Acquired Anaemia Flashcards
What are the general features of anaemia due to reduced O2 delivery
Asymptomatic if Hb falls slowly Fatigue Pallor - mucous membrane / creases SOB on exertion / rest Headache Chest pain Palpitations Dizzy due to hypoperfusion of brain Hair loss
If severe
Tachycardia
Systolic flow murmur
HF
What are features of anaemia due to underlying cause - ASK
Bleeding - menorrhagia / GI Sx / NSAID use
Malabsorption - diarrhoea / weight loss / poor diet
Jaundice if haemolysing
Splenomegaly
Lymphadenopathy
Fatigue
Weight loss / fever / night sweats
PMH anaemia / chronic disease / renal failure
What are the red cell indices
MCV - mean cell volume
MCH - mean cell Hb
What are the morphological description of cells
Hypochromic microcytic
Normochromic normocytic
Macrocytic
What are hypochromic microcytic
MCV low
MCH low
What are normochromic normocytci
Normal MCV / MCH
Just less cells
What are macrocytic
MCV high
What are the initial investigations of anaemia
FBC
Red cell indices
Blood film
U+E, LFT useful
What causes hypochromic
Iron deficiency Thalassaemia Secondary anaemia (30%) Lead poisoning Sideroblastic = very rare
What is the next step investigation for hypochromic anaemia
Serum ferritin
Ferritin low in iron deficiency
Ferritin high in sideroblastic / thalassaemia (TIBC low)
What causes normochromic normocytic
Acute blood loss - high ret
Haemolytic anaemia - high reitucocyte e.g. congenital
Normal or low reticulocyte Secodary anaemia Bone marrow hypoplasia - suspect if WCC / platelet down - Leukaemia / lymphoma / MM - Myelofibrosis / dysplasia / MGUS Aplastic anaemia
What causes macrocytis (not always anaemic)
Metagloblastic on film
Low B12 / folate -
Non-megaloblastic Alcohol Myelodysplasia Marrow infiltration Abnormal liver HYpothyroid Pregnancy
Non-megaloblastic - haemolytic (no issue with bone marrow) Drugs - Quinine - Hydroxychloroquine Congenital - Haemoglobinopathy - HS - G6PD Autoimmune Malaria Microangiopathy haemolytic anaemia - HUS - TTP - DIC
What is next strep for investigating macrocytic
B12/ folate assay
Bone marrow
What is most common cause of anaemia
Iron deficiency
Exam Q of normal Hb but microcytosis
If no risk of thalassaemia
Polycythaemia ruba vera
- Iron deficiency 2 to bleeding but increased red cells so Hb normal
What happens to absorbed iron
Absorbed in duodenum and jejunum
Stored in liver as ferritin
Transferred by transferrin in plasma
What is role of Hepcidin
Synthesied in liver in response to inflammation / renal failure / increased iron
Blocks ferroportin so reduced absorption of iron in inflammation / chronic disease
What can cause iron deficiency anaemia
Bleeding = most common in adults - GI CANCER / ulcer - Menorrhagia Poor diet = most common in children Malabsorption - Gastrectomy - Coeliac Increased requirement - Pregnancy / children
What are specific signs of deficiency
Classic anaemia Koilonychia Atrophic glossitis Angular stomatitis Post cricoid webs if Plummer Vinson Abdo and rectal exam
How do you investigate iron deficiency anaemia
Hx about causes
FBC +film
- Microcytic hypo chromic
- Target cell
Serum ferritin - low (beware as raised in inflammation etc)
Transferrin sats - low
TIBC - high
Endoscopy / coeliac serology or stool microscopy if travel Hx to rule out malignancy
2 week cancer if elderly with microcytic anaemia
What is important in HX
Weight loss Change in bowel Diet Medication - NSAID Menstrual PMH chronic disease
When can ferritin be high
Inflammation / CKD / malignancy / liver disease
Iron overload - haemochormatosis / transfusion
So do sats
How do you treat iron deficiency
Oral iron ‘ferrous sulphate’
Continue for 3 months once Hb back - want it to rise by 10 per week
IV iron if intolerant / or if cardiac signs e.g. SOB ON REST
Blood transfusion = very rare
Correct cause
Refer to GI
SE of iron
Nausea Abdo pain Constipation Diarrhoea Dark stool
How do you differentiate iron vs chronic disease
Iron
- TIBC high
- Ferritin low
AOCD
- TIBC low
- Ferritin high as inflammation
When is reticulocyte increased in normochromic
Acute blood loss
Haemolytic anaemia
When is reticulocyte normal or low
Secondary anaemia / chronic disease - CKD
Bone marrow infiltration
Aplastic anaemia
What can haemolytic be
Extravascular
- Warm
Intravascular
Both
What happens in intravascular
Red cells burst in circulation so tend to be much sicker
What are acquired extravascular causes
Auto-immune - can be
- Warm AB mediated
- Cold Ab mediated
Alloimmune
What drugs cause extra-vascular haemolytic
Methydopa
Penicillin
What are acquired intravascular causes
Non-immune Mechanical valve Severe infection / DIC Micro-angiopathic - PET / HUS / TTP / malignancy / drugs Malaria Paroxysmal haemoglobinruia
How do you Dx autoimmune
DAT - direct antiglobuin test +ve
What causes warm Ab
Idiopathic Auto-immune - SLE Drugs - methyldopa / penicillin CLL / lymphoma Rhd - IgG
What causes cold Ab - occur at cold temp
More commonly 2 to other diseases CHAD Infection - mycoplasma / EBV / CMV Lymhpoma Leukaemia SLE ABO - IgM
What causes allo-Ab
Transfusion reaction
Haemolytic disease new born
Where do warm Ab tend to occur
Extravascular
Where do cold Ab tend to occur
Intravascular
How do you Dx haemolytic / what are the symptoms
Symptoms - anaemia, jaundice - isolated hyperbilurbin, splenomegaly
History - FH, race, jaundice, drugs, travel Examination - jaundice, gall stones, HSM \+Ve DAT FBC - normocytic Reticulocyte - high Film - spherocytes Serum bilirubin - high High LDH Serum haptoglobin Malaria screened if hx of travel
What is serum haptoglobin
Low in intravascular
How do you manage haemolytic anaemia
Folic acid Correct cause Immunosuppression Steroid Ritixumiab Splenectomy to remove site Consider transfusion ITU as high clotting risk
How does chronic disease cause anaemia
Increased hepcidin which blocks absorption of iron
- Autoimmune
- Rheumatological
- Malignancy
- Chronic infection
What is aplastic anaemia characterised by and how is it Dx
Sudden failure of bone marrow (hypo plastic) Get aplastic crisis if no RBC produced Normochromic anaemia Low reticulocyte Pancytopenia - lymphocyte spare - Thrombocytopenia
Dx on bone marrow trephine or aspirate showing reduced cells
What causes
Parovirus = classic cause - Exacerpates sickle causing crisis Congenital ALL / AML Drugs - Anti-malaria - AED - carbamazepine - Cytotoxic - Chloramphenicol - Sulphonamide - Phenytoin - Anti-thyroid Infection - parovirus / hepatiis / HIV / EBV Radiation
What causes megaloblastic macrocytic anaemia
B12 / folate ONLY
Film = hypersegmented neutrophils
What causes non-megaloblastic
Myelodysplasia
Marrow infiltration
Cytotoxic drugs
What must you do if non-megaloblastic
Bone marrow
How does B12 / folate deificny present
Anaemia
Neuro-psychiatric - depression / psychosis
Neurological - paraesthesia / neuropathy
ALWAYS TEST FOR B12 DEFICINECY IF NEUROPATHY
SCAD
Neuro signs - involved in DNA synthesis
Take 1-2 years to develop symptoms as stores good
What causes B12 deficiency
Pernicious anaemia = main cause (autoimmune attack on intrinsic factor or gastric parietal cells)
Poor diet - alcohol / elderly
Increased demand - pregnancy
Gastric/ ideal disease
Malabsoprition - coeliac / tropical spure
Drugs - AED, methotrexate, trimethoprim
How is B12 absorbed
Binds to intrsinc factor secreted by gastric pariteal cells
Attaches to ileum and absorbed
What causes folate deficiency
Dietary
Increased requirement
GI pathology
How do you Dx B12 deficiency
Anti-intrinsic factor Ab = diagnostic and most important
Anti-patietal AB = specific
If present confirms pernicious
Film = hyperhsegmented neutrophils
How do you treat
Replace vitamin - B12 injection (can’t give oral if pernicious as can’t absorb)
Oral B12 if just deficiency e.g. poor diet
Oral folate
What must you do before treating folate
Ensure B12 normal as can worsen neuropathy / cause SCAD
How do you give B12
6 injections over 2 weeks
then 3 monthly
What are causes of macrocytosis
Alcohol Methotrexate / ARV / hydroxycarbamide Phenytoin due to altered folate metabolism Liver disease Pregnancy Hypothyroid Myelodysplasia
If patient presents to AMIA with acute low Hb what do you want to know
Is patient stable - ABCDE Is patient bleeding Has patient bled Does patient need transfusion What is the cause
When do you consider sideroblastic anaemia
If microcytic anaemia not responding to iron
What causes
Congenital X-linked = rare Myeloproliferative Lead poison Alcohol Chemo Anti-TB RT
What tests
Increased ferritin
Microcytic anaemia
Sideroblasts in marrow with
Papneheimer bodys (iron pooled in mitochondria)
Rx
Remove cause
What happens in sideroblast
Body has iron but can’t incorporate into Hb so deposited around mitochondria
What are the microangiopathic haemolytic anaemia’s (MAHA)
HUS
TTP
DIC
Due to endothelial layer of small blood vessel = disrupted leading to fragmentation of red cells and consumption of platelet
What do they all have in common
Thrombocytopenia
- Increased coagulation activation uses up platelet
Haemolytic anaemia
- Fibrin forms in arterioles and capillaries
- RBC get fragmented and sheared
- Schistocyte on film = sheared RBC
AKI (renal failure)
- Due to impact on renal vessel
What causes HUS
E.coli0157
Malignancy
What is typical picture
Bloody diarrhoea a few weeks before Anaemia Jaundice Bruising Oedema Hypertension
What will investigation show
Haemolytic anaemia Thrombocytopenia Renal failure Normal PT / APTT Film = schistocytes
How do you Rx
IV fluid
SUpportive
NO AX
What causes TTP
Coagulation problem (ADAMTS13 definceicy) Malignancy
What is typical picture
Same as HUS but also
FEVER
CNS - weakness / visual / seizure / LOC
How do you investigate
Same as HUS
Clinical differentiation
How do you Rx
Plasmapharesis and FFP
Specialist
Very very sick as red blood cells are bursting
What causes DIC
Sepsis
HELLP in pregnancy
Malignancy
How do you Ix
Thrombocytopenia
Raised PT / APTT
Low fibrinogen
Schistocyte on film
How does it present
Same as above Anaemia Jaundice Brusiing Oedema HYPOTENSION / SHCOK Decreased consciousness
What ar path-pneumonia for MAHA - microangiopathic
Schisocytes on film
What is Fanconi Anaemia
AR aplastic anaemia
What are features
Anaemia
Neuro Sx
Short stature
Cafe au lait
What are you at increased risk of
AML
