Anaemia/iron/haemochromatosis Flashcards
When do you look for iron deficiency
Microcytic anaemia
Symptoms of
At risk of/prev IDA- heavy menstrual, veggie
Pre surgery - avoid transfusion
Standard pregnancy management - booking and 28 weeks
Iron deficiency symtpoms
Anaemia
Fatigue, poor conc, low mood
Hair thinning
Itch
Restless legs
Koilonychia, glossitis, pica
causes IDA
Diet - veggie
blood loss
malabsorption
Increased requirement for iron eg pregnancy
Blood loss causing IDA
Menstrual
GI bleed - ulcers, malignancy, inflammation, parasites
Blood donation
Who qualifies for an endoscopy/colonsocopy from IDA
All men and post menopausal women considered unless clearly non GI bleed
Investigation of IDA
Colonsocopy, endoscopy
Malabsorption - coeliac screen, helicobacter pylori
Urinalysis
Blood tests
What see on FBC in IDA
Hb - low or nomal
MCV<80 (some may be normal)
MCH <27
RBC - low/normal, RDW - normal/high
Blood film IDA
Hypochromia, microcytosis, pencil cells
Why does a normal or high ferritin not necessarily exclude IDA
High with inflammation and liver disease
What ferritin evels suggest IDA
<15 = no stores - pathogonomic
<30 - IDA
30-50 borderline/probable
<100 - = inflammation = possible IDA
Iron studies
Serum iron
Total binding iron capacity
Transferrin saturaiton
Not very useful IRL
Secondary tests for iron deficiency
Iron studies
Reticulocyte Hb <28
% hypochromic cells >6%
Zinc protoporphyrin >80
Oral trial of iron - improves by 20g/L in 3 weeks/Hb increases
Low MCV causes
IDA
Thalassemia/Hbinopathy
Anaemia of chronic disease
Lead poisonning
Inherited sideroblastic anaemia
Treating IDA
Diet
100-200mg elemental iron per day, 3 months after normal Hb
Aim for ferritin >50
What dietary iron is best absorbed
Haem iron from meat or fish
How is iron absorbed better
Prior to food - acid stomach
With vit C - fresh orange juice
Avoid antacids and tannins
What to do if oral iron not tolerated
Reduce dose to alternate days
Lower elemental iron/change formulation
Take w vit C, with food
Treat inflam conditions
Laxatives if constipated
Ensure compliance and no malabsorption, no haematinic deficiency
How does parenteral difffer to oral iron in terms of Hb
May initially work faster
4-6 weeks similar levels of Hb to oral iron
When is parenteral iron useful
Inflammation
Dialysis
Not tolerated oral despite trying
High levels of blood loss eg HereditaryHT elagniectasia
Complications pareneteral iron
Rare anyphylaxis, Low PO4, extravasation
What is hyperferritinaemia
Ferritin levels are high, doesnt necessarily mean iron is high
Causes of hyperferritinaemia
Inflammation incl AI disease, infection, malignancy
Liver disease, metabolic syndrome
Genetic haemohc=chromatosis
Renal failure
Myedodysplasia
THalassemia intermedia/major + other rare anaemias
Chronic blood transfusion
Porpphyria cutanea tarda
Other rare syndromes eg hereditary hyperferritenemia cataract syndrome, gauchers, acaeruloplasminaemia, friedrichs ataxia
What is high ferritin in men vs women
> 300 men
200 women
What do next when raised ferritin
Check FBC, U+Es, LFs, inflam markers, transferrin saturation
What does a high ferritin and abnormal FBC warrant investigatio for
Iron loaing apaemia
Haemolysis
Myedoplasia Thalassemia
When test for genetic haemochromatosis when high ferritin?
When trasnferrin saturations also high
eg >50% in men >40% in women
Check HFE genotyping
What can causes an isolated high ferritin
inflammation, malignancy, liver disease, metabolic syndrome etc
Genetic haemochromatosis why often not diagnosed
Often no clinically significnat iron overloading
Iron overlaoding symtpoms in haemochromatosis
Joint damage, osteoporosis
Endocrine - diabetes, gonadal sailure
Bronzed skin
Liver failure/cirrhosis HCC
Cardiac iron loading
Does high ferritin always cause iron overloading symptoms
No - only in people who have genetic haemochromatosis
Managment of haemochromatoss
Venesection 3-4 x a year aim for ferritin <50ug/L
Check for complications, family
Iron chelation if cant do venesection
Avoid vit C, reduce alcohol
Four initial tests for anaemia
Hb
MCV
Reticulocyte count
#Blood film/smear
If MCV <80 what differnetial anaemias suspect
IDA
Thalassemia
Anaemia of chronic disease
Lead poisonning
Sideroblastic
What does a normal MCV and low reticulocyte count suggest differentials
Bone marrow failure
BM infiltration
Organ failure/endocrinopathy
What does a normal MCV and high reticulocyte count suggest differentials
Bleeding
Haemolysis
Treated nutritionaldeficinecy
What differentials when MCV >100 eg macrocyticc
B12/folate deficinecy
Liver disease
Alcohol
Drugs - methotraxtae, sulfasalazine, ART
thryoid disease
What reticulocyte level would you expect in an anaemic patient with a healthy bone marrow response?
High - increased erythropoiesus
What are reticulocytes
Immature RBCs
Clinical features of haemolytic anaemias
Pallor
Jaundice
Gallstones pigmenet
Splnomegaly, may have hepatomegaly
3 lab features common to all haemolytic anaemias
Reticulocytosis
Elevated LDH
Eleated indirect - conjugated - bilirubin
What ceclls see in warm AI haemolytic anaemia (WAIHA)
Spherocytes
What morpholoy see in cold AIHA
Agglutination
What cells see in microangiopathic haemolytic anaemia -MAHA
Shistocytes, some spherocytes
What cells see in oxidative haemolyiss
Bite cells
What does intravascular haemolysis occur in
ABO incompatability
G6PD defiency
PNH - Paroxysmal nocturnal hemoglobinuria (complement destorys RBC)
PCH - AI after cold exposure, also complement
Clostridial sepsis (c.difficile)
Mechanical valve
Severe burns
Characteristics of IV haemolysis
- plasma free haemoglobin (hemoglobinemia)
- decreased haptoglobin (bound by free Hb)
- increased methaemoglobin (heme with Fe3+)
- haemoglobinuria and hemosiderinuria
- chronically, may lead to iron deficiency
What conditions see extravascular haemolysis in
RES, most causes of haemolytic anaemia
Intrinsic RBC anaemia - congenital - where effected in cell by what disease
1) membrane – hereditary spherocytosis, elliptocytosis
2) haemoglobin – sickle cell disease, thalassaemia’s
3) enzymes – G6PD, PK deficiency
Secondary causes of WAIHA
Lymphoma
Drugs
Connective tissue disease
Causes IgG AB to antigen on RBC
Treating WAIHA
Primarily extravascular haemolysis
- Treatment: steroids, treat underlying cause
- Azathioprine, cyclophosphamide, etc for steroid-sparing
Secondary causes Cold AIHA
lymphoma (adults), infections (children; EBV, Mycoplasma pneumoniae)
Antibodies CAIHA vs WAIHA
cold = IgM, antibody target I or i
warm = IgG, many targets incl Rh
How does CAIHA work
- Primarily intravascular haemolysis; degree of haemolysis determined by thermal amplitude of cold agglutinin
Treatment CAIHA
NOT STEROIDS - dont work
Supportive in children
underlying cause adults
Cyclophosphamide
TRANSFUSE through blood warmer
Paroxysmal cold haemoglobinuria summary
– IgG Ab against p (globoside) antigen, binds RBC at 4C, activates complement when re-warmed to 37C: associated with viral infections, syphilis.
Alloimmune anaemias
haemolytic transfusion reactions (acute and delayed),
haemolytic disease of the new born.
Summary of PNH
– acquired defect in PIG-A gene, unable to anchor proteins that require PIP, complement-mediated
chronic intravascular haemolysis marked by acute attacks
Drug induced haemolysis causing drugs
Drug absorption (penicillin)
ii. Membrane modification (cephalosporin)
iii. Immune complex (quinine)
iv. Autoantibody – levodopa, methyldopa
Non immune mediated anaemias
RBC fragmentation syndrome
Infection
Toxins
Chemical agents eg copper, arsenic, hypophosphatemia
Burns, downing, march heamoglobinuria
RBC fragmentation syndromes
Cardiac (valves, bypass, AVMs)
ii. MAHA – TTP/HUS, malignant HTN, DIC, HELPP, pre-eclampsia
When do you suspect Beta thalassemia in Hb electrophoresis
Hb A2<3.5%
Electrophoresis and microcytic anaemia
- Suspect β thalassaemia when Hb A2 >3.5%
Normal Hb electrophoresis does not exclude α thalassaemia or iron deficiency
In concomitant iron deficiency, Hb electrophoresis may be falsely normal; therefore, it should be repeated once iron stores are replete
If α-thalassaemia suspected, order DNA testing
What rule out in microytic anaemia
GI investigations, rule out intravascular haemolysis, celiac disease, H .pylori, congenital
When expect Hb to respond to iron in IDA
4-6 weeks
If doenst further investigations
What decereases iron absorption
Inhibited by calcium, tea, coffee, phytic acid (grains, legumes) and
decreased gastric acidity (proton pump PPI)
Side effects of iron
nausea, vomiting, dyspepsia, constipation, diarrhoea, dark stools; generally dose-related and usually subside with continued therapy (except dark stools)
Oral preps of iron
Fumarate 210mg = 65 mg elemental iron
Gluconate 300mg = 35 mg elemental iron
Sulphate 200mg = 65 mg elemental iron
Feredetate 190 mg/5ml = 27.5 mg/5ml elemental iron
Maltol 30mg = 30 mg elemental iron
What is HHT
Hereditary hemorrhagic telangiectasia, also known as Osler–Weber–Rendu disease and Osler–Weber–Rendu syndrome, is a rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain.
cause bleeding, known as arteriovenous malformations (AVMs).
Normal HbA1c
Men - 130g/L
Women - 115g/L
Varies with age
Lifespan of RBC
3 weeks for erythropoeisis
3 month life cycle in circulation
What stimulates erythropoietin release
Decreased oxygen
Causes of deveased RBC production
Reduced EPO response - kidney or chronic inflammation
Raw material deficiencies eg chronic inflam - less use iron
Reduced bone marrow production - infiltration (cancer, infection), aplastic anaemia, myelosupression (drug, infection)
INfections and drugs causing myelosupression
Chloramphenicol, alcohol
Chemo
DMARDs
Propothyouracil, carbimaxole
Tacrolimus
Hydroxyurea
Parvovirus
Causes increased RBC destruction
Haemolytic anaemias - AI, drug induced, hered spherocytosis
Haemoglobinopathies
Hypersplenism - RBCs out of circulation eg portal hypertenion
What can low folate indicate
Increased demand for RBC eg pregnancy, lactating
investigations in microcytic anaemia
Ferritin/iron studies
Further depends on symptoms
Consider haemoglobinopathy screen
investigations for normocytic anaemia
Blood film, reticulocytes (low - bone marrow)
U+Es, LFTs
CRP
Ferritin/B12/folate
HIV
Macrocytic anaemia investiations
Blood film
Reticulocutes
B12/folate
LFTs, U+Es
LDH, haptoglobin
DAT - haemolysis
Consider myeloma screen - serum Igs and serum free light chains
HIV
Anaemia of chronic disease why and treatment
Inadequate usage of stored iron
Inadequate eryhtropoietin response to anaemia
RBC life span
Treat - underlying cause, IV iron, EPO injections
Hypersegmented neutrophils ass with
Haemotinic deficiencies
Pernicious anaemia markers
Low B12
Intrinsic factor
Parietal cell antibodies
Why need to do endoscopy in B12 deficiency anaemia
Ass w gastric cancer
