liveonearth (liveonearth) wrote,
liveonearth
liveonearth

Hemochromatosis

When ordering therapeutic phlebotomy you'll be asked to specify volume drawn (500mL is the default), weekly/biweekly/monthly draws, for a 12 month period. After 12 months a new prescription is required. According to an org specializing in blood iron disorders, the hemoglobin cutoff below which you should not draw is 12.5. The normal HGB range is 12-16 ish.

INCIDENCE of Hereditary Hemochromatosis (HHC)
1 of the most prevalent genetic conditions in the world
affects 1:300 persons of Northern European decent
autosomal recessive

GENOTYPE
Three mutations of the hemochromatosis gene (HFE)
C282Y, H63D (histadine to aspartic acid) and S65C
Other mutations may affect persons of African and Mediterranean decent, not yet identified
affects pts typically homozygotes for C282Y and compound heterozygotes
-->inappropriately increased absorption of dietary Fe
phenotypic expression variable, mb influenced by iron intake and/or blood loss

PATHOPHYSIOLOGY
primary: incr intestinal absorption of Fe-->max out storage methods & ROS generated by metabolism-->Fe3+ overwhelms body's ability to carry out Fenton Rxn, free radicals and oxidative stress-->cell damage-->cell death via apoptosis
secondary: usudt excessive blood transfusions (iatrogenic), mbdt thalassemias (can't utilize Fe)

S/SX
none or unexpected: most are ASX
mc sx: weakness, fatigue,
decr libido
skin pigmentary melanin abnormalities (gray) ("bronze diabetes")
arthralgia/arthritis
movement disorders
psychosis
deafness
diabetes mellitus
rashes?

COMPLICATIONS
Fe deposits in liver, heart, testicles
-->dm, hypogonadism, CVD (cardiomyopathies), liver cirrhosis, osteopenia/porosis
64% of men with this dz have osteopenia
osteoporosis, osteopenia overall with incr Fe: 25% and 41% respectively
a cause of MS?

SCREENING
is indicated, find lots of women who are iron deficient
start screening men in their 30's, repeat in 40's
do iron study, tibc and ferritin and all
transferrin sat over 45-50, ferritin over 300: that's positive-->get genetic testing

DIAGNOSIS
most sensitive test is serum transferrin saturation
transferrin saturation = (serum Fe/TIBC) x 100. (normal is 20-50%)
>45% is ~98% sensitive
low rate of false positives
in most men with HHC, TS exceeds 55%; women, 50%

IF TS elevated and ferritin > 300 run HFE genotype
if positive, run genotype on all first degree relatives (and spouse if children)
children don’t need to be checked until adolescence
genetic test $120 LabCorps

serum ferritin is a good test for determining either high or low body iron stores
but is an acute phase reactant-->subject to misinterpretation
in cases of liver dz (necrotic hepatocytes release ferritin), infx, ca, inflammatory illness

IF LFTs abn-->BX mb necessary to assess liver fibrosis

IF serum ferritin < 1000mcg/L, AST is normal, and NO hepatomegaly
-->risk of fibrosis is minimal

TREATMENT: PHLEBOTOMY
remove excess iron as quickly as possible and treat complications
therapeutic phlebotomy - remove 1 or 2 units of blood/week
until hemoglobin < 13 in men; 11 in women
then check serum ferritin
goal: reduce ferritin to ~50mcg/L
each 500ml of blood contains 200-250mg iron
1 mcg/L of serum ferritin = ~ 7-8mg of stored iron
removal of 1 unit of blood-->should reduce ferritin by ~ 30mcg/L
timeframe: 3-24 mo to reduce iron levels to normal

pts used to have to pay for phlebotomies
now American Red Cross is providing phlebotomies at no charge and using this blood
in Portland call ARC Special Collections at (503) 280-1443 to get the required paperwork

maintenance is ~ 2-4 phlebotomies /year
keep ferritin between 20 and 80 mcg/L

TREATMENT: DIET AND LIFESTYLE
not sufficient as a sole treatment modality
could decrease the number of maintenance phlebotomies required
--avoid supplemental iron
--avoid red meat and liver, consider vegetarian diet
--avoid EtOH (may incr iron absorption, challenge liver)
--avoid excess vitamin C or don't take with foods containing Fe (may incr Fe absorp)
--drink black tea or coffee with iron-containing foods to decrease intestinal absorption of Fe

IRON
most common deficiency in US and world
essential in many proteins and enzymes: hemo/myo globin, cytochromes (ATP production)
carried in blood bound to transferrin
in myoglobin, resp enzymes, hemoglobin, marrow
storage in reticuloendothelial system: liver, spleen, marrow
also in ferritin, hemosiderin
ferritin is most useful measure clinically
two oxidation states: ferrous +2 or ferric +3
useful in redox rxns as cofactor
in catalase and peroxidase (anti-oxidant enzymes)

IRON ABSORPTION
varies from 3-35% depending on many factors
heme iron is 10-15% of iron in mixed diets but 1/3 of total absorbed iron
non-heme iron in animal and plant foods, fortified foods and supplements
absorbed in +2 ferrous state in intestine, best for passage through membrane
+3 ferric state binds to transferrin, ferritin
vitamin C helps absorption of iron by keeping it in +2 state
seen on supplements: ferrous gluconate (gentle), ferrous sulfate, "reduced" iron
increased by: def, growth, preg,
food factors: heme, vit c, animal flesh proteins beneficial because they contain heme group which we absorb heme very well (3-4x better than non-heme iron)
decreased by: hypochlorhydria and other GI pathologies, oxalate (spinach), phytate (in bran), tannate (in black tea), other divalent cations (Ca++)

ABSORPTION BLOCKED BY
phytate in legums and whole grains
oxalate in spinach
polyphenols in fruit, veggies, tea, coffee, wine

RANDOM STUFF FROM HERE DOWN, NEEDS SORTING

ANOTHER SOURCE FOR GENETIC TESTING: GENELEX
DNA test offered by Seattle-based Genelex Corp
to evaluate drug responses, paternity, or racial composition
find out if you have hemochromatosis, or celiac dz
http://www.healthanddna.com/
send a blood sample, results in 2 weeks
$600 gets you a genetic profile for drug processing, med dosing info and alternatives
some insurance companies will cover it
genemedrx is software measuring interactions and suggests alternative meds
send a sample from anywhere in world-->get report
physician gets passworded account and can review results with pt

FERRITIN
Normal Serum Ferritin: Males 40-340 ng/mL, Females 14-150 ng/mL
levels rise persistently in males and post-menopausal females
malignancy, liver disease and inflam dzs-->incr ferritin independent of iron stores
acute phase reactant prot (incr 1-2 days after onset of acute, peaks @ 3-5 days)
ferritin is the major iron-storage protein, primarily found in the liver
good indicator of available iron stores in the body in healthy person
1 ng/mL serum ferritin = about 8 mg of stored iron
severe protein depletion can decrease levels (take aa's to make other stuff, starvation?)

SERUM IRON LEVELS
a measurement of the iron bound to transferrin
normal: Males: 65-175 picograms/dL, Females: 50-170 picograms/dL
decr dt: stress, diet deficient, chronic blood loss, malabsorption, late preg, IDA, neoplasia
stress-->decrease by 65%, recovers to normal over the following week
incr dt: hemolysis, neoplasia, transfusions, high iron meal, supps, drugs, liver dz, lead tox
changes daily and is not a good reference for diagnosing anemia or hemochromatosis
IDA pts have normal serum iron 10-15 % of the time (ferritin better test)

TIBC
measure of transferrin in blood, free iron transport capacity
incr in: PCV
decr in: cirrhosis, hypoprot, hemolysis

ME PERSONALLY IN 3/09 at age 43
Iron 188 ug/dl (42-135 ref range)
% SAT (transferrin) 62% (20-50% ref)
TIBC is 303 ug/dl (218-385)

SOURCES:
Dr Nicolai's 2010 grand rounds presentation
the top of my head and my other journal entries
ancient biochem notes
Stecher's DI notes
Tags: blood, common conditions, hemochromatosis, iron, meat
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