Haematology Flashcards
What would be blood results of anaemia of chronic disease?
low/normal ferritin and wide distribution of red blood cell volume
What are side effects of ferrous sulphate?
Black stools, constipation, diarrhoea, nausea
What are triggers for sickle cell crisis?
Infection, dehydration, hypoxia, acidosis, exposure to cold
Why does sickle cell not present till 6 months?
High levels of HbF mask the effect of this until they start to fall at 6 months
What are some complications of myeloma?
Hypercalcaemia, spinal cord compression, hyperviscosity, acute renal failure.
Why are people with myeloma susceptible to other infections?
Possible bone marrow infiltration; immunoparesis secondary to overexpression of one immunoglobulin and underexpression of any other immunoglobulins.
What is the treatment for CLL and how is it given?
Imatinib - tyrosine kinase inhibitor, oral
CML vs CLL
CLL - usually an incidental finding with no symptoms
CML - will have symptoms, usually massive splenomegaly (described as sense of fullness sometimes)
AML vs CML
AML - low neutrophils and platelets
CML - anaemia, raised neutrophils and platelets
ALL blood findings
- Raised lymphocytes
- Low neutrophils
- Low platelets
What is raised with beta thalassaemia major?
HbA2
PT vs APTT
PT - extrinsic - Factors 3 and 7 (play tennis outside)
APTT - intrinsic - Factors 9,11,13 (play table tennis inside)
New B symptoms in someone with CLL?
Richters transformation -> CLL transforms into aggressive large cell lymphoma
Patients over the age of 60 who present with iron deficiency anaemia
Investigate for colorectal cancer -> colonoscopy
Causes of the renal impairment in myeloma?
AL type amyloidosis, Bence Jones nephropathy, nephrocalcinosis, nephrolithiasis
Isolated rise in GGT in the context of a macrocytic anaemia
Alcohol excess
‘starry sky’ appearance on lymph node biopsy
Burkitt lymphoma - associated with EBV/HIV
Complications of blood transfusions
Non-haemolytic febrile reaction: Fever and chills -> slow/stop transfusion + paracetamol
Minor allergic reaction: urticaria and pruritic -> stop transfusion and give antihistamine
Acute haemolytic reaction: fever, abdominal pain, hypotension -> stop transfusion, recheck patient identity, send blood for repeat testing
Transfusion-associated circulatory overload: hypertension, pulmonary oedema -> slow/stop transfusion + loop diuretic and oxygen
Transfusion-related acute lung injury: hypoxia, hypotension, fever -> stop transfusion, oxygen
What is the most common clotting abnormality?
Von-Wilebrand disease
What is the treatment for beta thalassaemia major?
Lifelong blood transfusions
low platelets, increased clotting time and raised fibrin degradation products (FDPs)
DIC
When does heparin-induced thrombocytopenia present?
5-14 days post op with low platelets, nothing else
Which drugs can cause haemolytic in patients with G6PD?
- Ciprofloxacin
- Sulphasalazine
- Sulfonylureas
- Sulphonamides
Hereditary spherocytosis vs G6PD?
HS - extra vascular haemolysis -> causes splenomegaly
G6PD - intravascular haemolysis -> normal spleen
Inheritance of G6PD vs HS?
G6PD - X linked recessive -> transmitted from mother
HS - Autosomal dominant
What can precipitate renal failure in patients with myeloma?
NSAIDs
unexplained nosebleeds and menorrhagia + an immune condition
Think ITP
IgA deficiency increases the risk of what?
Anaphylactic reactions to blood transfusions
Which leukaemia is associated with polycythaemia?
AML
Blood test findings for leukaemia?
AML: increased myeloblasts + anaemia and thrombocytopenia
ALL: increased lymphoblasts + anaemia and thrombocytopenia
CML: increased granulocytes + anaemia
CLL: increased lymphocytes (usually B cells) + anaemia
What are negative prognostic factors for lymphoma?
- The presence of B symptoms
- Male gender
- Being aged >45 years old at diagnosis
- High WCC, low Hb, high ESR or low blood albumin
- Lymphocyte depleted subtype
What infection can trigger an aplastic crisis in patients with hereditary spherocytosis?
Parvovirus
Which subtype of Hodgkins has the best prognosis?
Lymphocyte predominant
Malaria prophylaxis can trigger what?
Haemolytic anaemia in those with G6PD deficiency
hyper-segmented neutrophil polymorphs
Megaloblastic anaemia
Abdominal pain, constipation, neuropsychiatric features, basophilic stippling
Lead poisoning
What are irradiated blood products used for?
Reduce the risk of graft vs host disease by destroying T cells
What are the adverse effects of tamoxifen?
Increased risk of VTE and endometrial cancer
Most common organism which causes neutropenic sepsis?
Staph epidermis
Which drugs can cause aplastic anaemia?
- Phenytoin
- Chloramphenicol
- Cytotoxics
- Sulphonamides
IgM paraprotein
Waldenstrom’s macroglobulinaemia
pain, oedema, dermatitis, ulceration, abnormal skin pigmentation, hyperpigmentation, gangrene, lipodermatosclerosis
post-thrombotic syndrome
When should G6PD enzyme assays be done?
At presentation and 3 months after to avoid false negatives
Mycoplasma infection can cause what?
Cold Autoimmune haemolytic anaemia
What ITU treatment could be considered for someone with sickle cell crisis
Exchange transfusion -> reduce number of sickle cells and increase normal RBC to improve oxygenation
What is a common complication of Burkitts lymphoma?
Tumour lysis syndrome
What electrolyte imbalances are seen in tumour lysis?
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
‘tear drop’ poikilocytes
Myelofibrosis
intense itching which usually occurs after exposure to hot water or hot and humid weather
Polycythaemia vera
What can be given prior to chemo to prevent tumour lysis syndrome?
Allopurinol or rasburicase
Beta thalasaaemia major vs trait?
Major would have profound anaemia usually Hb <60
Sickle cell + abdominal pain + anaemia
Sequestration crisis
Transfusion thresholds?
Normal patients <70
Patients with ACS <80
What is the treatment for ITP?
Oral steroids / IVIG if signs of major bleeding
Rouleaux formation
Multiple myeloma
Target cells and Howell-Jolly bodies
Coeliac disease -> hyposplenism
decrease in haptoglobin levels
Haemolysis
large multinucleate cells with eosinophilic nucleoli
Reed-Sternberg
What are complications of CLL?
- Anaemia
- Recurrent infections due to hypogammaglobulinaemia
- Warm AIHA
- Transformation into non-Hodgkins
High HBA2?
Beta thalassaemia
What is the treatment for post thrombotic syndrome?
Compression stockings
Complications of polycythaemia?
- Thrombotic events (patients given aspirin as prophylaxis)
- Myelofibrosis
- Acute leukaemia
normocytic anaemia with low serum iron, low TIBC but raised ferritin
Think anaemia of chronic disease
Aplastic crisis vs sequestration crisis in sickle cell?
Aplastic - reduced reticulocytes
Sequestration - increased reticulocytes
Thalassaemias will cause what?
Haemolysis -> raised bilirubin
Management of anti-phospholipid in pregnancy?
Aspirin + LMWH
What is the reversal agent for dabigatran?
Idarucizumab
Myeloma Investigations
Bloods - anaemia
Blood film - rouleaux formation
Urine protein electrophoresis - Bence Jones (IgA/IgG)
Bone marrow - Raised plasma cells
CXR/MRI - osteolytic lesions
What mutation would be seen in polycythaemia?
JAK-2
How does heparin work?
Activate antithrombin III - measure APTT
Elderly patient with fatigue, splenomegaly, weight loss/night sweats?
Think myelofibrosis
‘myeloid blast’ cells are suggestive of what?
AML
What are signs of low Hb on examination?
Pallor, tachycardia, tachypnoea, flow murmur
What are causes of late transfusion complications?
Iron overload, graft versus host disease, post transfusion purpura, infection
What is a massive blood transfusion?
Transfusion of 10 units/a patients entire blood volume within 24 hours
How to test for pernicious anaemia?
Intrinsic factor - most useful
gastric parietal cell antibodies
Pernicious anaemia predisposes to what?
Gastric cancer
How is haemophilia inherited?
X linked recessive
What is the most common inherited thrombophilia?
Factor V Leiden deficiency
small, single, peripherally-located, rounded inclusion in 50-60% of the erythrocytes.
Howell-Jolly body -> Hyposplenism
Metallic aortic valves can cause what?
Non-immune haemolytic anaemia
What can be given to reduce the frequency of sickle cell crises?
Hydroxycarbamide (hydroxyurea)
How to manage high INR in patients needing emergency surgery?
Give IV Vit K and recheck INR in 6-12 hours
If surgery cannot be postponed give 4 factor prothrombin + IV Vit K to reverse warfarin
What is a safe INR for surgery?
<1.5
What organisms are people with sickle cell susceptible to?
Strep pneumoniae
TACO vs TRALI
TACO - SOB and hypertension
TRALI - hypotension
What is the management of ITP?
Emergency: Platelet transfusion/IV Methylpred/IVIG
Platelet > 30 - Observe
Platelet <30 - Oral pred
What are features of blood film post splenectomy?
Howell- Jolly bodies
Pappenheimer bodies
Target cells
Irregular contracted erythrocytes
finger abduction weakness
Lesion at T1
TPP Symptoms?
- Fever
- Neuro symptoms
- Renal failure
- Anaemia
- Low platelets
ITP VS TTP VS DIC
DIC will have raised PT/INR/APTT + low platelets whereas for ITP and TTP this will be normal
How can tumour lysis syndrome be diagnosed?
- Increased serum creatinine
- Cardiac arrhythmia
- Seizure
Aplastic crisis vs sequestration
Aplastic - sudden fall in Hb after parvovirus infection
Sequestration - sickling within organs such as spleen/lungs causing pooling of blood
Polycythaemia + sudden drop in Hb?
AML
Isolated rise in Hb?
Polycythaemia
Bite and blister cells
G6PD deficiency
What is the main management of sickle cell crises?
- IV analgesia, fluids + oxygen
- Consider Abx if infection and blood transfusion if Hb is low
ITP vs VWD?
ITP - destruction of platelets so platelet count is low with normal PT and APTT
VWD - platelets are fine but they take longer to stop bleeding so platelet count is normal, PT and APTT are prolonged
Hand foot mouth syndrome - sudden swelling, pain and erythema?
Think Sickle cell disease
How is tranexamic acid given followng major haemorrhage?
IV bolus followed by slow infusion
anisocytosis, macrocytosis and hyposegmentation of the neutrophils.
Myelodyplastic syndrome -> can progress to AML
Over how long are RBC transfused?
90-120 minutes in non urgent cases
Microcytic anaemia with high ferritin + transferrin saturation?
Think sideroblastic anaemia - basophilic stippling
Warm vs Cold AIHA?
Warm - IgG - associated with CLL
Cold - IgM (M for Mountains - cold) - associated with lyMphoma / Mycoplasma / EBV
What is the pathological process behind myeloma?
Clonal proliferation of plasma cells with paraprotein production
What is the treatment for myeloma?
- Chemo
- Bisphosphonates often given for bone protection
What translocation causes Philadelphia?
t(9:22) - gene BCR/ABL
What blood test will be raised with Hodgkins?
LDH
Why does sickle cell often present in >1ys?
Fetal Hb protects against sickling therefore by 1 transformation to adult haemoglobin is completed
What is the action of LMWH?
Anti-thrombin and anti-Xa
What are the best blood tests to examine synthetic liver function?
INR and albumin
What does cryoprecipitate contain?
Factor 8, VWF, fibrinogen and factor 13
What does plasma contain?
All clotting factors
What is the pathophysiology of DIC?
- Diffuse thrombin activation by a trigger which activates coag cascade
- This leads to platelet consumption and clotting factor consumption
What are triggers for DIC?
- Sepsis
- Trauma
- Malignancy
- Vasculitis
- Toxins
- Pancreatitis
Beta thalassaemia major vs trait?
Major - homozygous mutation, Trait - heterozygous mutation
What may be seen on blood film in beta thalassaemia?
- Basophilic stippling
- Microcytosis
- Hypochromic red cells
What should be given to patients with beta thalassaemia major with blood transfusion?
Desferrioxamine
What blood abnormality does warfarin cause?
Prolonged PT, normal APTT
Which organisms cause post splenectomy sepsis?
- Strep pneumoniae
- H influenzae
- Meningococci
All patients with IHD should take what?
Aspirin
Warfarin can rarely cause what?
Skin necrosis
Ileocecal resection can result in what?
Vit B12 deficiency
How can painful vaso-occulsive crises be diagnosed?
Clinically
DIC is associated with what?
Schistocytes
Men of any age with a Hb below 110g/L should what?
Refer for upper and lower GI endoscopy as 2 week wait
What is the reversal agent for heparin overdose?
Protamine sulphate
What is the management of heparin induced thrombocytopenia?
If anticoag needed, switch to direct thrombin inhibitors e.g. argatroban
Prosthetic heart valves can cause what?
Haemolytic anaemia
pain when exposed to cold, jaundice, anaemia?
Sickle cell
platelet count < 30 x 109 and clinically significant bleeding
Platelet transfusion needed
Raised haemoglobin, plethoric appearance, pruritus, splenomegaly, hypertension
Polycythaemia
Haemoarthroses (bleeding in joints) are a sign of what?
Haemophilia
Transfusions can cause what?
Hyperkalaemia and hypocalcaemia
Investigations for polycythaemia?
- FBC/Blood film
- JAK2 mutation
How often should sickle cell patients receive the PCV vaccine?
Every 5 years
Reversal for rivaroxaban and apixaban
andexanet alfa
Macrolides can cause what?
Drug induced neutropenia
Sideroblastic anaemia vs iron deficiency?
Sideroblastic - high ferritin and serum iron levels
What is the definitive investigation for sickle cell?
Haemoglobin electrophoresis
Dry tap bone marrow aspirate?
Think primary myelofibrosis
How is sideroblastic anaemia inherited?
X linked
What does rituximab target?
CD20
ADAMTS-13 deficiency is associated with what?
TTP
Blood film showing Schistocytes?
AIHA
Target cells with asymptomatic anaemia?
Beta thalassaemia trait
Non Hodgkins vs CLL
CLL - significant lymphocytosis
Anaemia with raised bilirubin + LDH?
Haemolytic anaemia
What is permissive hypotension?
A strategy in bleeding of trauma patients where you use less fluids and maintain lower BP to prevent clots
What are electrolyte imbalances following large blood transfusion?
- Hyperkalaemia
- Hypocalcaemia
- Iron overload
Blood film changes
Target cells - Iron deficiency anaemia, sickle cell, hyposplenism, liver disease
Spherocytes - spherocytosis, AIHA
Basophilic stippling - lead poisoning, thalassaemia, sideroblastic anaemia
Heinz bodies - G6PD
Schistocytes - G6PD, DIC
Pencil poilkilocytes - Iron deficiency
Management of AIHA
- Supportive care
- Steroids to suppress immune system
- Splenectomy in severe cases
What happens to EPO in polycythaemia?
Reduces
Schistocytes will be seen in what?
Haemolysis
Raised red cell distribution width?
Think mixed deficiency e.g iron and folate
Recurrent DVTs in someone already on a DOAC?
Increase dose, check adherence or switch to another anticoagulant e.g. warfarin
Increased concentration of haemltocrit is what?
Polycythaemia
Major haemorrhage protocol involves providing what?
Packed red cells, platelets and FFP
Blood oozing from a cannula site is a classic sign of what?
DIC
<40 year old with raised platelets but no raised Hb?
Essential thrombocytopenia
Types of autoimmune haemolytic anaemia (AIHA)?
‘warm’ and ‘cold’ types according to what temp the antibodies best cause haemolysis
Causes of autoimmune haemolytic anaemia (AIHA)?
idiopathic most common
secondary to lymphoproliferative disorder, infection or drugs
Ix for autoimmune haemolytic anaemia (AIHA)?
+ve direct antiglobulin test (Coombs’ test)
- anaemia
- reticulocytosis
- low haptoglobin
- raised LDH and indirect bilirubin
- blood film: spherocytes and reticulocytes
What does blood film for autoimmune haemolytic anaemia show?
spherocytes and reticulocytes
What test is specific for autoimmune haemolytic anaemia?
positive direct antiglobulin test (Coombs’ test)
Warm AIHA?
most common type
the antibody (IgG) causes haemolysis best at body temp and haemolysis tends to occur in extravascular sites, for example the spleen
Causes of warm AIHA?
- idiopathic
- autoimmune disease eg. SLE
- neoplasia: lymphoma, CLL
- drugs eg. methyldopa
Mx of warm AIHA?
- Tx underlying disorder
- steroids +/- rituximab 1st line
Cold AIDA?
usually IgM and causes haemolysis best at 4 deg C
haemolysis is mediated by complement and is more commonly intravascular
Features of cold AIHA?
Raynaud’s and acrocyanosis
Mx of cold AIHA?
respond less well to steroids
Causes of cold AIHA?
- neoplasia: lymphoma
- infections: mycoplasma, EBV
SLE can rarely be associated with what?
mixed-type autoimmune haemolytic anaemia
most commonly warm AIHA
Types of haemolytic anaemias (causes)?
- Autoimmune= cold and warm AIHA
By cause…
- Hereditary= membrane, metabolism (G6PD def), haemoglobinopathies (sickle cell, thalassaemia)
- Acquired= immune and non-immune
By site….
- Intravascular haemolysis
- Extravascular haemolysis
Hereditary haemolytic anaemias can be subdivided into what?
membrane, metabolism or haemoglobin defects
Hereditary causes of haemolytic anaemia?
- membrane= hereditary spherocytosis/elliptocytosis
- metabolism= G6PD def
- haeemoglobinopathies= sickle cell, thalassaemia
Acquired haemolytic anaemias can be subdivided into what?
immune and non-immune causes
Acquired immune causes of haemolytic anaemia, are they Coombs-positive or negative?
positive
Acquired non-immune causes of haemolytic anaemia, are they Coombs-positive or negative?
negative
Acquired immune causes of haemolytic anaemia (Coombs-positive)?
- autoimmune= cold/warm antibody type
- alloimmune= transfusion reaction, haemolytic disease newborn
- drug= methyldopa, penicillin
Acquired non-immune causes of haemolytic anaemia (Coombs-negative)?
- microangiopathic haemolytic anaemia (MAHA)= TTP/HUS, DIC, malignancy, pre-eclampsia
- prosthetic heart valves
- paraoxysmal nocturnal haemoglobinuria
- infections= malaria
- drug= dapsone
- Zieve syndrome
Zieve syndrome?
rare clinical syndrome of Coombs-negative haemolysis, cholestatic jaundice, and transient hyperlipidaemia associated with heavy alcohol use, typically following a binge
typically resolves with abstinence from alcohol
What happens in intravascular haemolysis?
free Hb is released which then binds to haptoglobin
as haptoglobin becomes saturated Hb binds to albumin forming methaemalbumin (detected by Schumm’s test)
free Hb is excreted in urine as haemoglobinuria, haemosiderinuria
Intravascular haemolysis causes?
- mismatched blood transfusion
- G6PD def (is elements of extravascular but classed still as intra)
- red cell fragmentation: heart valves, TTP, DIC, HUS
- paroxysmal nocturnal haemoglobinuria
- cold autoimmune haemolytic anaemia
Extravascular haemolysis causes?
- haemoglobinopathies: sickle cell, thalassaemia
- hereditary spherocytosis
- haemolytic disease of newborn
- warm autoimmune haemolytic anaemia
What is haemolytic anaemia?
condition where RBCs are destroyed faster than bone marrow can produce them; called haemolysis and can lead to shortage of RBCs
causes symptoms like fatigue, weakness, SOB
can be inherited or acquired
Intrinsic vs extrinic haemolytic anaemia?
Intrinsic= caused by defects within RBCs usually due to genetic mutations affecting the cell’s membrane, enzymes, or hemoglobin. These structural or functional abnormalities make RBCs more prone to breaking down prematurely.
Extrinsic= RBC destruction is due to external factors acting on otherwise normal cells, such as autoimmune attacks, mechanical damage, infections, or toxic exposure.
Intravascular vs extravascular haemolysis?
Intravascular= destruction of RBCs occurs within blood vessels; more abrupt and can lead to severe symptoms due to rapid release of Hb into blood eg. jaundice, severe- kidney damage
Extravascular= RBCs destroyed outside blood vessels primarily in spleen or liver; slower and occurs when macrophages in spleen identify RBCs as abnormal and break them down. Less likely to cause haemoglobinuria or kidney damage; splenomegaly, jaundice and anemia over time
Lab findings in intravascular haemolysis (haemolytic anaemia) vs extravascular?
Intravascular= high LDH, low haptoglobin, haemoglobinuria, haemoglobinaemia
Extra= elevated indirect bilirubin and LDH, low or normal haptoglobin, increased reticulocyte count as bone marrow tries to compensate
Iron def occurs as a result of what?
long-term negative iron balance
Iron def spectrum?
ranges from iron depletion to iron def anaemia
Iron def anaemia?
diminished RBC production due to low iron stores in the body
Anaemia definition?
Hb level two standard deviations below the normal for age and sex
Anaemia in men aged over 15yrs?
Hb below 130g/L
Anaemia in non-pregnant women aged over 15yrs?
Hb below 120g/L
Anaemia in children aged 12-14yrs?
Hb below 120g/L
Anaemia in pregnant women?
Hb below 110g/L throughout pregnancy.
Hb level of 110g/L or more appears adequate in 1st trimester
Level 105g/L appears adequate in 2nd and 3rd trimesters
Anaemia in postpartum women?
below 100g/L
Causes of iron def anaemia?
often mutlifactorial
- dietary def
- malabsorption
- increased loss
- or increased requirements
Symptoms of iron def anaemia?
fatigue, dyspnoea, headache
cognitive dysfunction, restless leg syndrome
dizziness/lightheaded
weakness
dysgeusia
irritability
pica eg. ice
pruritus
sore tongue
palpitations
tinnitus
impairment of body temp regulation (preg women)
Signs of iron def anaemia?
pallor, atrophic glossitis
dry and rough skin dry and damaged skin
less common= tachycardia, nail changes (koilonychia), angular cheilosis
diffuse and moderate alopecia
worsening of pre-existing tachy, murmurs, cardiac enlargement and HF is anaemia severe (Hb <70)
may be no signs even if severe
What biochemical test most reliably correlates with relative total body iron stores?
serum ferritin
Diagnosis of iron def anaemia?
serum ferritin level less than 30 micrograms/L confirms diagnosis
Why are ferritin levels difficult to interpret when diagnosing iron def anaemia?
if infection or inflam present, levels can be high even in presence of iron def
ferritin levels may be less reliable in pregnancy
What is important to determine and treat in pt presenting with iron def aneamia?
underlying cause
When to urgently refer pt with iron def anaemia?
suspected ca pathway for colorectal ca if they have a faecal immunochemical testing (FIT) result of at least 10 micrograms of Hb per g of faeces
When to refer to gastroenterology for pt with iron def anaemia?
All men and postmenopausal women with iron deficiency anaemia unless they have overt non-gastrointestinal bleeding.
Men with a Hb level <120 g/L and postmenopausal women with an Hb level <100 g/L should be investigated more urgently, as lower levels of Hb suggest more serious disease.
All people aged 50 yrs+ with marked anaemia, or a significant Fx of colorectal carcinoma, even if coeliac disease is found.
Premenopausal women if they are aged <50yrs and have colonic symptoms, a strong Fx of GI ca, persistent iron def anaemia despite treatment, or if they do not menstruate.
When to refer women to gynaecology if present with iron def anaemia?
- menorrhagia unresponsive to medical Mx
- postmenopausal= 55yrs+ urgent suspected ca pathway; <55yrs consider urgent suspected ca pathway
Pt <50yrs with rectal bleeding (and iron def anaemia)?
consider urgent referral
What should be considered in iron def anaemia in premenopausal women with Hx of menorrhagia or pregnant women (if no suspicion of coeliac disease)?
Diagnostic trial of iron Tx for 2-4w
Do not do this for men and postmenopausal women
What to exclude in pt with iron def anaemia who is a man or postmenopausal?
GI sources of bleeding
Mx of iron def anaemia?
- all pts= 1 tablet OD of oral ferrous sulfate, ferrous fumarate or ferrous gluconate- continue for 3m after iron def corrected to allow stores to be replenished
- if not tolerated then 1 tablet on alternate days or alternative oral preparation
- parenteral iron if contraindicated or ineffective
- DO NOT WAIT for Ix before prescribing
- Monitor to ensure response
- Refer when appropriate
How to check response to Mx in iron def anaemia?
- Hb levels (FBC) checked 2-4w to assess response
Pt with iron def anaemia who has had oral ferrous sulfate (oral iron Mx); when should they undergo specialist assessment?
if lack of response (increase of less than 20g/L in Hb level) after 2-4w
What may suggest underlying GI bleeding resulting in iron def anaemia?
recent illness
GI disorders
colorectal carcinoma
What pts with iron def anaemia may have few symptoms?
pt with chronic, slow blood loss may be able to tolerate v low levels of Hb (eg. less than 70g/L)
Slow onset iron def anaemia?
may have no or very few symptoms eg. fatigue, mild SOB after exertion
Very common and common symptoms of iron def anaemia?
V common= dyspnoea, fatigue, headache
Common= cognitive dysfunction, restless leg syndrome
Rare symptoms of iron def anaemia?
- dysphagia (in association with oesophageal web which occurs in Patterson-Brown-Kelly or Plummer-Vinson syndromes).
- Haemodynamic instability
- syncope
Symptoms of iron def without anaemia?
fatigue, lack of concentration, irritability
Serious symptoms of iron def anaemia eg. if Hb is <70g/L?
worsening pre-existing anginal pain, ankle oedema, dyspnoea at rest
indicates additional heart or lung pathology
Nail changes in iron def anaemia?
longitudinal ridging
koilonychia (spoon-shaped nails)
Angular cheilosis?
ulceration of corners of mouth
in iron def anaemia
Angular cheilosis and koilonychia?
iron def anaemia
Ix for iron def anaemia?
- FBC
if show low Hb and low MCV.. - check ferritin level (less reliable in preg) (<30 micrograms/L)
- total iron binding capacity (high- reflects low iron stores) and a low transferrin
- blood film
- can do vit B12 and folate too (esp if older age as more risk of pernicious anaemia)
MCV in iron def anaemia?
likely if MCV is <95 femotolitres
Red blood cell changes associated with iron def anaemia?
- microcytosis (low MCV)
- reduced mean cell Hb (hypochromia)
- increased % of hypochromic red cells
- anisocytosis (variation in size of RBCs)
- poikilocytosis (presence of irregulary shaped RBCs)
Anisocytosis?
variation in size of RBCs
Poikilocytosis?
presence of irregularly shaped RBCs
Pregnant women and suspect iron def anaemia?
- FBC is routine in preg
- may do blood film
Blood film in iron def anaemia in pregnant women?
microcytic hypochromic red cells and characteristic ‘pencil cells’
hypochromia may also occur in haemoglobinopathies (eg. thalassaemia)
Physiological reduction in Hb conc in pregnancy?
does not represent anaemia
increase in red cell mass and plasma volume, plasma vol increases more than red cell mass, leading to haemodilution and fall in haematocrit from 40% to 33%
Normal pregnancy is associated with what?
- physiological reduction in Hb conc (doesn’t mean anaemia)
- slight increase in MCV (approx 4 femtolitres)
When might MCV not fall below the normal range in iron def anaemia?
in milder cases of iron def anaemia
What level of serum ferritin level confirms diagnosis of iron def anaemia?
<30 micrograms/L
When are ferritin levels increased independently of iron status?
in acute and chronic inflam conditions, malignant diease, liver disease
infection
Serum ferritin conc of what level indicates iron depletion in all stages of pregnancy? When should Tx be considered?
<15 micrograms/L
Tx should be considered when levels fall below 30 micrograms/L, as this indicates early iron depletion which will continue to fall unless treated
What should be considered as 1st line diagnostic test for normocytic or microcytic anaemia in pregnant women with no haemoglobinopathy?
oral iron trial
if known haemoglobinopathy check serum ferrritin before starting
(if unknown need NHS sickle cells and thalassaemia screening programme)
Diagnosed with iron def anaemia, what Ix should you then do to determine the cause?
- coeliac serology (anti-TTG)
- test urine for blood
- FIT
- stool exam if travel Hx to detect parasites
When is Ix to determine underlying cause for iron def anaemia not necessary?
- young pt with Hx suggesting cause eg. regular blood donor
- menstruating young women no Hx of GI symptoms or FHx colorectal ca
- pregnant unless severe anaemia, no response to iron or exam & Hx suggest alternative cause eg. IBD
- terminally ill pts or unable to undergo Ix eg. Mx would not be influenced by results
- pts who refuse
Differential diagnosis of microcytic anaemia?
TAILS
- Thalassaemia
- Anaemia of chronic disease (80% normocytic and normochromic but can be microcytic, hypochromic anaemia )
- Iron def
- Lead poisoning eg. exposure to lead paint
- Sideroblastic anaemia (very rare)
How to describe type of anaemia in iron def anaemia?
microcytic, hypochromic anaemia
Differential diagnosis of normocytic anaemia?
AAA HH
A.naemia of chronic disease
A.cute blood loss
A.plastic anaemia
H.aemolytic anaemia
H.ypothyroidism
(also CKD)
Microcytic anaemai?
MCV <80
problem producing RBCs or Hb
MCV stands for?
mean capsular volume
Normocytic anaemia?
MCV 80-95 (normal)
increase destruction of RBCs
Macrocytic anaemia?
MCV >95
Macrocytic anaemia?
Megaloblastic= B12 & folate def
Non-Megaloblastic= liver disease, alcohol, drugs, reticulocytosis, hypothyroidism
Megaloblastic macrocytic anaemia?
impaired DNA synthesis; megaloblasts present
Non-megaloblastic macrocytic anaemia?
erythrocytes normal
Why do tests in Thalassaemia and sideroblastic anaemia show an increase in serum iron and ferritin, with a low total iron-binding capacity?
both associated with an accumulation of iron
When to refer women to obstetrics with iron def anaemia?
significant symptoms and/or severe anaemia (haemoglobin less than 70 g/L), if pregnancy is at advanced gestation (over 34 weeks), or if there is failure to respond to a trial of oral iron.
Pt with iron def anaemia, initially responded to iron Tx but develops anaemia again without an obvious cause?
refer
Should iron replacement therapy be given whilst awaiting Ix for iron def anaemia?
yes unless colonoscopy imminent
Dietary iron advice if iron def anaemia if thought to be cause?
dark green vegetables, iron-fortified bread, meat, apricots, prunes and raisins
consider referral to dietitian
Aim of Tx in iron def anaemia?
restore Hb levels and red cell indices to normal, and to replenish iron stores
Dose of elemental iron (as ferrous sulfate) oral for iron def anaemia?
65mg elemental iron (ferrous sulfate 200mg) OD on empty stomach
do not recommend perparations that contained iron combined with folic acid, vit B12 or other nutrients
Advice to give pt who is taking iron supplements?
- may get adverse effects but usually settle with time, important to be compliant
- if get GI adverse effects, can be minimised by taking with or after food or reducing dose to alternate days
- explain monitoring requirements
- safe storage eg. if have young children as overdose can be fatal
Monitoring for pt being Tx for iron def anaemia?
- Hb within 1st 4w; Hb should rise by 20 over 3-4w
- then check FBC at 2-4m to check Hb returned to normal
- once Hb conc and red cell indices normal= continue iron for 3m then stop
- monitor FBC periodically= 3,6,12 and 24m
- if drop then prescribe iron supplements; consider prophylactic dose in pt who risk of iron def anaemia
When may an ongoing prophylactic dose of iron (200mg ferrous sulfate daily) be beneficial in pt with iron def anaemia?
- recurring anaemia eg. elderly and further Ix not appropriate or indicated
- diet unlikely to meet daily iron eg. plant based diets
- malabsorption eg. coeliac
- menorrhagia
- had gastrectomy
- pregnant
- undergoing hameodialysis
How to manage pt if inadequate response to initial iron Tx in iron def anaemia?
- assess compliance
- adress adverse effects
- specialist advise
- refer if lack of response after 2-4w : If the person has already had normal upper and lower gastrointestinal Ix for iron deficiency anaemia and the anaemia persists or recurs, consider testing for Helicobacter pylori, and eradicate if present
Adverse effects and how to manage in pt taking oral iron supplement for iron def anaemia?
- constipation= laxative
- black stools= reassure
- recommend to take iron with or after meals
- reduce dose frequency to alternative days
- consider alternative oral preparations
Why does iron def lead to reduction in RBCs/Hb (anaemia)?
iron needed to make Hb in RBCs
Iron def anaemia has highest incidence in who?
preschool aged children
Main causes of iron def anaemia?
XS blood loss, inadequate dietary intake, poor intestinal absorption, increased iron requirements
Most common cause of anaemia?
iron def
Eg. of XS blood loss causing iron def anaemia?
menorrhagua
GI bleeding (suspected colon ca)
What conditions can lead to poor iron absorption?
conditions affecting small bowel eg. coeiliac disease
Why may children or pregnant women get iron def anaemia?
increased iron requirements
children= increased demands due to growth
pregnant= supply for baby; also increase in plasma vol causes dilution of iron (proportion of fluid in comparison to RBCs increases)
Koilonychia?
spoon shaped nails
iron def anaemia
What does FBC demonstrate in iron def anaemia?
hypochromic microcytic anaemia
What does hypochromic anaemia mean?
when RBCs appear plaer than normal due to reduced levels of Hb
often associated with microcytic RBCS
High total iron-binding capacity (TIBC) reflects…
low iron stores
Blood film for iron def anaemia?
anisopoikilocytosis (RBCs of diff sizes and shapes), target cells and ‘pencil’ polikilocytes
Males and post-menopausal women who present with unexplained iron def anaemia should be considered for what?
endoscopy to rule out ca
Post-men women Hb ≤10 and men ≤11 refer to gastro for this within 2w
Common side effects of iron supplements?
nausea, abdo pain, constipation, diarrhoea
Iron def anaemia: serum iron, TIBC, transferrin saturation and ferritin?
Serum iron= low <8
TIBC= High
Transferrin sat= low
Ferritin= low
Anaemia of chronic disease: serum iron, TIBC, transferrin saturation and ferritin?
Serum iron= low <15
TIBC= low
Transferrin sat= low
Ferritin= High
Why is there low serum iron in iron def anaemia?
Serum iron reflects the amount of circulating iron in the blood. In iron deficiency anemia, there’s a lack of iron
Why in iron def anaemia is the TIBC high?
TIBC is a measure of the blood’s capacity to bind iron, largely determined by transferrin, the main protein that transports iron in the bloodstream. In iron deficiency, the liver increases transferrin production to maximize iron transport and absorption from dietary sources. This results in a high TIBC, indicating an increased iron-binding capacity in the blood.
In iron def anaemia, why is the transferrin saturation low?
Transferrin saturation is calculated by dividing serum iron by TIBC. In iron deficiency anemia, both low serum iron and high TIBC contribute to a low transferrin saturation. This low saturation means that only a small percentage of transferrin is bound to iron, indicating a lack of available iron for the body’s needs.
In iron def anaemia, why is the ferritin low?
Ferritin is the main storage protein for iron, and low ferritin levels indicate depleted iron stores in the body. It is one of the earliest indicators of iron deficiency, as the body first draws on stored iron before serum iron levels begin to drop.
Megaloblastic causes of macrocytic anaemia?
vit B12 def
folate def
eg. secondary to methotrexate
Normoblastic (non-megaloblastic) causes of macrocytic anaemia?
alcohol
liver disease
hypothyroidism
preg
reticulocytosis
myelodysplasia
drugs: cytotoxins
History of a normal Hb level associated with microcytosis?
In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra vera which may cause an iron-deficiency secondary to bleeding.
New onset microcytic anaemia in elderly pts?
urgently Ix to exclude malignany
In beta-thalassaemia minor, the microcytosis is often…
disproportionate to the anaemia
Under homeostatic conditions (normal balanced), the process of coagulation and fibrinolysis are coupled (work alongside eachother). Explain this?
1) Coagulation Activation= the coagulation cascade is triggered, producing thrombin that then converts fibrinogen into fibrin, forming a stable fibrin clot- the final product of hemostasis
2) Fibrinolysis= the break down fibrinogen and fibrin. When the fibrinolytic system is activated, plasmin is generated (in presence of thrombin) which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products).
3) Role of plasmin= in a state of homeostasis, the presence of plasmin is critical- it is the central proteolytic enzyme of coagulation and necessary for fibrinolysis.
Explain the coagulation cascade?
1) Intrinsic pathway
- trigger= Activated by damage within the blood vessel or when blood comes into contact with negatively charged surfaces, such as collagen exposed by vessel injury.
- Process:
1. Begins with Factor XII (Hageman factor), which becomes activated upon contact with the damaged vessel.
2. Activated Factor XII (XIIa) activates Factor XI.
3. Activated Factor XI (XIa) then activates Factor IX.
4. Factor IXa, with the help of Factor VIII and calcium ions, activates Factor X.
- Result: The intrinsic pathway leads to the activation of Factor X, which then moves into the common pathway.
2) Extrinsic pathway
-trigger: Activated by external trauma that causes blood to escape from the blood vessels, exposing tissue factor (TF), a protein not normally in contact with blood.
- process:
1. Tissue damage exposes tissue factor, which binds with Factor VII in the blood.
2. The TF-Factor VII complex activates Factor X.
- Result: This pathway provides a rapid response to trauma, directly activating Factor X and feeding into the common pathway.
3) Common Pathway
- trigger: Both the intrinsic and extrinsic pathways activate Factor X, which is central to the common pathway.
- process:
1. Activated Factor X (Xa), along with Factor V and calcium ions, converts prothrombin (Factor II) to thrombin (Factor IIa).
2. Thrombin then converts fibrinogen (a soluble protein) into fibrin (an insoluble protein), forming a mesh-like structure that stabilizes the clot.
3. Thrombin also activates Factor XIII, which cross-links fibrin strands, strengthening the clot.
- Result: The formation of a stable fibrin clot, which effectively stops bleeding at the injury site.
What is the coagulation cascade?
complex series of steps involving clotting factors that work together to form a blood clot, which prevents bleeding after injury.
Cascade can be divided into 3 main pathways: intrinsic, extrinsic and common/ These activate in response to diff types of damage but all coverge to produce a stable fibrin clot.
Role of thrombin in coagulation cascade?
Converts fibrinogen to fibrin
How does clot stabilsation occur in the coagulation cascade?
Factor XIII cross-links fibrin strands, creating a strong, stable clot.
Summarise the body’s response to vessel injury? (Hemostasis)
1) Vasoconstriction= reduces blood flow to injury site
2) Platelet plug formation= provides initial seal and a surface for clot formation
3) Coagulation cascade= produces thrombin and fibrin to form a stable clot
4) Clot retraction and fibrinolysis= breakdown fibrin mesh into fibrin degradation products using plasmin, gradually removing the clot and restoring normal blood flow
Describe the platelet plug formation that occurs after vessel injury (in primary hemostasis)?
1) When vessel is injured, the endothelium (inner layer of vessel wall) exposes the underlying collagen and von Willebrand factor (vWF)
2) Platelet circulating in the blood bind to vWF and adhere to the exposed collagen anchoring them to the injury site
3) Upon adhesion, platelets become activated, change shape to increase surface area and release chemical signals (ADP, thromboxane A2 and serotonin) that recruit more platelets to the injury
4) These chemicals also make the platelets ‘sticky’ promoting further aggregation
5) Platelet aggregation= activated platelets bind together, forming a temporary platelet plug that covers the wound
6) Platelet plug provides initial seal to stop small injuries from bleeding and creates surface for coagulation cascade to occur
(coagulation cascade activated also by damage that forms a stable fibrin clot that securely seals the injury)
Hemostasis?
body’s process of stopping bleeding at site of blood vessel injury
Stages of hemostasis?
1) Vasoconstriction
2) Primary hemostasis (platelet plug formation)
3) Secondary hemostasis (coagulation cascade and clot formation)
then once vessel healed
4) Fibrinolysis to dissolve the clot
What happens in disseminated intravascular coagulation (DIC)?
processes of coagulation and fibrinolysis are dysregulated= widespread clotting with resultant bleeding
DIC pathophysiology in different conditions?
Regardless of what causes/triggers DIC, once initiated the pathophysiology is similar in all conditions
Critical mediator of DIC?
the release of a transmembrane glycoprotein (tissue factor=TF)
What is tissue factor (TF)?
present on surface of many cell types (incl endothelial cells, macrophages and monocytes) and is not normally in contact with general circulation (blood); but it is exposed to circulation after vascular damage
What plays a major role in the development of DIC in septic conditions?
TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor and endotoxin.
Why may DIC readily develop in patients with extensive trauma?
As TF is abundant in tissues of the lungs, brain and placenta.
Pathophysiology of DIC?
1) DIC trigged by massive release of TF into blood eg. due to sepsis, severe trauma, malignancy
2) When TF released in large amounts, it binds with factor VII and activates extrinsic pathway, then activates factor X and then thrombin generated.
3) The thrombin generated: activates additional clotting factors (XI and VIII) in intrinsic pathway, this amplifies the clotting process leading to activation of intrinsic pathway. Thrombin also activates platelets - provide surface for further clotting factor activation supporting both I and E pathways.
4) Upon activation of DIC, tissue factor binds with coagulation factors that then trigger the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.
5) This cross activation becomes pathological as both E and I pathways are continuously activated without regulation.
6) Results in widespread clot formation in small vessels throughout body, consuming platelets and clotting factors. Eventually body depletes clotting components and leafs to risk of severe bleeding (clotting factors become exhausted).
DIC: why does the extrinsic pathway trigger the instrincic?
extrinsic pathway triggers the intrinsic pathway due to an overwhelming and inappropriate activation of the coagulation system. This widespread activation leads to clotting throughout the body rather than being localized at an injury site.
(As the extrinsic pathway triggers massive thrombin generation, it overflows into the intrinsic pathway, causing continuous activation of clotting factors.)
Why in DIC do you get systemic imbalance where both haemorrhage and thrombosis occur simultaneously?
The body attempts to break down clots through fibrinolysis, which releases fibrin degradation products (FDPs), further impairing clotting. Combination of clotting and bleeding.
Causes of DIC…
- sepsis
- trauma
- malignancy
- obstetric complications eg. HELLP syndrome, amniotic fluid embolism
What is the reason for example sepsis or trauma may cause DIC?
Due to trauma or sepsis (or other causes) a massive release of tissue factor is released into bloodstream (normally should not be in contact with blood) and activates coagulation cascade (extrinsic pathway).
TF may be released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin.
Typical blood picture of DIC?
↓ platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
schistocytes due to microangiopathic haemolytic anaemia
What does DIC stand for?
disseminated intravascular coagulation
Prothrombin time, APTT, bleeding time and platelet count in warfarin administration?
PT= prolonged
APTT= normal
Bleeding time= normal
Platelet count= normal
Prothrombin time, APTT, bleeding time and platelet count in aspirin administration?
PT= normal
APTT= normal
Bleeding time= prolonged
Platelet count= normal
Prothrombin time, APTT, bleeding time and platelet count in heparin administration?
PT= often normal (may be prolonged)
APTT= prolonged
Bleeding time= normal
Platelet count= normal
Prothrombin time, APTT, bleeding time and platelet count in DIC?
PT= prolonged
APTT= prolonged
Bleeding time= prolonged
Platelet count= low
What is PT (prothrombin time)?
assesses the extrinsic and common pathways of the coagulation cascade, specifically measuring how long it takes blood to clot.
Factors Involved: PT primarily reflects the activity of Factors I (fibrinogen), II (prothrombin), V, VII, and X.
Use: Often used to monitor warfarin therapy and diagnose liver disease, vitamin K deficiency, or bleeding disorders that affect the extrinsic pathway.
Normal Range: Typically 11-13.5 seconds, although ranges may vary between laboratories.
A prolonged PT suggests what?
deficiencies in factors of the extrinsic pathway or issues in the common pathway
What is APTT (activated partial thromboplastin time or PTT)?
evaluates the intrinsic and common pathways of the coagulation cascade, measuring the time it takes for blood to clot when stimulated by a specific activator.
Factors Involved: APTT reflects the function of Factors VIII, IX, XI, and XII in the intrinsic pathway, as well as Factors I, II, V, and X in the common pathway.
Use: Commonly used to monitor heparin therapy and diagnose bleeding disorders related to the intrinsic pathway, such as hemophilia.
Normal Range: Usually between 25-35 seconds, but this varies by laboratory.
Prolonged APTT can indicate what?
deficiencies in intrinsic pathway factors or the presence of an inhibitor (like lupus anticoagulant).
What is bleeding time?
assesses platelet function and the ability of blood vessels and platelets to form a primary hemostatic plug.
Factors Involved: Reflects platelet function and interactions with the blood vessel wall, rather than specific clotting factors.
Use: Used less frequently today, but it may help diagnose platelet function disorders, such as von Willebrand disease or thrombocytopathy (platelet dysfunction).
Normal Range: Typically 2-7 minutes.
Prolonged bleeding time suggests what?
defect in platelet function or blood vessel integrity, not coagulation factors.
What is platelet count?
measure of the number of platelets in the blood, expressed in thousands per microliter (μL).
Factors Involved: Directly reflects platelet quantity rather than their functionality.
Use: Helps diagnose conditions with abnormal platelet levels, such as thrombocytopenia (low platelets) or thrombocytosis (high platelets).
Normal Range: Usually 150,000 to 450,000 per μL.
Low platelet count (thrombocytopenia) may be seen in what? High?
Low platelet count (thrombocytopenia) may be seen in bone marrow disorders, immune thrombocytopenia, or disseminated intravascular coagulation (DIC).
High platelet count (thrombocytosis) may occur with chronic inflammation, certain cancers, or post-splenectomy.
Difference between PT and APTT?
PT:
- pathways tested= extrinsic and common
- factors measured=Factors I (fibrinogen), II (prothrombin), V, VII, and X
- trigger of test= Measures clotting after adding tissue factor
- uses= Monitors warfarin therapy; screens for liver disease or extrinsic pathway deficiencies
- normal range= 11-13.5 seconds (often reported as INR)
- interpretation of prolongation= Prolonged in vitamin K deficiency, liver disease, or Factor VII deficiency
APPT:
- pathways tested= intrinsic and common
- factors measured= Factors VIII, IX, XI, XII and Factors I, II, V, and X
- trigger of test= measures clotting after adding activator and calcium
- uses= monitors heparin therapy; identifies intrinsic pathway deficiencies such as hemophilia
- normal range= typically 25-35 seconds
- interpretation of prolongation= prolonged in hemophilia, Factor VIII, IX, XI, or XII deficiencies, or heparin therapy
What is PT and APTT used to monitor?
PT is used to monitor warfarin
APTT is used to monitor heparin
What pathway does warfarin affect? (anticoag)
extrinsic
What pathway does heparin affect (anticoag)?
intrinsic
Prolonged PT vs prolonged APTT?
PT= Prolonged in vitamin K deficiency, liver disease, or Factor VII deficiency
APTT= Prolonged in hemophilia, Factor VIII, IX, XI, or XII deficiencies, or heparin therapy
Haemochromatosis?
autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation
Inheritance of haemochromatosis?
autosomal recessive
What causes haemochromatosis?
inheritance of mutations in HFE gene on both copies of chromosome 6
Symptoms in early disease in haemochromatosis?
often asymptomatic in early disease and initial symptoms non-specific eg. lethargy and arthralgia
Epidemiology of haemichromatosis?
1 in 10 people of European descent carry a mutation in the genes affecting iron metabolism, mainly HFE
prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis
Features of haemochromatosis?
- early= fatigue, erectile dysfunction, arthalgia (often of hands)
- ‘bronze’ skin pigmentation
- diabetes mellitus
- liver: hepatomegaly, cirrhosis, hepatocellular deposition, stigmata of chronic liver disease
- cardiac failure
- hypogonadism
- arthritis (esp of hands)
Features of the liver in pts with haemochromatosis?
stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition
Why do pts with haemochromatosis get heart failure?
secondary to dilated cardiomyopathy
Why do pts with haemochromatosis get hypogonadism?
secondary to cirrhosis and pituitary dysfunction- hypogonadotrophic hypogonadism
Reversible Cx of haemochromatosis (reversible with Tx)?
- cardiomyopathy
- skin pigmentation
Irreversible Cx of haemochromatosis (can’t be Tx)?
- liver cirrhosis (LFTs and hepatomegaly may be reversible but cirrhosis is not)
- DM
- dypogonadotrophic hypogonadism
- arthropathy
Fatigue, erectile dysfunction, bronze skin pigmentation, DM, arthritis of hands and hepatomegaly?
haemochromatosis
Autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation?
haemochromatosis
Ix for haemochromatosis?
Screen for iron overload:
- iron profile= transferrin sat, ferritin (not usually abnormal in early stages)
- genetic testing for HFE mutation in family members
Other tests:
- LFTs
- molecular genetic testing for C282Y and H63D mutations
- MRI: quantify liver and/or cardiac iron
- liver biopsy if suspected hepatic cirrhosis
