Anaemia Flashcards
1
Q
What is anaemia defined as?
A
Hb two standard deviations below mean for age and sex. Less than 13 g/dL for men over 15, and more than 12 g/dL in women.
2
Q
What is the normal range for MCV?
A
80-96 fl
3
Q
What is microcytic anaemia?
A
Anaemia associated with low MCV (less than 80)
4
Q
What is the aetiology of microcytic anaemia? (x5 (x5, x3, x5))
A
- IRON DEFICIENCY: most common cause; from reduced absorption (small bowel disease, post-gastrectomy), increased demand (growth or pregnancy), reduced intake (vegans), increased loss (GI tract, urogenital tract, menstruation), or hookworm infection. Leading to defect in HAEM SYNTHESIS.
- ANAEMIA OF CHRONIC DISEASE: usually normocytic; occurs in chronic inflammatory or autoimmune disease. Leading to defect in HAEM SYNTHESIS.
- THALASSAEMIA. Leading to defect in GLOBIN synthesis.
- SIDEROBLASTIC ANAEMIA: abnormality of haem synthesis. Can be X-linked recessive or secondary to alcohol, drugs, lead or myelodysplasia (bone marrow dysplasia). Leading to defect in HAEM SYNTHESIS.
- LEAD POISONING: interferes with globin and haem synthesis; in scrap metal or smelting workers.
5
Q
What is the process of iron metabolism?
A
Iron is lost through menstrual bleeding, sweating, skin desquamation, and urinary/faecal excretion. The body replenishes iron stores by recycling iron from destroyed/senescent RBCs and regulating dietary intake and absorption. Dietary iron is absorbed mostly in the duodenum and jejunum where it is transported by transferrin and stored in either ferritin or haemosiderin forms.
6
Q
What is the pathophysiology of iron deficiency anaemia?
A
Haemoglobin formation and RBC formation are impaired resulting in hypochromic and microcytic RBCs.
7
Q
What is the pathophysiology of anaemia of chronic disease?
A
- Inflammation/infection/autoimmune disease cause release in pro-inflammatory cytokines and subsequent changes in intracellular iron metabolism.
- One of these changes is up-regulation of hepcidin synthesis. Hepcidin inhibits iron transport by binding to the iron export channel ferroportin on basal surface of enterocytes. Hepcidin also causes iron-trapping in macrophages, splenic sequestration of iron, and impaired bone marrow responsiveness to erythropoietin.
- Another change is up-regulation of ferritin transcription
- Finally, ACD also reduces RBC lifespan die to increased erythrophagocytosis from raised macrophages
8
Q
What is the pathophysiology of lead poisoning?
A
- Lead poisoning is a SLOW process
- It competes with minerals, particularly calcium and zinc, therefore inhibiting many of these processes. Lead is mostly stored in in bones, nervous system and kidneys. Hence, toxicity typically observed in these systems:
- It interferes with calcium-dependent processes in the brain, resulting in deranged neurotransmitter function and Protein kinase C inhibition which may contribute to neurotoxicity
- Potent toxin in proximal renal tubules resulting in Fanconi’s syndrome
- Competing with zinc inhibits several enzymes involved in haem synthesis
- Lead interferes with mitochondrial function in vitro by interfering with calcium uptake
- Also perpetuates hypertension
9
Q
What is the pathophysiology of sideroblastic anaemia?
A
It is a form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy RBCs. In sideroblastic anemia, the body has iron available but cannot incorporate it into Hb, which red blood cells need in order to transport oxygen efficiently.
10
Q
What is the epidemiology of microcytic anaemia: Common?
A
Most common form of anaemia worldwide.
11
Q
What are the symptoms of microcytic anaemia? (x5)
A
Tiredness, dyspnoea, pallor, exacerbation of pre-existing angina or intermittent claudication. Pica in 55% of patients with iron-deficiency anaemia (unusual cravings for non-foods like dirt, ice, paint)
12
Q
What are the signs of microcytic anaemia? (x5)
A
- Pallor of skin and mucous membranes
- Brittle nails and hair. Koilonychia if long-standing
- Glossitis
- Cheilitis (angular stomatitis)
- Signs of thalassaemia
13
Q
What are the signs and symptoms of lead poisoning? (x9)
A
Anorexia, nausea + vomiting, abdominal pain, constipation, peripheral nerve lesions (foot and wrist drop), blue gumline, encephalopathy, convulsions, decreased consciousness.
14
Q
What are the blood investigations for microcytic anaemia?
A
FBC: low Hb, MCV, MCH, MCHC, haematocrit and reticulocytes
15
Q
How do you differentiate between IDA, lead poisoning, ACD and sideroblastic anaemia with blood investigations?
A
- Iron deficiency: low serum iron, ferritin, transferrin, high iron binding capacity.
- ACD: WBC and platelets may be raised, low serum iron, IRON BINDING CAPACITY, transferrin, high FERRITIN.
- Lead poisoning: high serum lead
- Sideroblastic anaemia: high IRON, FERRITIN, TRANSFERRIN, low total iron binding capacity
16
Q
How does microcytic anaemia present on blood film: IDA? ACD? Sideroblastic anaemia? Lead poisoning?
A
- IDA/ACD: microcytic, hypochromic (central pallor), anisocytosis (variable cell size), poikilocytosis (variable cell shape)
- SIDEROBLASTIC: dimorphic blood film (two populations of cells – one population normal and one population hypochromic, microcytic)
- LEAD POISONING: basophilic stippling (coarse dots represent condensed RNA in the cytoplasm)
17
Q
What is an additional investigation for microcytic anaemia?
A
Hb electrophoresis: for thalassemia, and presence of ring sideroblasts in the bone marrow in sideroblastic anaemia (iron deposited in mitochondria of erythroblasts, stain blue-green with Perl’s stain).
18
Q
What investigations should be ordered if IDA in post-menopausal women and over 40 years? (x3)
A
Upper GI endoscopy, colonoscopy, and investigations for haematuria to rule out blood loss cause.
19
Q
How is IDA managed? (x4)
A
Oral iron supplements (ferrous sulphate). Consider parenteral when oral not tolerated or malabsorption. Ascorbic acid promotes absorption of non-haema iron. Transfusion indicated if cardiac compromise.
20
Q
How is sideroblastic anaemia managed? (x4)
A
Treat cause (stop the causative drugs). Pyridoxine can be used if the disease is inherited. Consider blood transfusion and iron chelation (remember it is associated with high iron) if no response.
21
Q
How is lead poisoning managed? (x3)
A
Remove the source, dimercaprol and Ca2+ EDTA or D-penicillamine (lead chelation therapy).
22
Q
What are the complications of microcytic anaemia?
A
High cardiac output heart failure, complications of the cause.
23
Q
What is normocytic aneamia?
A
Low Hb associated with normal MCV (between 80 and 96 fl).
24
Q
What are the classifications of normocytic anaemia? (x2)
A
- HYPERPROLIFERATIVE (reticulocyte count over 2%) – the proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction/loss of RBCs. Cause is usually ACUTE blood loss of haemolysis.
- HYPOPROLIFERATIVE (reticulocyte count below 2%) – primarily in disorders of decreased RBC production
25
What is the aetiology of normocytic anaemia? (x4 (x5))
* BLOOD LOSS
* FAILURE OF PRODUCTION: such as in early stages of iron deficiency and ACD, renal failure from lack of erythropoietin, aplastic anaemia from bone marrow failure or suppression, bone marrow infiltration (cancer)
* HYPERSPLENISM: can be from liver cirrhosis leading to pooling of red cells in the spleen
* HAEMOLYTIC ANAEMIA
26
What is the epidemiology of normocytic anaemia: Aetiology is most common? Age?
Anaemia of chronic disease is the most common. Increased prevalence with age.
27
What are the investigations for normocytic anaemia?
Peripheral blood smear: reticulocyte count is done to determine cause. High reticulocyte count signifies bone marrow processes are normal; low reticulocyte count would signify there is a problem with the bone marrow which produces the stem cells.
28
How is normocytic anaemia treated? (x3)
* If aetiology is ACD, then treat cause first
* Erythropoietin may be considered if anaemia is severe – to stimulate the bone marrow to make more blood cells
* Blood transfusions in acute management
29
What is macrocytic anaemia?
Anaemia associated with high MCV of erythrocytes (at least 96 fl)
30
What is the aetiology of macrocytic anaemia? (x2)
* MEGALOBLASTIC: defect in DNA synthesis or maturation resulting in appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation
* NON-MEGALOBLASTIC: encompasses all other causes in which DNA synthesis in normal.
31
What is the aetiology of megaloblastic anaemia? (x3)
Vitamin B12 deficiency and Folate deficiency. Also, some drugs that interfere with DNA synthesis such as cancer drugs for leukaemia.
32
What is the aetiology of non-megaloblastic anaemia? (x8)
Alcohol excess, liver disease, myelodysplasia, multiple myeloma, hypothyroidism, haemolytic anaemia (shift to immature red cells: reticulocytosis), drugs (tyrosine kinase inhibitors: imatinib, sunitinib), aplastic anaemias (usually inherited aetiologies).
33
What are the possible mechanisms of macrocytic anaemia? (x2)
1. Results from ABNORMAL HEMOPOIESIS, so the red blood cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally. As a result, the red cells end up larger than normal. 2. Premature release of cells from the bone marrow. Young red blood cells are about 20% larger than mature RBCs, so if there’s an increased number of these premature cells (reticulocytes), then MCV is increased.
34
What is a megaloblast?
An abnormal bone marrow erythroblast (precursor of an erythrocyte with a nucleus). It is larger than normal and shows nucleocytoplasmic dissociation i.e. the maturation of the cytoplasm is mismatched with maturation of nucleus e.g. cytoplasm with dense Hb, but nucleus not condensed. NB: Megaloblastic refers to changes that occur ONLY in the BONE MARROW, but you can SEE the consequences of the megaloblastic changes by studying peripheral blood.
35
REMINDER: What is the process of RBC maturation?
PROERYTHROCYTES have large, Hb-producing nucleus, which disappears and leaves behind a nucleus-lacking cell RETICULOCYTE which matures into an erythrocyte.
36
How do you differentiate between megaloblastic and non-megaloblastic on FBC?
Megaloblastic has pancytopenia.
37
What are the roles of vitamin B12? (x2)
* Required for DNA synthesis.
* Integrity of the nervous system.
38
What are the roles of folic acid (folate)? (x2)
* DNA synthesis.
* Homocystine metabolism (homocysteine is a sulfur amino acid involved in remethylation and transsulfuration).
39
What is folate?
Vitamin B9, also known as folic acid.
40
How are vitamin B12 and folic acid involved in DNA synthesis?
Both are needed for the production of deoxythymidine which is a crucial building block in DNA synthesis.
41
What is the mechanism of absorption of folate?
Mostly absorbed in jejunum, with decreasing absorptive gradient into the colon. It is first cleaved by an enzyme on the intestinal brush border before absorption.
42
What is the aetiology of folate deficiency? (x5)
* Lack of dietary intake: green leafy vegetables, legumes and fruits. Or from consumption of unfortified cereals or excess cooking (destroying folate)
* Intestinal malabsorption: diseases of the small intestine (CD, Coeliac, resection)
* Infections: abnormal bacterial flora, tropical sprue (disease of malabsorption), fish tapeworm.
* Genetic: rare
* Drugs: alcohol, sulfasalazine, trimethoprim, methotrexate
43
What are the risk factors for folate deficiency? (x1, x6 and x2)
* Over 65 years old
* INCREASED DEMAND in pregnancy, lactation, malignancy, chronic inflammation, chronic haemolysis, exfoliative dermatitis (disease of high epithelial cell turnover, so demand on folate for DNA synthesis higher).
* INCREASED LOSS from chronic dialysis, and chronic haemolytic disorders.
44
What is the mechanism of absorption of Vitamin B12?
B12 is released from dietary sources by PEPTIC ACID. Most B12 is then absorbed by combining with an intrinsic factor made in the stomach by parietal cells. Once bound, the B12-IF complex that is formed can bind to ileal receptors and is absorbed.
45
What is the aetiology of Vitamin B12 deficiency? (x4)
* Lack of dietary intake: animal and dairy products, Vitamin B12 is stored in the liver for years, so B12 deficiency depends on chronic, long-term deficiency
* Malabsorption: (1) reduction in IF (gastrectomy, gastric atrophy or antibodies to intrinsic factor or parietal cells), (2) diseases of ileum such as CD, Coeliac or resection
* Infections: abnormal bacterial flora
* Drugs: PPIs (diminish breakdown in stomach), metformin (decrease intestinal absorption), OCP
46
What are the risk factors for Vitamin B12 deficiency? (x3)
* Over 65 years old
* Vegans
* History of gastric/intestinal surgery
47
What is pernicious anaemia?
Autoimmune condition associated with severe lack of intrinsic factor required for absorption of Vitamin B12. Therefore, it is an anaemia of vitamin B12 deficiency.
48
What are the autoimmune causes of pernicious anaemia? (x2)
Intrinsic factor antibodies or parietal cell antibodies – parietal make up 90% of pernicious anaemia cases.
49
What is the epidemiology of megaloblastic anaemia: Age? Gender?
Elderly and females.
50
What are the symptoms of Vitamin B12 and folate deficiency? Note about B12!
* NON-SPECIFIC SIGNS OF ANAEMIA: tiredness, lethargy, dyspnoea, headache
* Symptoms of the cause e.g., diarrhoea from tropical sprue
* FOLATE: severe deficiency can cause mucosal inflammation leading to dysphagia
* VITAMIN B12: unlike folate, may also present without peripheral neuropathy and neuropsychiatric complaints, notably paraesthesia. B12 deficiency can affect BOTH CNS and PNS – this is useful diagnostically because there aren’t many diseases that affect BOTH nervous systems. Patients may also have glossitis.
51
What are the signs of Vitamin B12 and folate deficiency?
* SIGNS OF ANAEMIA: pallor, tachycardia
* Signs of the cause: e.g., jaundice in haemolytic anaemia
* VITAMIN B12: peripheral neuropathy, ataxia, subacute combined degeneration of the spinal cord (degeneration of dorsal and lateral columns causing loss of proprioception, ataxia and UMN weakness)
* SEVERE DEFICIENCY OF BOTH: glossitis, angular stomatitis (aka cheilitis), petechiae
52
What are the blood investigations for Vitamin B12 and folate deficiency? Difference between B12, folate and pernicious?
* FBC: high MCV, pancytopenia
* Reticulocyte count: low
* Signs of ineffective erythropoiesis: raised LDH, bilirubin, iron panel, plasma homocysteine
* VITAMIN B12: low B12, normal folate, high methylmalonic acid
* PERNICIOUS: anti-parietal or anti-IF antibody, high serum gastrin (from absence of hydrochloric acid – remember B12 released using peptic acid)
* FOLATE: low folate, normal B12, no antibodies
53
What does a peripheral blood smear show in Vitamin B12 and folate deficiency? (x4)
* Macrocytosis
* Anisocytosis
* Hypersegmented neutrophils (at least 5 lobes): DNA synthesis abnormalities also affect WBCs remember!
* Large metamyelocytes: a precursor for granulocytic white blood cells: eosinophils, neutrophils and basophils, usually found in the bone marrow.
54
What are the other investigations for Vitamin B12 and folate deficiency? (x2)
* Schilling’s test: radiolabelled B12 given orally and IM non-radioactive B12 is given to saturate B12-binding proteins. 24h urine shows low levels of radiolabelled B12 (from poor absorption). This is repeated with oral IF. If radiolabelled B12 is now detected in urine, the cause if likely IF deficiency from pernicious anaemia or gastrectomy. We saturate B12-binding proteins, because B12 is ONLY secreted in the urine when blood is SATURATED.
* Bone marrow biopsy: megaloblasts or myelodysplastic changes
55
How is folate deficiency treated?
Oral folate replacement
56
How is Vitamin B12 deficiency treated? (x3)
* Dietary supplementation
* Cyanocobalamin/hydroxocobalamin IM (synthetic B12) in symptomatic patients
* Treat anaemia with transfusion if severe symptoms, consider with low-dose diuretic if risk of overload
57
How should folate deficiency be managed in relation to Vitamin B12 deficiency?
B12 must be treated first if present as folic acid may worsen neurological complications of untreated B12 deficiency.
58
What are the complications of folate deficiency? (x2)
* NEURAL TUBE DEFECTS IN DEVELOPING FOETUS: these include spina bifida (spinal cord doesn’t develop properly) and anencephaly (absence of a major portion of the brain and skull).
* INCREASED RISK OF THROMBOSIS: this is because without folate, enzymes involved in homocysteine metabolism are deficient, so homocysteine is not metabolised. Very high homocysteine levels are associated with atherosclerosis and premature vascular disease; mildly elevated levels of homocysteine are associated with cardiovascular disease, and probable arterial/venous thrombosis.
59
!!! What are the consequences of B12 deficiency?
NEUROLOGICAL PROBLEMS: these can present in a wide range of ways: B12 deficiency can affect BOTH CNS and PNS – this is useful diagnostically because there aren’t many diseases that affect BOTH nervous systems. So, problems can arise such as bilateral peripheral neuropathy, subacute combine degeneration of the cord (posterior and pyramidal tracts of the spinal cord), dementia, paraesthesia (pins and needles), muscle weakness, difficulty walking, visual impairment, psychiatric disturbance.
60
What is a complication of pernicious anaemia?
Gastric cancer.
61
What is haemolytic anaemia?
Anaemia resulting from haemolysis (breakdown of RBCs), leading to compensatory response from bone marrow, where increased release of reticulocytes occurs.
62
How is haemolytic anaemia classified?
* INHERITED HAEMOLYTIC ANAEMIA: from abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cell.
* AQUIRED HAEMOLYTIC ANAEMIA: from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell.
* INTRAVASCULAR HAEMOLYSIS: occurs if there is very acute damage to the red blood cell.
* EXTRAVASCULAR HAEMOLYSIS: occurs when defective red cells are removed by the spleen or other organ.
* Acquired and inherited can co-exist – extrinsic factors can interact with red cells that have an intrinsic abnormality, meaning exacerbated anaemia. Intravascular and extravascular can also co-exist.
63
What is the aetiology of inherited haemolytic anaemia? (x3)
* Abnormal red cell membrane – hereditary spherocytosis, elliptocytosis
* Abnormal Hb – sickle cell anaemia, thalassemia
* Metabolic abnormalities – pyruvate kinase deficiency, G6PD deficiency.
64
What is the aetiology of acquired haemolytic anaemia? (x6)
* AUTOIMMUNE: AIHA causing damage to red cell membrane, warm or cold antibodies attach to erythrocytes causing haemolysis
* ISOIMMUNE: transfusion reaction
* DRUGS: penicillin, quinine – causes damage to RBC membrane
* INFECTION: malaria, sepsis – causes damage to whole RBC
* TRAUMA: MAHA – caused by red cell fragmentation in abnormal microcirculation
* PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA: acquired RBC membrane defect leading to complement-mediated lysis and subsequent haemolysis
65
What is the aetiology of AIHA?
Usually part of existing autoimmune conditions such as SLE.
66
What is the pathophysiology of AIHA (autoimmune haemolytic anaemia)?
* Autoimmune haemolytic anaemia results from production of antibodies directed at red cell antigens.
* The immunoglobulin bound to the red cell membrane is recognised by splenic macrophages, which remove parts of the red cell membrane leading to spherocytosis.
* Complement components can also be bound to the immunoglobulin molecule, and they are also recognised by receptors on splenic macrophages.
* Spherocytosis also leads to splenic breakdown and removal of RBCs, so it is almost like a positive feedback system.
67
What is the pathophysiology of MAHA?
HUS, DIC, TTP and malignant hypertension damage the endothelial layer of small vessels. As RBCs travel through these damaged vessels, they become fragmented (schistocytes) resulting in intravascular haemolysis.
68
What is the pathophysiology of hereditary spherocytosis?
Autosomal dominant condition where a structural membrane protein called spectrin is low. As such, the cells lose membrane in the spleen and thus become spherocytic. RBCs become inflexible and rigid because of their spherical shape. They are therefore removed and broken down prematurely by the spleen.
69
What is the pathophysiology of G6PD deficiency?
* X-linked recessive (inherited) • G6PD is important in maintaining glutathione in reduced state • Deficiency results in susceptibility to oxidative stress, precipitated by certain drugs such as sulphonamides and nitrofurantoin (acquired)
* This leads to irregularly contracted cells and Hb denaturation, producing Heinz bodies (Hb condenses and forms around inclusions)
* These are removed from the circulation by the spleen (extravascular), or left with a defect from the spleen
* There is also intravascular haemolysis
70
What are warm and cold antibodies in relation to haemolytic anaemia?
‘Warm’ antibodies (IgG) agglutinate erythrocytes at 37 ̊C. Associated with SLE, lymphomas or methyldopa. ‘Cold’ antibodies (IgM) agglutinate erythrocytes in at room temperature or colder. Associated with infections (e.g., Mycoplasma, EBV) or lymphomas.
71
What is the epidemiology of haemolytic anaemia: Where?
Mediterranean, Middle East, Sub-Saharan Africa, or Southeast Asia
72
What are the symptoms and signs of haemolytic anaemia?
* Pallor, fatigue, SOB (anaemia)
* Jaundice (increased bilirubin from haemolysis)
* Splenomegaly
* Episodic haemoglobinuria (dark urine) suggestive of paroxysmal nocturnal haemoglobinuria
73
What are the investigations for haemolytic anaemia? (x6)
* FBC: raised MCHC (from spherocytes etc.), normal/raised MCV
* Raised reticulocytes – bone marrow response to anaemia
* Unconjugated bilirubin
* Low haptoglobin (suggestive of increased plasma Hb from haemolysis)
* High LDH
* Coomb’s test: detects presence of antibodies to RBCs
74
Why is LDH a good marker in haematology?
RBCs contain lots of LDH, so high levels of free LDH in the blood may indicate haemolysis.
75
What does a peripheral blood smear show in haemolytic anaemia?
Leucoerythroblastic picture: macrocytosis, reticulocytes, polychromasia. Can also identify spherocytes, elliptocytes, schistocytes, sickle cells, malarial parasites, Heinz bodies.
76
When should haemolytic anaemia be suspected? (x4)
* Otherwise unexplained anaemia which is normochromic and usually either normocytic OR macrocytic.
* Evidence of morphologically abnormal red blood cells e.g. spherocytes, elliptocytes, sickle cells, fragmented cells (MAHA).
* Evidence of increased red blood cell breakdown = increased bilirubin load on liver which could lead to gall stones and jaundice.
* Evidence of increased bone marrow activity, specifically a high reticulocyte count.
77
What is aplastic anaemia?
Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopenia).
78
What is the aetiology of aplastic anaemia? (x3 (x5, x2))
* IDIOPATHIC (most common): from destruction or suppression of the stem cell by autoimmune mechanisms
* ACQUIRED: drugs (chloramphenicol, gold, alkylating agents, antiepileptics), chemicals (DDT, benzene), radiation, viral infection (B19 parvovirus, HIV, EBV), paroxysmal haemoglobinuria
* INHERITED: Fanconi’s anaemia, dyskeratosis congenita (associated with reticulated hyperpigmented rash, nail dystrophy and mucosa leucoplakia – white patch in mouth).
79
What is Fanconi’s anaemia? Characterised by? (x7)
Rare autosomal recessive or X-linked disorder caused by an error of DNA repair. Characterised by familial aplastic anaemia, short stature, abnormality of thumbs, café-au-lait spot (coffee-coloured macula), microcephaly, hypogonadism and renal tract defects.
80
What is the pathophysiology of dyskeratosis congenita? Characterised by? (x3)
X-linked characterised by the triad of abnormal nails, reticulated skin rash, and leucoplakia. Autosomal patterns also observed. The genetic defects all decrease telomerase function. Telomeres maintain chromosomal stability, and the bone marrow is heavily dependent on telomere preservation to support its high rate of cell proliferation. Loss of telomerase produces bone marrow failure.
81
What is the epidemiology of aplastic anaemia: Age? Gender?
Can occur at any age. Slightly more common in males.
82
What are the symptoms and signs of aplastic anaemia? (x3) Onset?
* CAN BE SLOW (months) OR RAPID (days) ONSET
* ANAEMIA: tiredness, lethargy, dyspnoea, pale
* THROMBOCYTOPENIA: bleeding gums, epistaxis, petechiae, bruises
* LEUKOPENIA: increased frequency and severity of bacterial and fungal infections WITHOUT hepatosplenomegaly or lymphadenopathy
83
What are the investigations for aplastic anaemia? (x3)
* BLOOD: low Hb, platelets, WCC. Low or absent reticulocytes. Normal MCV
* BLOOD FILM: exclude leukaemia
* BONE MARROW TREPHINE BIOPSY: for diagnosis: should show hypocellularity without evidence of significant dysplasia, blasts, fibrosis or other abnormal infiltrate
84
What is the criteria for severe aplastic anaemia? (x2)
Marrow showing less than 25% of normal cellularity, OR marrow showing less than 50% of normal cellularity, less than 30% of the cells are haematopoietic AND two of the following: low neutrophils, platelets and reticulocytes.
85
How is Fanconi’s anaemia diagnosed?
Presence of increased chromosomal breakage in lymphocytes cultured in the presence of DNA cross-linking agents
