The half-life is much shorter in the G6PD variants associated with hemolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

G6PD deficiency (glucose 6-phosphate dehydrogenase)

epidemiology

A

X-linked recessive disorder
More prevalent in Africa, Southern Europe, Middle East, Southeast Asia
G6PD A- variant: 10-15% African American males (rarely homozygous female)
Similar frequencies in Western and Central Africa
Primaquine sensitivity
Worldwide, geographic prevalence correlates with distribution of malaria
Most with G6PD deficiency are asymptomatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

GPD6 anemia

Clin Man

A
  • Jaundice
  • During hemolysis:
    Moderate to severe normocytic anemia
    “Bite cells”
    Heinz bodies
    As hgb breaks down, forms Heinz bodies that damage RBC membrane leading to premature removal
    Acute renal failure
  • G6PD Assay ↓
    May be falsely increased during hemolysis

In most cases no specific treatment
Avoid exposure to triggers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

GPD6 anemia

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

GPD6 anemia

Oxidative medications to avoid

A

Dapsone
Methylene blue
Phenazopyridine
Primathoprim/sulfamethoxazole
Sulfadiazine
Pegloticase
Quinolones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

G6PD Deficiency

Tx

A

Acute hemolytic episode
Remove/treat inciting agent
Hydration
Possible transfusion with severe anemia
Prevention is key!

**If patient at risk, previously asymptomatic, develops hemolytic anemia due to infection or medication, suspect G6PD Deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Paroxysmal Nocturnal HemoglobinurIa (PNH)

general, prognosis, Dx

A

Rare
Acquired stem cell mutation
Leads to
Increased complement activation
Hemolysis
Thrombosis
Prognosis: 10-15 years from diagnosis
Pancytopenia- affecting all cell line (RBC, WBC, Platelet)
Diagnosis: Flow cytometry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

PNH

Clin Man

A

Episodic hemoglobinuria
Reddish brown urine during night or early AM
Venous thrombosis in uncommon veins
Mesenteric
Hepatic
CNS
Painful skin nodules (thromboses)
Possible concurrent:
Myelodysplasia
Aplastic anemia
Risk for progression to Acute Myelogenous Leukemia (AML)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

PNH

Laboratory evaluation

A

Variable anemia- all 3 cell lines can be affected
Leukopenia +/-
Thrombocytopenia +/-
Reticulocytosis
Urine hemosiderin +
LDH ↑
Iron deficiency
Flow cytometry: PNH Clones
If aplastic anemia, may have < 2% present and NOT be PNH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

PNH

Tx

A

Mild disease
Requires no treatment
Severe hemolysis or thrombosis
Eculizumab (Soliris) infusions q2 weeks for life
Complement inhibitor
Reduces hemolysis, transfusion requirements, fatigue, and thrombosis risk
Increases risk of Neisseria meningitidis infections
Meningococcal vaccine
Severe disease
Allogenic stem cell transplant may be curative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Eculizumab (Soliris)

MOA

A

MOA: Humanized monoclonal IgG antibody that binds to complement protein C5. Terminal complement-mediated intravascular hemolysis is a key clinical feature of paroxysmal nocturnal hemoglobinuria (PNH); blocking the formation of membrane attack complex (MAC) results in stabilization of hemoglobin and a reduction in the need for RBC transfusions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Eculizumab

Adverse effects

A

Adverse Effects (more common):
Infusion reactions
HTN
Headaches
Skin rash
Renal insufficiency
Fever

Pregnancy: crosses the placenta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Eculizumab (Soliris)

special warning

A

Special Warning:
Life threatening and fatal meningococcal infections may occur from using this medications
Requires meningococcal vaccination at least 2 weeks prior to the 1st dose
Reduces risk of infection
Consider antimicrobial prophylaxis
PCN or macrolide
Risk Evaluation and Mitigation Strategy (REMS) program (federal program)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Hereditary Hemochromatosis (HH)

general

A

Inherited disorder (autosomal recessive) in which increased intestinal iron absorption leads to an accumulation of iron to harmful levels
Skin, heart, liver, pancreas, pituitary gland, and joints
Caused by a HFE gene mutation on chromosome 6
Progressive disease recognized in 50’s to 60’s
Significant total-body iron accumulation takes years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

hemochromoatosis

Pathogenesis

A

Mutation of the HFE gene → dysregulation of hepcidin
Hepcidin
Master regulatory hormone of systemic iron homeostasis
Controlled by a feedback loop
Normally inversely related to serum iron
↑ iron, ↓ hepcidin

Effects ofgene mutation:
↑ Ironabsorption in the intestine: up to 2–4 mg of dietaryiron/day
↑ Iron deposition in different organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

hemochromomatosis

Clin man

early and late presentation

A

Manifestations depend on the degree ofiron accumulation
First symptoms usually develop between ages 40-60

Early symptoms are nonspecific
Fatigue
Feelings of weakness
Arthralgias - most often MCP and PIP joints of the 2nd and 3rd fingers

Later symptoms – iron overload
Abdominal pain
Hepatomegaly and hepatic dysfunction
Cardiomegaly
Weight loss
Bronze skin color
Erectile dysfunction
Diabetes mellitus

16
Q

hemochromomatosis

increased risk of infection of

A

Decreased host defenses:
Impairedphagocytosis and reduced lymphocyte proliferation
Increased risk of infection from siderophilic bacteria:
Listeria monocytogenes: foodborne transmission
Yersinia enterocolitica: foodborne transmission
Vibrio vulnificus: ingestion of uncooked seafood and wound infections after exposure of skin wounds to seawater

17
Q

hemochromomatosis

lab finding
Genetic testing

A

Diagnosis is often made in asymptomatic individuals through routine screening labs
↑ Serum ferritin
↑ % saturation/serum transferrin saturation (> 45%)
Abnormal liver function test
AST/ALT
Alkaline phosphatase
Genetic testing for HFE gene mutation
If a mutation is present, first-degree relatives of the patient should undergo genetic testing

18
Q

hemochromomatosis

additonal testing

A

MRI
Measure the degree of iron overload
Serum ferritin >1000 ng/mL
Hepatomegaly or clinical findings suggestive of liver disease
Abnormal liver function
Liver biopsy
Assess for the presence of iron and/or evidence of liver damage

19
Q

hemochromomatosis

increased risk of

A

HH-associated hepatic iron overload confers an increased risk of hepatocellular cancer (HCC)

20
Q

hemochromomaosis

tx

A

Careful intake of foods rich in iron (meat, raw shellfish)
Limit vitamin Csupplements (↑iron absorption)
No alcohol to limitliverinjury
No supplemental iron

Phlebotomy:
is the mainstay of treatment
1-2 units (250-500 milliliters)of blood taken once or twice a week
Total number of phlebotomies needed to remove the excess tissue iron depends on the degree of accumulated iron
Goal to obtain a serum ferritin level <50 ng/mL
Iron chelation
Used in certain cases of hemochromatosis with anemia
Liver transplant

21
Q

Aplastic Anemia

general

A

Bone marrow failure disorder resulting in pancytopenia (all cell lines affected)
Hypoplasia
Less mature cells produced
Leads to pancytopenia

Usually acquired mechanisms
Toxic
Radiation
Chemotherapy
Medications
Viral
EBV, Parvovirus, CMV
Autoimmune (autoreactive T cells)]Malignancy

22
Q

aplastic anemia

Clinical manifestations

A

Men > women.
Biphasic age distribution
Patients often look and feel remarkably well despite their counts
Symptoms of anemia
Bleeding (minor), easy bruising, petechiae
Infection (unusual first symptom)

23
Q

aplastic anemia

labs
Genetic studies

A

CBC with differential
Pancytopenia (most common)
Reticulocyte count ↓ (because bonemarrow is not functioning)
Serologic testing for infections

Bone marrow biopsy
Dilute aspirate
Core – mainly fat occupying the space
< 25% hematopoietic cells

Chromosomal studies
To help differentiate between with Myelodysplastic Syndrome (MDS) & PNH

24
Q

aplastic anemia

relapse and risk of disease progression

A

Relapse is frequent

Risk of transformation to Myelodysplastic Syndrome or leukemia

25
Q

aplastic anemia

severe disease criteria

A

ANC (Absolute Neutrophil Count) < 500mc/L
Platelet count < 20,000 mc/L
Reticulocyte < 1%

26
Q

aplastic anemia

curative therapy

A

Allogeneic hematopoietic stem cell transplantation
Younger patients (< 40) who fail immunosuppressive treatments

27
Q

aplastic anemia

Tx

A
  • Erythropoietic growth factors
    Epoetin or darbepoetin injections
  • Myeloid growth factors
    Filgastrim or Sargramostim
  • Blood product transfusions
  • Aggressively treat infections
    Severe neutropenia (ANC < 500)
    Can become life threatening quickly!
28
Q

aplastic disease

Severe disease
Tx

A

Triple immunosuppressive therapy (Medically fit patients) “EPAG”
Overall response was 94% at 6 months
-Eltrombopaq (Promacta)
-ATG (equine antithymocyte globulin; Atgam)
-Cyclosporine (Gengraf)

Lower intensity therapy (most patients)
ATG (equine antithymocyte globulin; Atgam) + cyclosporine
Overall response was 68% at 6 months
Requires hospitalization
Followed by cyclosporine maintenance for 6 months
1-3 months to see response (only will be partial)
Eltrombopaq (Promacta)

29
Q

Erythropoietic stimulating agents

A

Epoetin (Procrit) or darbepoetin (Aranesp) injections
MOA:
Induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells
Induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes.
Erythropoiesis-stimulating agents (ESAs) increase the risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access
Greatest risk with target Hgb >11gm/dL
Dosing: Weight/diagnosis based. Subq Inj once daily, weekly, monthly, etc
So, what is the goal?
Prevent transfusions

30
Q

Erythropoietic stimulating agents

adverse Rxns

A

Adverse Reactions (more common):
HTN
N/V
Fever
Thrombosis
A shortened overall survival and/or increased risk of tumor progression or recurrence has been reported in studies with breast, cervical, head and neck, lymphoid, and non-small cell lung cancer patients

Avoid in heart failure patients

31
Q

Granulocyte Colony Stimulating Factor (Myeloid growth factors)

Filgastrim (Neupogen) or sargramostim (Leukine)

(white bleed cell stimulators)

A

MOA: Granulocyte colony-stimulating factor (G-CSF) stimulates the production, maturation, and activation of neutrophils to increase both their migration and cytotoxicity
Dose: Varies by disease state; IV/SubQ up to once daily

Adverse Reactions
Chest pain
Splenic rupture *
Arthralgia
Fever

Pregnancy: Crosses the placenta

32
Q

antithymocyte globulin (Atg)

A

Equine antithymocyte globulin (Atgam)
MOA:
Immunosuppressant involved in the elimination of antigen-reactive T lymphocytes (killer cells) in peripheral blood or alteration in the function of T-lymphocytes
Induces complete or partial hematologic response in aplastic anemia
Dosing: weight/disease based
Pre-medicate with acetaminophen, diphenhydramine, and prednisone
Pregnancy: Crosses the placenta (progressively increases)

33
Q

ATG

Adverse reactions:

A

Anaphylaxis
Perform test dose
Serum sickness reaction (hypersensitivity reaction)
Fever, rash, polyarthritis or polyarthralgias
Chemical phlebitis with peripheral IV
Use central line
Worsening leukopenia/thrombocytopenia
Fever/chills
Headache
Rash
Arthralgia

34
Q

cyclosporine

MOA

A

Drug Class: Calcineurin Inhibitor (Immunosuppresant)

MOA: Inhibition of production and release of interleukin II and inhibits interleukin II-induced activation of resting T-lymphocytes
Different brands are not interchangeable
Dosing: Weight/dose dependent; PO/IV
Pregnancy: Crosses the placenta

CMT-dos (95 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions