Anaemia Flashcards
IRON DEFICIENCY ANAEMIA - Causes
Iron deficiency anaemia is a very common problem both in the developed and developing world.
In the UK, the commonest causes are :
- Reduced dietary intake of iron due to junk food diets
- OR Impaired absorption from the GI tract because of malabsorption syndromes such as coeliac disease or pernicious anaemia.
- Other leading causes are blood loss from either the gastrointestinal or genitourinary tracts.
In the developing world, the leading cause of iron deficiency anaemia is parasitic infection.
IRON DEFICIENCY ANAEMIA - Mx
Management of iron deficiency anaemia is by diagnosis of the underlying cause and management of this, but also in replacement of the depleted iron stores.
Replacing depleted iron stores:
- The easiest and cheapest method of iron replacement is by oral iron supplementation in the forms of ferrous sulphate, ferrous fumarate, ferrous feredetate or ferrous gluconate. The sulphate form is cheapest but other forms have fewer irritant side effects on the stomach and duodenum and may be better tolerated.
Macrocytic Anaemia
Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow
Megaloblastic Causes of Macrocytic Anaemia
Vitamin B12 deficiency Folate deficiency (Metformin can also cause macroycitc anaemia due to its effects n folate metabolism, it's a folic acid antagonist)
Normoblastic Causes of Macrocytic Anaemia
alcohol liver disease hypothyroidism pregnancy reticulocytosis myelodysplasia drugs: cytotoxics
Macrocytic Anaemia - Example Question
A 44 year old male presents with a 2 month history of increasing lethargy. His wife reports him to be not quite himself for the past 2 months now, with poor oral intake and poor appetite. He is a self-employed software engineer but currently is unable to work due to his lethargy. He was previously treated for Hodgkin’s lymphoma 5 years ago and has since been in remission.
On examination, he has no conjunctival pallor, is dry on his mucous membranes and extremely lethargic. Firm, rubbery lymph nodes are noted in the right axilla. Cardiovascular examination reveals a soft systolic murmur, respiratory and abdominal examinations are unremarkable. He is a non-smoker and drinks alcohol only occasionally. His blood tests are as follows:
Hb 8.8 g/dl
MCV 104 fl
Platelets 94 * 109/l
WBC 12.8 * 109/l
Red cell distribution 9% (normal 11.5-14.5%)
Blood film leucoerythroblastic with myeloblasts
What is the cause of this patients anaemia?
B12 and folate deficiency Iron deficiency Anaemia of chronic disease Myelodysplasia post-chemotherapy > Marrow infiltration
This patient has a symptomatic macrocytic anaemia, of which B12 and folate deficiency, myelodysplasia post-chemotherapy and marrow infiltration could all be causes. Iron deficiency results in a microcytic anaemia while anaemia of chronic disease typically causes a microcytic or normocytic anaemia. Blood cells in B12 and folate deficiency are typically megaloblastic, large immature red cells caused by impaired DNA synthesis. Myelodysplasia typically results in red cells of abnormal shapes (poikilocytosis) and sizes (anisocytosis) with Pappenheimer bodies (abnormal granules of iron). Chemotherapy is a possible cause of myelodysplasia but typically after recent treatment only. Sadly in this case, the blood film of myeloblasts and erythroblasts suggests transformation of Hodgkin’s lymphoma into acute myeloid leukemia, a well recognised complication of Hodgkin’s lymphoma chemotherapy with older alkylating agents, typically 5 to 10 years after treatment.. Blast cells have now subsequently infiltrated the bone marrow, resulting in macrocytic anaemia.
Haemolytic Anaemia - Types
= HEREDITARY vs ACQUIRED
Hereditary Haemolytic Anaemia
Hereditary haemolytic anaemias can be subdivided into membrane, metabolism or haemoglobin defects
Hereditary causes
- membrane: hereditary spherocytosis/elliptocytosis
- metabolism: G6PD deficiency
- haemoglobinopathies: sickle cell, thalassaemia
Acquired Haemolytic Anaemia
Acquired haemolytic anaemias can be subdivided into immune and non-immune causes
Acquired: immune causes
- autoimmune: warm/cold antibody type
- alloimmune: transfusion reaction, haemolytic disease newborn
- drug: methyldopa, penicillin
Acquired: non-immune causes
- microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia
- prosthetic cardiac valves
- paroxysmal nocturnal haemoglobinuria
- infections: malaria
HUS-TTP (Haemolytic Uraemic Syndrome - thrombotic thrombocytopenia purpura spectrum)
Blood film with fragment red cells (schistocytes), thrombocytopaenia acute kidney injury, pyrexia and bloody diarrhoea, should strongly suggest haemolytic uraemia syndrome-thrombotic thrombocytopaenia purpura spectrum (HUS-TTP) in the absence of alternative unifying causes.
Microangiopathic Haemolytic Anaemia - Example Question
A 34 year old male presents with a 4 day history of bloody diarrhoea and vomiting, fevers and associated with occasional abdominal cramps. He reports no other symptoms. He reports no previous history of gastrointestinal disease; there is no family history of inflammatory bowel disease. He has no past medical history except for a left knee arthroscopy following an injury playing football 7 months ago. He is a lifelong non-smoker, drinks 14 units of alcohol a month, has not travelled abroad in the past year and last ate outside of his home a week ago during a barbecue at his brothers house.
On examination, he appears dehydrated. There is mild generalised abdominal tenderness with increased bowel sounds. Respiratory and cardiovascular examinations were unremarkable. His blood tests are as follows:
Hb 9.2 g/dl MCV 90fl Platelets 49 * 109/l WBC 14.2 * 109/l Neutrophils 12.8 * 109/l Blood film schistocytes, reticulocytosis Direct antiglobulin test negative Urea 14.9 mmol/l Creatinine 159 µmol/l CRP 82 mg/l
What is the cause of this patients blood abnormalities?
> Microangiopathic haemolytic anaemia Cold autoimmune haemolytic anaemia Warm autoimmune haemolytic anaemia Iron deficiency anaemia Acute myeloid leukemia
The first recognition in this patient is the underlying syndrome: blood film with fragment red cells (schistocytes), thrombocytopaenia acute kidney injury, pyrexia and bloody diarrhoea, should strongly suggest haemolytic uraemia syndrome-thrombotic thrombocytopaenia purpura spectrum (HUS-TTP) in the absence of alternative unifying causes. In this case, gastrointestinal infection by campylobacter from the recent barbecue, producing Shiga toxins and resulting in endothelial damage, is a strong possible culprit. The patient has a normocytic anaemia with red cell fragmentation and increased reticulocyte production, suggestive of rapid mechanical destruction and the bone marrow releasing immature red cells in (unsuccessful) compensation. This represents microangiopathic haemolytic anaemia (MAHA) in the context of HUS-TTP.
Both cold and warm autoimmune haemolytic anaemias should produce a positive direct antiglobulin test (Coombs): addition of a Coombs reagent containing antihuman globulin should agglutinate red cells IgM and IgG antibodies bound to in cold and warm autoimmune haemolytic anaemias respectively. Iron deficiency anaemia typically produces microcytic anaemias with target cells; there are no blast cells suggestive of leukemia.
Macrocytic Anaemia - Diagnosis: Example Question
A 67-year-old woman presents to her GP with progressive numbness and difficulty walking. Furthermore her daughter who was present mentions that she has been behaving strange over the past few months.
She is otherwise fit and well, apart from a ileal resection for treatment-resistant Crohn’s disease 9 years ago.
Laboratory tests showed a low haematocrit and mean corpuscular volume of 110 fL. Blood smear analysis noted macrocytic red blood cells with hypersegmented neutrophils.
Which of the following is the most likely cause of the patient’s presentation?
Ferrochelatase deficiency Folate deficiency Intrinsic factor deficiency Iron deficiency anaemia > Cobalamin deficiency
The ileal resection suggests that the patient is not absorbing the vitamin B12-intrinsic factor complex, leading to vitamin B12 deficiency (aka. cobalamin deficiency), and subsequently subacute combined degeneration. This is further supported by the macrocytic anaemia with hypersegmented neutrophils. Folate deficiency causes the same blood film picture but does not present with neurological symptoms.
Heinz Body Haemolytic Anaemia - Example Question
A 33 year old female presents to urgent care centre complaining of 4 days of increasing lethargy and reduced exercise tolerance. In addition, she reports dark urine but no other symptoms. She normally works as a clerical member of staff in the same hospital. Her only past medical history if ulcerative colitis, which before a flare 2 weeks ago requiring addition of sulphasalazine, had been well controlled with no immunosuppressants. On examination, you note conjunctival pallor bilaterally. Her abdomen is soft and non-tender. Her respiratory, cardiovascular and neurological examinations are unremarkable except for a mild systolic murmur and sinus tachycardia of 104 beats/ minute. Rectal examination was empty, no oral ulcers were noted.
Her blood tests are as follows:
Hb 8.9 g/dl MCV 85fl Platelets 356 * 109/l WBC 12.1 * 109/l Blood film Heinz bodies, reticulocytosis CRP 30 mg/l LDH 2400 u/l
What is the most appropriate immediate treatment?
Transfuse 2 units of packed red blood cells Start intravenous hydrocortisone, stop sulphasalazine Start intravenous hydrocortisone, continue sulphasalazine > Stop sulphasalazine only Urgent colonoscopy
The diagnosis of the underlying cause of anaemia is in the blood film: the patient has Heinz bodies, small inclusion bodies in red blood cells that are a consequence of usually oxidative damage to haemoglobin components. Note the close temporal association of the anaemia with starting sulphasalazine. Drugs such as sulphasalazine, dapsone, ribavirin and poisoning with paraquat ingestion leads to oxidation of Fe2+ (ferrous) components of haem to Fe3+ (ferric), forming methaemoglobin. When the intrinsic antioxidation mechanism of NADPH and glutathione is overwhelmed, red cell components undergo oxidative damage and cell death, leading to haemolysis, explaining the significantly raised LDH. Methaemoglobin is converted to hemichromes and eventually precipitated to Heinz bodies.
The treatment of oxidative haemolytic anaemia is by withdrawal of the offending drug alone. There is no role for steroids in this setting: the symptoms are not consistent with an ulcerative colitis flare. Blood abnormalities should normalise within weeks of drug withdrawal: transfusion of further red blood cells prior to stopping the drug would only result in further haemolysis.
Drug-induced Heinz Body Haemolytic Anaemia
Drugs such as sulphasalazine, dapsone, ribavirin and poisoning with paraquat ingestion leads to oxidation of Fe2+ (ferrous) components of haem to Fe3+ (ferric), forming methaemoglobin. When the intrinsic antioxidation mechanism of NADPH and glutathione is overwhelmed, red cell components undergo oxidative damage and cell death, leading to haemolysis, explaining the significantly raised LDH. Methaemoglobin is converted to hemichromes and eventually precipitated to Heinz bodies.
What are Heinz Bodies?
Heinz bodies are red cell inclusions consisting of denatured Hb; they are a feature of oxidative stress.
CKD Anaemia
Patients with chronic kidney disease (CKD) may develop anaemia due to a variety of factors, the most significant of which is reduced erythropoietin levels. This is usually a normochromic normocytic anaemia and becomes apparent when the GFR is less than 35 ml/min (other causes of anaemia should be considered if the GFR is > 60 ml/min). Anaemia in CKD predisposes to the development of left ventricular hypertrophy - associated with a three fold increase in mortality in renal patients
Causes of Anaemia in Renal Failure
Causes of anaemia in renal failure
reduced erythropoietin levels - the most significant factor
reduced erythropoiesis due to toxic effects of uraemia on bone marrow
reduced absorption of iron
anorexia/nausea due to uraemia
reduced red cell survival (especially in haemodialysis)
blood loss due to capillary fragility and poor platelet function
stress ulceration leading to chronic blood loss
CKD Anaemia - Mx
Management
the 2011 NICE guidelines suggest a target haemoglobin of 10 - 12 g/dl
determination and optimisation of iron status should be carried out prior to the administration of erythropoiesis-stimulating agents (ESA). Many patients, especially those on haemodialysis, will require IV iron
ESAs such as erythropoietin and darbepoetin should be used in those ‘who are likely to benefit in terms of quality of life and physical function’
One of the key points of treating patients with anaemia secondary to CKD revolves around the patient’s iron status. Nice guidelines recommend (in order of preference) these tests for determining a patient’s iron status and thus response to treatment:
1) % hypochromic red cells (requires analysis within 6 hours) a value of >6% indicates iron deficiency
2) Reticulocyte Hb content where < 29pg is diagnostic of iron deficiency anaemia
3) A combination of transferrin saturations (<20%) and ferritin (<100 micrograms/litre)
CKD Anaemia Mx - Example Question
You are seeing a 35 year old gentleman in outpatient renal clinic with known CKD5 (chronic kidney disease stage 5) as a consequence of analgesic induced nephropathy. He tells you that over the past few weeks he has been feeling increasingly tired and has noticed that he’s been having headaches. Asking more about his tiredness he states that he can get around his house, but has noticed increased shortness of breath when climbing the stairs. On examination it is clear that he has pale mucous membranes and a slightly hyperdynamic circulation.
Bloods taken from the morning are as follows:
Hb 82 g/l Platelets 154 * 109/l WBC 2.7 * 109/l Bilirubin 14 µmol/l ALP 154 u/l ALT 7 u/l Albumin 28 g/l Ferritin 350 ng/ml Transferrin saturations 24% B12 451 pg/ml Folate 4.8 nmol/nl TSH 2.1 mIU/L
How would you manage this patient’s anaemia?
Start ferrous fumarate 210mg three times daily Intravenous iron infusion guided by weight and Hb > Start an ESA (erythrocyte colony stimulating agent) Transfuse 1 unit of packed red cells Transfuse 1 unit of packed red cells then start an ESA (erythrocyte colony stimulating agent)
This question requires knowledge about investigating and treating anaemia in patients with CKD.
One of the key points of treating patients with anaemia secondary to CKD revolves around the patient’s iron status. Nice guidelines recommend (in order of preference) these tests for determining a patient’s iron status and thus response to treatment:
1) % hypochromic red cells (requires analysis within 6 hours) a value of >6% indicates iron deficiency
2) Reticulocyte Hb content where < 29pg is diagnostic of iron deficiency anaemia
3) A combination of transferrin saturations (<20%) and ferritin (<100 micrograms/litre)
From this definition the patient is not iron deficient and this will not receive suitable benefit from initiation of iron therapy whether oral or intravenous. So the decision revolves around the starting of an erythrocyte colony stimulating factor and whether to transfuse him. Transfusion alone is not sensible as this is not a suitable sustainable method of treating his anaemia. Because the patient is young and potentially transplantable, one should avoid transfusion unless necessary. Thus the best option in this patient is to start an erythrocyte colony stimulating agent.
