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.
Pernicious Anaemia - Epidemiology
Epidemiology
more common in females (F:M = 16:1)
typically develops in middle to old age
more common if blood group A
Pernicious Anaemia - Pathophysiology
Pathophysiology
autoimmune disease caused by antibodies to gastric parietal cells or intrinsic factor
results in vitamin B12 deficiency
associated with thyroid disease, diabetes, Addison’s, rheumatoid and vitiligo
predisposes to gastric carcinoma
Pernicious Anaemia - Features
Features
lethargy, weakness
dyspnoea
paraesthesia
also: mild jaundice, diarrhoea, sore tongue
possible signs: retinal haemorrhages, mild splenomegaly, retrobulbar neuritis
Pernicious Anaemia - Mx
Treatment of the disorder is with 3 monthly treatment of vitamin B12 injections. Folic acid supplementation may also be required.
Pernicious Anaemia - Autoimmune Disease
Autoimmune diseases, in this case pernicious anaemia, are more likely in the presence of another autoimmune disease (rheumatoid arthritis). Pernicious anaemia is an autoimmune condition that targets the parietal cells of the gastric lining, the role of which is to produce intrinsic factor. Intrinsic factor is responsible for the absorption of vitamin B12. In this case, a lack of B12 has led to a macrocytic anaemia as seen with the high MCV. To diagnose pernicious anaemia blood can be tested for parietal cell antibodies and intrinsic factor antibodies. These supersede the classical test Schilling Test.
Pernicious Anaemia - Diagnosis: Example Question
A 60-year-old female patient is receiving etanercept for long term rheumatoid arthritis. She attends the general medical clinic with increasing shortness of breath on exertion. She has received treatment for arthritis for many years and has in the past received methotrexate. This was stopped due recurrent infections. She has had no recent courses of steroids. Her symptoms of arthritis are well controlled on her current treatment regimen.
On examination the patient had a blunted affect. Her tongue appeared mildly swollen and red with some area of soreness at the corners of her mouth. She did not exhibit finger clubbing but the nails appeared brittle. Her pulse was 92 bpm and her blood pressure 106/68 mmHg. Examination of her cardiorespiratory system revealed normal heart sounds with no added sounds and the occasional fine crepitation in her lung fields.
Basic investigations such as blood tests and a chest x-ray were undertaken. Results are shown below.
Hb 8.2 g/dl MCV 109fl Haematocrit 0.39 Platelets 380 * 109/l WBC 9.4 * 109/l
Renal function normal
Liver function normal
CXR normal
> Pernicious anaemia Sideroblastic anaemia Anaemia of chronic disease Iron deficiency anaemia Aplastic anaemia
The patient in this case demonstrated glossitis and angular chelitis with brittle nails that are associated with this condition. Her blunted affect is a sign of mild cognitive impairment that can also be present. The signs and symptoms of pernicious anaemia are vast and there frequency in clinical practice can be varied. Often the only presentation is with the fatigue associated with the anaemia.
It should be noted that another treatment for rheumatoid arthritis, Methotrexate, can induce another type of macrocytic anaemia. This is due to it inhibiting DNA replication in the same way as heavy metals such as lead.
B-12 Deficiency Anaemia: Example Question
A 68-year-old female, presents with lethargy and anorexia. She underwent a partial gastrectomy 3 years ago for bleeding gastric ulcer. Her blood results showed:
Hb 90 g/l MCV 109 fL Platelets 60 * 109/l WBC 3.5 * 109/l Blood film Oval erythrocytes, macrocytic erythrocytes, hypersegmented neutrophils, low platelets and basophilic stippling
What is the underlying diagnosis?
Sideroblast anaemia Spur cell haemolysis > Vitamin-B12 deficiency Thalassaemia Myelodysplasia
Gastrectomy is defined as partial when a part of the stomach is removed surgically and as total when the entire stomach is removed. Typical indications are gastric cancer, recurrent gastric ulcers, large duodenal perforations, bleeding gastric ulcers and gastrointestinal stromal tumours. Malnutrition is less common after partial than after total gastrectomy, but the key nutritional deficiencies are iron-deficiency anaemia, calcium deficiency, and vitamin B12 deficiency. However, the hypersegmented neutrophils are strongly suggestive of B12 deficiency.
Hypersegmented neutrophils are hallmarks of B12 deficiency in multiple choice questions.
Autoimmune Haemolytic Anaemia
Autoimmune haemolytic anaemia (AIHA) may be divided in to ‘warm’ and ‘cold’ types, according to at what temperature the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs. AIHA is characterised by a positive direct antiglobulin test (Coombs’ test)
Warm AIHA
Warm AIHA
In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen. Management options include steroids, immunosuppression and splenectomy
Causes of warm AIHA
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
*systemic lupus erythematosus can rarely be associated with a mixed-type autoimmune haemolytic anaemia
Cold AIHA
Cold AIHA
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
NB Acrocyanosis is blueness of the extremities (the hands and feet). Acrocyanosis is typically symmetrical. It is marked by a mottled blue or red discoloration of the skin on the fingers and wrists and the toes and ankles. Profuse sweating and coldness of the fingers and toes may also occur.
Sideroblastic Anaemia
= a condition where red cells fail to completely form HAEM
Incomplete biosynthesis of Haem takes place partly in the mitochondrion and consequently deposits of iron in the mitochondria form a ring around the nucleus called a ring ‘sideroblast’
May be congenital or acquired
Congenital causes = Delta-aminolevulinate synthase-2-deficiency
Acquired causes:
- myelodysplasia
- alcohol
- lead
- anti-TB meds
Ix:
- Hypochromic microcytic anaemia
- Bone marrow = sideroblasts and increased iron stores
Mx:
- Supportive
- Treat any underlying cause
- PYRIDOXINE may help (vit B6)
Haemolytic Anaemia by Site - Intravascular
In intravascular haemolysis, free Hb is released which 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:
- Mismatched blood transfusion
- G6PD Deficiency
- Red cell fragmentation
- Paroxysmal Nocturnal Haemoglobinuria
- Cold AIHA (when its cold you want stay inside!)
Haemolytic Anaemia - Extravascular
- Haemoglobinopathies: > Sickle Cell > Thalassaemia - Hereditary spherocytosis - Haemolytic disease of the newborn - Warm AIHA
Aplastic Anaemia - Mx
Supportive:
- Blood products
- Prevention and treatment of infection
Anti-Thymocyte Globulin (ATG) and Anti-Lymphocyte Globulin (ALG):
- Prepared in animals (e.g. rabbits or horses) by injecting human lymphocytes
- Highly allogenic and may cause serum sickness (fever, rash, arthralgia) therefore steroid cover usually given
- Immunosuppression using agents such as Cyclosporin may be given
Stem Cell Transplantation:
- Allogeneic transplants have success rate of upto 80%
Differentials of Microcytic Anaemia
1) Iron Deficiency
Ix = Transferrin, Ferritin
2) Thalassaemia
Ix = Haemoglobin Electrophoresis
3) Sideroblastic Anaemia (ineffective erythropoiesis leading to poor incorporation of iron into nucleus of erythroblasts)
Ix = Perl’s Stain > Shows ring sideroblasts
Precipitant = Isoniazid
4) Lead Poisoning!
IDA
Features:
- Koilonychia = spoon nails
- Atrophic glossitis = sore dry tongue
- Post cricoid webs = in Plummer Vinson Syndrome
- Angular stomatitis = erythema and maceration of skin adjacent to angle of mouth
Blood Film:
- Target cells
- ‘Pencil’ poikilocytes
- If combined with B12/Folate deficiency, a ‘dimorphic’ film occurs w mixed macrocytic and microcytic cells
Hereditary Spherocytosis - TRIAD
NORMOCYTIC ANAEMA + GALLSTONES + FHx
Hereditary Spherocytosis
Basics:
- Most common hereditary haemolytic anaemia in people of Northern European Descent
- Autosomal dominant defect of RBC cytoskeleton
- Normal biconcave disc is replaced by sphere shape
- RBC survival reduced as destroyed by spleen
Presentation:
- FTT
- Jaundice/gallstones
- Splenomegaly
- Aplastic crisis (precipitated by Parvovirus infection)
- MCHC elevated
Diagnosis:
- Osmotic Fragility Test
Mx:
- Folate replacement
- Splenectomy
Pernicious Anaemia Ix
Ix:
- anti gastric parietal cell antibodies in 90% (but low specificity)
- anti-intrinsic factor antibodies in 50% (specif for pernicious anaemia)
- macrocytic anaemia
- low WCC and platelets
- LDH may be raised due to ineffective erythropoiesis
- also low serum B12
- hypersegmented polymorphs on film and megaloblasts in marrow
- Schilling Test
Schilling Test:
- Radiolabelled B12 given on 2 occasions
1) First on its own
2) Second with ORAL INTRINSIC FACTOR
3) Urine B12 is measured each time
Myelodysplasia - Cause of Macrocytic Anaemia: Blood Film
Myelodysplasia typically results in red cells of abnormal shapes (poikilocytosis) and sizes (anisocytosis) with Pappenheimer bodies (abnormal granules of iron).
AIHA and Coombs Test
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 (cold) and IgG (warm) antibodies in haemolytic anaemia
Microangiopathic haemolytic anaemia (MAHA):
Examples of MAHA:
- TTP/HUS
- DIC
- Malignancy
- Pre-eclampsia
Macrocytic Anaemia: MEGALOBLASTIC CAUSES
Causes of megaloblastic anaemia
The liver has abundant stores of vitamin B12 and so, if absorption is impaired, it takes 4 or 5 years for deficiency to develop.
Vitamin B12 deficiency due to:
Autoimmune Addisonian pernicious anaemia (80%).
Potential after-effects of surgery - eg, gastrectomy or ileal resection.
Bacterial overgrowth or parasitic infestation.
HIV infection.
Dietary deficiency, which may occur in strict vegans but, even in them, it is rare.
Pernicious anaemia, which tends to be a disease of the elderly but, rarely, it can occur in the newborn, usually when there is deficiency in the mother.[4]
Folate deficiency due to:
Dietary deficiency.
Malabsorption.
Increased demands including haemolysis, leukaemia and rapid cell turnover as may occur in some skin diseases. Macrocytosis but without anaemia will develop in 30% of women in late pregnancy unless they take folic acid supplements.
Increased urinary excretion occurs in heart failure, acute hepatitis and dialysis.
Drug-induced deficiency includes alcohol, anticonvulsants, methotrexate, sulfasalazine and trimethoprim but only if high-dose and a prolonged course.
Macrocytic Anaemia: NON MEGALOBLASTIC CAUSES
Causes of non-megaloblastic macrocytosis
Alcohol abuse is a common cause. There may also be folate deficiency due to a poor diet although beer is a good source of folate.
Liver disease.
Severe hypothyroidism.
Reticulocytosis.
Other blood disorders including aplastic anaemia, red-cell aplasia, myelodysplastic syndromes, myeloid leukaemia.
Drugs that affect DNA synthesis, such as azathioprine.
Hypersegmented Neutrophils on Blood Film
Hypersegmented neutrophils are hallmarks of B12 deficiency in multiple choice questions.
Key Nutritional Deficiencies after a partial/total Gastrectomy
More significant after total gastrectomy but KEY deficiencies of both:
- iron-deficiency anaemia
- calcium deficiency
- vitamin B12 deficiency.
Heinz Body Anaemia = Oxidative Stress Anaemia - Drug Causes
Sulfasalazine
Dapsone
Ribavirin
Paraquat Poisoning
IDA - Ix = Combination of?
An iron deficiency anaemia picture is generally diagnosed by a combination of:
1) Low serum iron
2) High TIBC
3) Low ferritin.
Or Low Transferrin <20%, Low Ferritin <100mcg/L
Evan’s Syndrome
Evan’s Syndrome
- ITP in association with autoimmune haemolytic anaemia (AIHA)
