1. Anaemia Flashcards
What is anaemia ?
Low haemaglobin concentration
Adult Male 130 - 180 g/l
Adult Female 115 - 165 g/l
What does Haemaglobin (Hb) tell you? ranges?
Adult Male 130 - 180 g/l
Adult Female 115 - 165 g/l
Amount of haemoglobin in whole blood
low - Anaemia
high - Polycythaemia
History taking anaemia
Anaemia symptoms and complications: fatigue, tiredness, exercise intolerance, SOB, palpitations, oedema, pins and needles, weakness
Microcytic: blood loss - menorrhagia, harmaturia, change in bowel habit, surgery
Normocytic: bone pain, night sweats, weight loss, easy bruising, jaundice, itching
Macrocytic: cold intolerance, abdo distension
MHx chronic diseases, kidney problems, hypertension, liver problems, t1dm
DHx: methotrexate, alcohol, IDA risk drugs (use of aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, clopidogrel, corticosteroids, and long-term proton pump inhibitors)
FHx blood disorders, anyone require blood transfusion? Liver disease?
SHx : diet, recent travel
symptoms of anaemia?
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions, such as angina, heart failure or peripheral arterial disease
IDA
Pica (dietary cravings for abnormal things, such as dirt or soil)
Examination anaemia?
General inspection
- Hair loss
- Dry and rough skin, dry and damaged hair.
- Angular cheilosis (ulceration of the corners of the mouth).
- Atrophic glossitis.
- Nail changes, such as longitudinal ridging and koilonychia (spoon-shaped nails).
Abdominal examination
- peripheral signs of anaemia (pallor, dry skin, brittle hair, koilynycia, longitudinal ridging)
- ?bleed
- hepatosplenomegaly (extramedullary production)
Cardiac examination
- heart failure
- murmurs
- tachycardia
Neuro
- sensation and motor
Skin/mouth changes iron deficiency anameia
Dry and rough skin
Angular cheilosis (ulceration of the corners of the mouth).
Atrophic glossitis.
Nail changes iron defieceny anaemia
longitudinal ridging
koilonychia (spoon-shaped nails).
Blood tests for anaemia ?
Effects:
- FBC (Hb and MCV)
- Reticulocyte count
Microcytic
- iron studies (total iron, ferritin, TIBC)
- peripheral blood film
- Hb electrophoresis
- Blood film
- renal profile
- LFTs and bilirubin
- coeliac disease serology (anti-ttg)
Normocytic
- direct coombs test
- serum protein electrophoresis
Macrocytic
- B12, folate
- intrinsic factor antibodies
- thyroid function tests
what does reticulocyte tell you?
number of reticulocytes (immature RBCs) normal is 0.2-2%
Raised reticulocyte in presence of anaemia = bone marrow working to correct the anaemia. This would therefore suggest red blood cells are being destroyed in the peripheral circulation (e.g. haemolysis, bleeding) rather than there being an issue with the production of red blood cells in the bone marrow itself.
Low reticulocyte count in the context of anaemia implies a problem with the bone marrow not being able to make enough cells. This could be due to nutritional deficiencies (e.g. B12/folate or iron) or a primary bone marrow disorder (e.g. aplastic anaemia, bone marrow infiltration from solid organ malignancies).
A raised reticulocyte count in the absence of anaemia may indicate that the body is effectively compensating for blood loss or haemolysis (i.e. the increased production is managing to replenish the number of cells being lost in the peripheral circulation). Alternatively, a raised reticulocyte count in the absence of anaemia may be due to the body adapting to increased oxygen demands.
what does red cell distribution tell you?
looks at range of sizes of RBC
Useful where there is a false normocytic MCV due to mix of micro and macro eg in iron, B12 and folate deficiency in coeliac disease
Causes of microcytic anaemia
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
Causes of normocytic anaemia
There are 3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
Causes of macrocytic anaemia
Megaloblastic anaemia is caused by:
B12 deficiency
Folate deficiency
Normoblastic macrocytic anaemia is caused by:
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
Approach to microcytic anaemia
- Iron study
- Fe, ferritin low. TIBC high = iron deficiency anaemia
- Fe and TIBC are low but ferritin is high = anaemia of chronic disease
- Fe high, ferritin high, TIBC low
- Iron study normal = ?thalassemia - Blood smear
basophilic stippling and ringed sideroblasts = sideroblastic anaemia - Hb electrophoresis
Increased HbA2 = beta thalassemia
HbH=Hb H disease (alpha thalassemia)
if youre measuring ferritin, what other test should you do?
CRP
it is an acute inflamamtory phase substance so will increase in inflammation (false normal result)
Causes of iron defieicny anaemia
Poor iron intake
Phytate (found in wholegrain cereals, nuts, seeds and legumes), polyphenols (found in tea and coffee) and calcium (in dairy products) impair iron absorption.
Failure of absorption: surgery, coeliac
Drugs (use of aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, clopidogrel, corticosteroids, and long-term proton pump inhibitors) Tetracyclines and quinolones chelate with iron so that neither the antibiotic nor the iron is absorbed.
Bleeding
Excessive requirement of iron: growth in children, pregnancy,
when should you refer patients with IDA
IDA 60+ = 2ww colorectal
IDA <60 = offer FIT test first
IDA <50 with rectal bleeding = 2ww colorectal
IDA women 55+ with haematuria = direct access USS endometrial
IDA 55+ with upper abdo pain = non-urgent direct access endoscopy - upper GI ca
All men and postmenopausal women with iron deficiency anaemia unless they have overt non-gastrointestinal bleeding = refer to gastro
any symptoms of specific cancers - refer to referral criteria
Management of iron defieicny anaemia
- see if any referral needed quickly eg 2ww
- FIT testing
- Address any underlying causes that can be managed in primary care (for example treat menorrhagia or stop nonsteroidal anti-inflammatory drugs, if possible).
+ 65 mg elemental iron (ferrous sulfate 200 mg) once daily (on an empty stomach)
+ advise the person to maintain an adequate balanced intake of iron-rich foods (for example dark green vegetables, iron-fortified bread, meat, apricots, prunes, and raisins) and consider referral to a dietitian
What are the main causes of bleeding leading to IDA
Malignancy: colon, oesophageal/stomach, endometrial
Menorrhagia: endometrial ca^, fibroids, dysfunctional uterine bleeding, hypothyroid, (see other topics)
Major trauma/surgery
main adverse effects iron supplements? what to do in that cirucmstance?
gastrointestinal disturbance
For people with significant intolerance to oral iron replacement therapy options include alternate day dosing, oral ferric maltol, or parenteral iron preparations.
Presentation of colorectal cancer
PC: change in bowel habit, rectal bleeding/melena, abdominal pain/cramping/discomfort, unexplained weight loss, anaemia, bowel obstruction
2ww criteria colorectal cancer
Refer adults using a suspected cancer pathway referral (for an appointment within 2 weeks) for colorectal cancer if:
they are aged 40 and over with unexplained weight loss and abdominal pain or
they are aged 50 and over with unexplained rectal bleeding or
they are aged 60 and over with:
iron‑deficiency anaemia or
changes in their bowel habit, or
tests show occult blood in their faeces.
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for colorectal cancer in adults with a rectal or abdominal mass.
Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for colorectal cancer in adults aged under 50 with rectal bleeding and any of the following unexplained symptoms or findings:
abdominal pain
change in bowel habit
weight loss
iron‑deficiency anaemia.
when are FIT tests used
FIT tests can be used as a test in general practice to help assess for bowel cancer in specific patients who do not meet the criteria for a two week wait referral, for example:
Over 50 with unexplained weight loss and no other symptoms
Under 60 with a change in bowel habit
FIT test screening program
screening every 2 years to all men and women aged 60 to 74 years. Patients aged over 74 years may request screening.
what do patients with newly diagnosed colorectal cancer need for staging
carcinoembryonic antigen (CEA)
CT of the chest, abdomen and pelvis
gold standard investigation colorectal cancer
Colonoscopy
what classification is used to assess severity of colorectal cancer
TNM classification
T for Tumour:
TX – unable to assess size
T1 – submucosa involvement
T2 – involvement of muscularis propria (muscle layer)
T3 – involvement of the subserosa and serosa (outer layer), but not through the serosa
T4 – spread through the serosa (4a) reaching other tissues or organs (4b)
N for Nodes:
NX – unable to assess nodes
N0 – no nodal spread
N1 – spread to 1-3 nodes
N2 – spread to more than 3 nodes
M for Metastasis:
M0 – no metastasis
M1 – metastasis
Management colorectal cancer
surgical resection
Right hemicolectomy involves removal of the caecum, ascending and proximal transverse colon.
Left hemicolectomy involves removal of the distal transverse and descending colon.
High anterior resection involves removing the sigmoid colon (may be called a sigmoid colectomy).
Low anterior resection involves removing the sigmoid colon and upper rectum but sparing the lower rectum and anus.
Abdomino-perineal resection (APR) involves removing the rectum and anus (plus or minus the sigmoid colon) and suturing over the anus. It leaves the patient with a permanent colostomy.
Hartmann’s procedure is usually an emergency procedure that involves the removal of the rectosigmoid colon and creation of an colostomy. The rectal stump is sutured closed. The colostomy may be permanent or reversed at a later date. Common indications are acute obstruction by a tumour, or significant diverticular disease.
chemo and radiation for rectal
Bevacizumab (anti-VEGF) for mets
What is hartmanns procedure
Hartmann’s procedure is usually an emergency procedure that involves the removal of the rectosigmoid colon and creation of an colostomy. The rectal stump is sutured closed. The colostomy may be permanent or reversed at a later date. Common indications are acute obstruction by a tumour, or significant diverticular disease.
what is low anterior resection syndrome
Low anterior resection syndrome may occur after resection of a portion of bowel from the rectum, with anastomosis between the colon and rectum. It can result in a number of symptoms, including:
Urgency and frequency of bowel movements
Faecal incontinence
Difficulty controlling flatulence
follow up colorectal cancer after curative surgery
3 years
Serum carcinoembryonic antigen (CEA)
CT thorax, abdomen and pelvis
What % of colorectal cancer is related to genes
5%
hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
familial adenomatous polyposis (FAP, <1%)
Screening bowel cancer in lynch’s syndrome
colonoscopy every two years from the age of 25 until the number of polyps make prophylactic colectomy advisable. Upper gastrointestinal (GI) endoscopy every two years from the age of 50.
Presentation endometrial cancer
post-menopausal bleeding is the classic symptom
pre-menopausal women may have a change intermenstrual bleeding
haematuria
pain and discharge are unusual features
Risk factors endometrial cancer
obesity
nulliparity
early menarche
late menopause
unopposed oestrogen. The addition of a progestogen to oestrogen reduces this risk (e.g. In HRT). The BNF states that the additional risk is eliminated if a progestogen is given continuously
diabetes mellitus
tamoxifen
polycystic ovarian syndrome
Invetsigations endometrial cancer
first-line investigation is trans-vaginal ultrasound - a normal endometrial thickness (< 4 mm) has a high negative predictive value
hysteroscopy with endometrial biopsy
Management endometrial cancer
localised disease is treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy. Patients with high-risk disease may have post-operative radiotherapy
progestogen therapy is sometimes used in frail elderly women not consider suitable for surgery
Referral criteria upper GI malignancy
- Immediate endoscopy if evidence eg GI bleed (melena, coffee ground vomit)
2ww urgent direct access upper GI endoscopy if:
- dysphagia
- aged 55 and over with weight loss and any of the following:
- upper abdominal pain
- reflux
- dyspepsia.
Consider non‑urgent direct access upper GI endoscopy if:
- haematemesis
Consider non‑urgent direct access upper gastrointestinal endoscopy to assess for stomach cancer in people aged 55 or over with:
- treatment‑resistant dyspepsia
- upper abdominal pain with low haemoglobin levels
- raised platelet count with any of the following:
nausea
vomiting
weight loss
reflux
dyspepsia
upper abdominal pain
- nausea or vomiting with any of the following:
weight loss
reflux
dyspepsia
upper abdominal pain.
Most common type of oesophageal cancer UK
adenocarcinoma which is present in lower ⅓ of oesophagus,
in other parts of the world, squamous cell carcinoma is most common, present in upper ⅔ of oesophagus.
Presentation oesophageal cancer
PC: dysphagia: the most common presenting symptom, anorexia and weight loss, vomiting, odynophagia, hoarseness, melaena, cough
MHx: GORD, barretts oesophagus, obesity (if adenocarcinoma)
DHx
FHx
SHx: smoking, alcohol
Plan oesophageal cancer
Investigation:
Upper GI endoscopy with biopsy for diagnosis
CT and endoscopy USS used for staging
Management:
surgical management if operbale - Ivor-Lewis type oesophagectomy
adjuvant chemotherapy
Priamry risk factor for gastric cancer
Helicobacter pylori infection is the primary risk factor for gastric cancer, accounting for approximately 75% of cases
Persistent infection with H. pylori can induce chronic inflammation, leading to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually, gastric adenocarcinoma.
Risk factors gastric cancer
PRIAMRY - h.pylori
Additional:
Dietary factors: High salt intake, consumption of smoked or preserved foods, and low intake of fruits and vegetables
Smoking
Alcohol consumption
Pernicious anaemia and atrophic gastritis
Family history of gastric cancer
Genetic syndromes (e.g., hereditary diffuse gastric cancer, Lynch syndrome)
Presentation gastric cancer
PC:
Symptoms of gastric cancer are often nonspecific, especially in the early stages. Common clinical features include:
Dyspepsia or indigestion
Epigastric pain
Early satiety or postprandial fullness
Weight loss
Anaemia
Nausea and vomiting
Gastrointestinal bleeding (e.g., melena, haematemesis)
Advanced disease may present with additional signs, such as palpable abdominal mass, ascites, and supraclavicular lymphadenopathy (Virchow’s node).
Examination findings gastric cancer
Advanced disease may present with additional signs, such as palpable abdominal mass, ascites, and supraclavicular lymphadenopathy (Virchow’s node).
Platelet count cancer
High
Cancer is believed to induce platelet formation through the release of interleukin 6, a proinflammatory cytokine that stimulates the production of thrombopoietin hormone.
Investigations gastric cancer
diagnosis: endoscopy with biopsy
staging: CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be superior to CT
CT scanning of the chest abdomen and pelvis is the routine first line staging investigation in most centres.
Laparoscopy to identify occult peritoneal disease
PET CT (particularly for junctional tumours)
Management gastric cancer
Chemo
Radiation
Surgery
Pathophysiology anaemia of chronic disease
Occurs in patients with chronic infections and inflammatory disease
TB, chrons, RA, SLE, malignancy
Inflammation → release of cytokines → release of hepicidin → anaemia
Hepcidin:
Inhibits intestinal iron absorption
Inhibits iron release from iron stores
Inhibits EPO sensitivity
Reduces erythrocyte lifespan
MCV anaemia of chronic disease
FBC - normocytic anaemia then microcytic as iron is depleted
Iron studies iron deficiency anaemia
Fe low
Ferritin low
TIBC high
Transferrin saturations low
Iron studies anameia of chronic disease
Fe low
Ferritin high (stored iron cant be utilised)
TIBC low (stored iron cant be utilised)
Transferrin saturations low
management anaemia of chronic disease
Don’t respond to iron therapy
Treat underlying disorder
Causes of sideroblastic anaemia
Inherited
gene defect
Acquired
alcohol excess
lead poisoning
Copper deficiency
B6 deficiency
Drugs
Myelodysplasia / AML
features of lead poisoning
Abdominal pain, peripheral neuropathy motor, blue lines on gum margin
Pathophysiology sideroblastic anaemia
Immature RBC - constellation of iron as there is a defect in protoporphyrin synthesis → cant form heme → Iron trapped within cell (in mitochondria)
Iron built up → organ damage eg damage to kidneys, liver, spleen, heart etc
Iron studies sideroblastic anaemia
Fe high
Ferritin high
TIBC low
Transferrin saturations high
Investigations sideroblastic anaemia
Low RBC, low haemoglobin, low hematocrit
Serum iron high
Ferritin high
TIBC low
Transferrin saturations high
Peripheral blood smear = basophilic stippling
Bone marrow biopsy = ringed sideroblasts
Examination finding siderobalastic anaemia
Hepatosplenomegaly is found in a third to a half of people with sideroblastic anaemia and is not present in iron deficiency anaemia.
Management of siderobalstic anaemia
Stop offending agent
Pyridoxine (B6) supplement - cofactor in gene pathway
Inheritance thalassemia
autosomal recessive
Pathophysiology thalassemia
genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta-globin chains.
Defects in alpha-globin chains leads to alpha thalassaemia. Defects in the beta-globin chains leads to beta thalassaemia.
In thalassaemia, the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in splenomegaly.
The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences (cheekbones).
Signs and symptoms thalassemia and pathophysiology of symptoms
Microcytic anaemia (low mean corpuscular volume) (less stuff in the RBC)
Fatigue (anaemia)
Pallor (anaemia)
Jaundice (quicker breakdown)
Gallstones (higher bilirubin due to RBC breakdown –> ppt gallstones)
Splenomegaly (swelling due to increased use - removing old RBC)
Hepatomegaly related to significant extramedullary hematopoiesis
Poor growth and development (anaemia?)
Pronounced forehead and malar eminences (extramedullary production of RBC)
Invetsigations thalassemia
Full blood count shows a microcytic anaemia.
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
DNA testing can be used to look for the genetic abnormality
Pregnant women in the UK are offered a screening test for thalassemia at booking.
Why does iron overload occur in thalassemia? symptoms?
Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
Iron overload in thalassaemia causes effects similar to haemochromatosis:
Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
why do you need to check ferritin thalassemia patients
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation.
what chromosome is genes alpha thalassemia
chromosome 16
Alpha thalassemia genes explanation and results
Gene HBA1 and HBA2
So 4 alleles in each parent
Pass on 2 each to child
either present or deleted
In child:
number of missing alleles
1 missing - silent carrier
2 misisng - alpha thalssemia trait
3 missing - HbH disease
4 missing - Hb Bart’s - hydrops fetalis
what is alpha thalssemia trait
2 alleles missing - minor anaemia
What is HbH disease? how is patient affected?
3 missing alleles - alpha thalssemia
mild to moderate haemolytic anaemia, which may or may not require medical intervention. Cases can be severe – usually during an acute illness or increased metabolic exacerbation, such as during pregnancy.
What is Hb Barts disease?
4 missing alleles alpha thalassemia
incompatible with life
usually die in utero
hydrops fetalis
ethnicity risk alpha thalssemia
Southeast Asia, the Middle East, China, and in those of African descent.
What chromosome beta thalassemia
chromosome 11
Beta thalassmeia gene and explanation inheritance
HBB gene chromosome 11
Both parents have 2 alleles
Pass on 1 each
Gene either fucntional, partially functional (+), or no fucntion (0)
B0/B0 - beta thalassemia major - severe symptomatic anaemia age 2
B+/B+ or B+/B0 - beta thalassemia intermedia - symptomatic later in life moderate
B/B+ or B/B0 - beta thalassemia minor/trait - asymptomatic/mild
Presentation beta thalassemia major
present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, prenatal screening is very important.
transfusiond ependent
Presentation beta thalssemia intermedia
Those with beta thalassemia intermedia (those who are compound heterozygotes for the beta thalassemia mutation) usually present later in life with mild to moderate symptoms of anemia
PResentation beta thalssemia minor/trait
Beta thalassemia trait (also known as beta thalassemia minor) involves heterozygous inheritance of a beta-thalassemia mutation and patients usually have borderline microcytic, hypochromic anemia and they are usually asymptomatic or have mild symptoms.
ethnicity beta thalssemia
Beta thalassemia most often occurs in people of Mediterranean origin. To a lesser extent, Chinese, other Asians, and African Americans can be affected.
Management thalassemia
Depending on the type/severity, there are different treatment requirements and options including:
Monitoring the full blood count
Monitoring for complications
Blood transfusions
Iron chelation- desferrioxamine
Splenectomy may be performed
Bone marrow transplant can be curative
which thalassemia is usually transfusiond ependent
beta major
microscopy megaloblastic anaemia
hypersegmented neutrophils - (more than 5 lobes)
Approach to macrocytic anaemia
- Check folate and B12 levels
- If normal : non megaloblastic causes (liver disease, alcohol, hypothyroid, reticulocytosis)
pathophysiology megalobastic anaemia
Megaloblastic anaemia results from impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.
most common cause megaloblastic anaemia
Pernicious anaemia accounts for 80% of cases of megaloblastic anaemia due to impaired absorption of vitamin B12.
vitamin b12 defienct values? what other invetsigations support?
Deficiency is likely: <148 picomole/L
Deficiency is probable: 148 to 258 picomole/L
Deficiency is unlikely: >258 picomole/L
Methylmalonic acid (MMA) and homocysteine (Hcy) level - both usually elevated with low B12- supports diagnosis
Presentation b12 defieciency
Haematological: anaemia and associated symptoms
Neurological: subacute combined degeneration of the spinal cord (SACD) - bilateral dorsal column signs, may have bilateral corticospinal tract signs (affects posterior cord)
and sensory loss peripheral neuropathy
Psychiatric: mild neurosis to severe dementia; depression, personality change, psychosis, bipolar disorder, panic disorder and phobia
presentation subacute degeneration of spinal cord
bilateral dorsal column signs, may have bilateral corticospinal tract signs (affects posterior cord)
prevention subacute combined degeneration of spinal cord
Always replace vitamin B12 before folate - giving folate to a patient deficient in B12 can precipitate subacute combined degeneration of the cord
causes b12 deficiency
Malabsorption, e.g. Pernicious anaemia, Helicobacter pylori infection, atrophic gastritis
Inadequate intake, e.g. vegan or vegetarian diet
Increase in requirement, e.g. pregnancy, hyperthyroidism
Drug induced (OCP)
Congenital, e.g. cobalamin transport disorder
investigations pernicious anaemia
Anti-intrinsic factor antibodies for pernicious anaemia
Anti-parietal cell antibodies (to confirm/refute if anti-intrinsic antibodies negative)
what are people with pernicious anaemia at increased risk of?
gastric cancer
management b12 deficieny
With neurological involvement
Replacement therapy:
- IM hydroxocobalamin 1mg once daily on alternative days until no further improvement
Maintenance therapy:
- IM Hydroxocobalamin 1mg, which usually lasts for life, once every 2 months
Without neurological involvement
Replacement therapy:
- IM Hydroxocobalamin 1mg three times a week for 2 weeks
Maintenance therapy (diet related):
- IM Hydroxocobalamin 1mg twice a year
Maintenance therapy (non-diet related):
- IM Hydroxocobalamin 1mg once every 2-3 months for life
Within 7 to 10 days of starting treatment, FBC should be performed to check for treatment response.
No response: check serum folate level
Haemoglobin level and reticulocyte index above normal range: adequate treatment
other name for b12
cobalamin
causes folate deficiency
Folate deficiency is often caused by problems with dietary intake alone, or in a combination with increased folate usage, or malabsorption. For example:
Drugs — alcohol, anticonvulsants, nitrofurantoin, sulfasalazine, methotrexate, trimethoprim.
Excessive requirements in pregnancy, malignancy, blood disorders, or malabsorption.
Excessive urinary excretion.
Liver disease.
management folate deficiency
Prescribe oral folic acid 5 mg daily — in most people, treatment will be required for 4 months.
However, folic acid may need to be taken for longer (sometimes for life) if the underlying cause of deficiency is persistent.
what do you need to check before giving folate
Check vitamin B12 levels in all people before starting folic acid
ALWAYS CORRECT B12 BEFORE FOLATE
Presentation coeliac disease
Coeliac disease is often asymptomatic, so have a low threshold for testing for coeliac disease in patients where it is suspected. Symptoms can include:
Failure to thrive in young children
Features may coincide with the introduction of cereals (i.e. gluten)
Diarrhoea
Fatigue
Weight loss
Mouth ulcers
Anaemia secondary to iron, B12 or folate deficiency
Dermatitis herpetiformis is an itchy blistering skin rash that typically appears on the abdomen
Rarely coeliac disease can present with neurological symptoms:
Peripheral neuropathy
Cerebellar ataxia
Epilepsy
genetic associations coeliac
HLA-DQ2 gene (90%)
HLA-DQ8 gene
auto-antibodies coeliac
Tissue transglutaminase antibodies (anti-TTG)
Endomysial antibodies (EMAs)
when testing for auto-antibodies, what else do you need to test for
total IgA
When you test for these antibodies, it is important to test for total Immunoglobulin A levels because if total IgA is low the coeliac test will be negative even when they have the condition. In this circumstance you can test for the IgG version of the anti-TTG or anti-EMA antibodies or do an endoscopy with biopsies.
what will endoscopy biposy show coeliac disease
“Crypt hypertrophy”
“Villous atrophy”
where in SI should bipsy be taken from coeliac
duodenum classically. jejunum most affected
Investigations coeliac
- auto-antibody testing
Tissue transglutaminase antibodies (anti-TTG)
Endomysial antibodies (EMAs) - If positive –>
Arrange referral for young people and adults to a gastroenterologist for specialist endoscopic intestinal biopsy to confirm or exclude the diagnosis.
Arrange referral for children to a paediatric gastroenterologist for further investigation to confirm or exclude the diagnosis. This may include further serology testing, intestinal biopsy, human leukocyte antigen (HLA) genetic testing, or a combination of these.
associations coeliac
Type 1 diabetes
Thyroid disease
Autoimmune hepatitis
Primary biliary cirrhosis
Primary sclerosing cholangitis
Down’s syndrome
complications untreated coeliac
Vitamin deficiency
Anaemia
Osteoporosis
Ulcerative jejunitis
Enteropathy-associated T-cell lymphoma (EATL) of the intestine
Non-Hodgkin lymphoma (NHL)
Small bowel adenocarcinoma (rare)
anaemia alcohol
Macrocytic
1. Folate deficiency
chronic alcohol exposure impairs folate absorption by inhibiting expression of the reduced folate carrier and decreasing the hepatic uptake and renal conservation of circulating folate.
heavy alcohol consumption can cause generalized suppression of blood cell production and the production of structurally abnormal blood cell precursors that cannot mature into functional cells. Alcoholics frequently have defective red blood cells that are destroyed prematurely, possibly resulting in anemia.
In many alcoholic patients, blood loss and subsequent iron deficiency are caused by gastrointestinal bleeding.
How does hypothyroid cause anaemia
The low thyroid hormone levels of hypothyroidism suppress the activity of bone marrow, the tissue that makes red blood cells.
TFTs hypothyroid
TSH is raised, and T3 and T4 are low
autoantibodies hashimotos
anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies
What drugs can ppt hypothyroid
Lithium inhibits the production of thyroid hormones in the thyroid gland and can cause a goitre and hypothyroidism.
Amiodarone interferes with thyroid hormone production and metabolism, usually causing hypothyroidism but can also cause thyrotoxicosis.
presentation hypothyroid
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (including oedema, pleural effusions and ascites)
Heavy or irregular periods
Constipation
causes secondary hypothyroid
Secondary hypothyroidism is often associated with a lack of other pituitary hormones, such as ACTH, referred to as hypopituitarism. This is rarer than primary hypothyroidism, and may be caused by:
Tumours (e.g., pituitary adenomas)
Surgery to the pituitary
Radiotherapy
Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
Trauma
examination hashimotos
Hashimoto’s thyroiditis can initially cause a goitre, after which there is atrophy (wasting) of the thyroid gland.
management hypothyroid
Oral levothyroxine is the mainstay of treatment of hypothyroidism. Levothyroxine is a synthetic version of T4 and metabolises to T3 in the body.
The dose is titrated based on the TSH level, initially every 4 weeks.
How does liver disease cause anaemia
Microcytic:IDA due to acute or chronic blood loss into the gastrointestinal tract. Anemia of chronic disease
Normocytic: early stages of anaemia of chronic disease
Macrocytic : lipid deposition on RBC membranes making them bigger
Causes normocytic anaemia
Haemolytic: RBC are normal but are being destroyed
Non-haemolytic: RBC are either being lost or not being made by BM
There are 3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of chronic disease and chronic kidney disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
causes haemolytic anaemia
Rhesus - haemolytic anaemia of the newborn
Hereditary spherocytosis
G6PD deficiency
Sickle cell disease
Autoimmune haemolytic anaemia
ttp
Extrinsic causes : eg malaria, clostridium, burns, mediations, prosthetic heart valves
why is rhesus status important? what does it mean?
The rhesus D antigen is found on RBC.
If someone who is rhesus negative, comes into contact with the rhesus antigen - it sees this as foreign and creates antibodies.
It is important to pick up rhesus-D negative mothers as they may have rhesus positive babies
If the baby’s blood comes into contact with the mothers blood then the mother will produce antibodies against the babies blood (sensitisation)
In future pregnancies, the mothers immune system may initiate a full scale attack and destroy the babies RBC.
Once sensitisation has occurred, there is nothing that can be done. therefore prophylaxis is important to prevent sensitisation
How does anti-D work?
The anti-D medication works by attaching itself to the rhesus-D antigens on the fetal red blood cells in the mothers circulation, causing them to be destroyed. This prevents the mother’s immune system recognising the antigen and creating it’s own antibodies to the antigen. It acts as a prevention for the mother becoming sensitised to the rhesus-D antigen.
When is anti-D given?
Anti-D injections are given routinely on two occasions:
- 28 weeks gestation
- Birth (if the baby’s blood group is found to be rhesus-positive)
Anti-D injections should also be given at any time where sensitisation may occur
Anti-D is given within 72 hours of a sensitisation event. If a sensitisation test occurs after 20 weeks gestation, the Kleinhauer test is performed to see how much fetal blood has passed into the mother’s blood, to determine whether further doses of anti-D are required.
In what situations should an anti-D be given within 72 hours
delivery of a Rh +ve infant, whether live or stillborn
any termination of pregnancy
miscarriage if gestation is > 12 weeks
ectopic pregnancy if managed surgically
external cephalic version
antepartum haemorrhage
amniocentesis, chorionic villus sampling, fetal blood sampling
abdominal trauma
Tests for rhesus sensitisation ?
all babies born to Rh -ve mother should have cord blood taken at delivery for FBC, blood group & direct Coombs test
Coombs test: direct antiglobulin, will demonstrate antibodies on RBCs of baby
Kleihauer test: add acid to maternal blood, fetal cells are resistant (do after a sensitisation event to see if further foses of anti-d are required)
How will an affected fetus present - rhesus sensitisation? pathophysiology? tretament?
jaundice –> kerinicterus, anaemia, hepatosplenomegaly:
anaemia is caused by the destruction of the RBC by the mothers antibodies, jaundice occurs as there is lots of bilirubin from the breakdown of RBC. The spleen is enlarged as it is processing a lrge number of RBC. the liver is large as it is trying to make much more RBC than normal.
oedema and hydrops fetalis:
liver is under strain from making more RBC that other functions suffer such as albumin production. this leads to leakage of fluid into tissues and body cavities, termed hydrops fetalis.
heart failure:
liver is under strain so portal hypertension devlops which strains the heart and ciruclatory system. Also, the severe anemia taxes the heart to compensate by increasing output in an effort to deliver oxygen to the tissues and results in a condition called high output cardiac failure.
treatment: transfusions, UV phototherapy
why does rhesus only cause outcomes in subsequent pregnancies and not the first?
IgM antibodies do not cross the placental barrier, which is why no effects to the fetus are seen in first pregnancies for Rh-D mediated disease.
However, in subsequent pregnancies with Rh+ fetuses, the IgG memory B cells mount an immune response when re-exposed, and these IgG anti-Rh(D) antibodies do cross the placenta and enter fetal circulation.
pathophysiology g6pd
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
G6PD deficiency renders RBCs susceptible to oxidative stress, which shortens RBC survival. Hemolysis occurs following an oxidative challenge, commonly after fever, acute viral or bacterial infections, and diabetic ketoacidosis.
Presentation G6PD and spherocytosis
acute episodes of haemolysis
neonatal jaundice
gallstones
splenomegaly
failure to thrive
inheritance g6pd
X-linked
grandpa- dad
blood film g6pd
Heinz bodies on blood films. Bite and blister cells may also be seen
diagnosis g6pd
Diagnosis is made by using a G6PD enzyme assay
levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results
things that may precipitate a crisis g6pd
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
acute illness
DKA
fava (broad) beans
ethnicity RF g6pd
Mediterranean and Africa
ethnicity spherocytosis
northern European descent
inheritance spherocytosis
autosomal diminant
diagnosis spherocytosis
- if family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
- EMA binding test and the cryohaemolysis test
- for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice
Pathophysiology spherocytosis
defect of red blood cell cytoskeleton
the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
red blood cell survival reduced as destroyed by the spleen
management spherocytosis acute adn chronic
acute haemolytic crisis:
treatment is generally supportive
transfusion if necessary
longer term treatment:
folate replacement
splenectomy
neonatal jaundice <24 hours, plan?
<24 hours PATHOLOGICAL - check bilirubin level and do peripheral blood smear
Pathophysiology sickle cell
Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS causes red blood cells to be an abnormal “sickle” shape.
sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction
more RBC need to be created to compensate for early destruction
what may precipitate a crisis spherocytosis
parvovirus infection
FBC findings spherocytosis
raised mean corpuscular haemoglobin concentration [MCHC]
increase in reticulocytes
when do symptoms of sickle cell anaemia usually develop
Symptoms in homozygotes don’t tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
inheritance sickle cell
autosomal recessive
HbAA = normal
HbAS = sickle cell trait
HbSS = sickle cell disease
ethnicity sickle cell
Sickle cell disease is more common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean. Having one copy of the gene (sickle-cell trait) reduces the severity of malaria
when is diagnosis of sickle cell made
Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
Sickle cell disease is also tested for on the newborn screening heel prick test at 5 days of age.
Complications of sickle cell
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
General management of sickle cell
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
- Influenza vaccine annually.
- Pneumococcal polysaccharide vaccinePPV23 vaccine every 5 years.
Antibiotic prophylaxis to protect against infection, usually with penicillin V (phenoxymethypenicillin)
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
what does sickle cell crisis mean? causes?
Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening. They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
Blood cells blocking blood flow
Vaso-occlusive crisis (painful crisis) eg priapism and acute chest
Splenic sequestration
Loss of creation of new blood cells
Aplastic crisis
pain management sickle cell crisis
follow care plan
- prescribe paracetamol and/or ibuprofen (avoid ibuprofen if the person has renal impairment or significant proteinuria).
- Weak opioids can be used for more severe pain (dihydrocodeine in children aged under 13 years and codeine phosphate in people aged over 13 years
presentation and manageemnt priapism sickle cell
Obstruction of venous outflow from the corpora cavernosa by sickled cells may cause persistent penile erection accompanied by pain.
This is a urological emergency and is treated with aspiration of blood from the penis.
Pathophysiology acute chest
Acute chest syndrome occurs due to vaso-occlusion within the pulmonary vasculature of patients with sickle cell disease. This results in deoxygenation of hemoglobin and sickling of erythrocytes, which can then cause further vaso-occlusion, ischemia, and endothelial injury.
Acute chest syndrome can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
define acute chest sickle cell
Defined as a new pulmonary infiltrate on the chest radiograph combined with one or more manifestations such as fever, cough, sputum production, tachypnoea, dyspnoea, or new-onset hypoxia.
manageemnt acute chest sickle cell
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
what is splenic sequestration
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to severe anaemia and circulatory collapse (hypovolemic shock).
management splenic sequestraton
Splenic sequestration crisis is considered an emergency. Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction, resulting in susceptibility to infections.
what is an aplastic crisis sickle cell usually caused by? management?
Aplastic crisis describes a situation where there is temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
what infections are people will sickle cell anemia particularly susceptible to
encapsulated bacteria, in particular Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae.
due to reduced fucntion of spleen
Causes of non-haemolytic normocytic anaemia
CKD: low reticulocyte
Blood loss : high reticulocyte
Aplastic anaemia : low reticulocyte
how does CKD cause anaemia? what type
Non-haemolytic normocytic
Kidneys secrete EPO
EPO stimulates RBC production from the bone marrow
In CKD the kidney is damaged and there is decreased production of EPO
This leads to normocytic anaemia as the bone marrow is under stimulated to produce RBC
Patients can receive EPO injections
what does aplastic anaemia mean
Aplastic is a rare condition characterised by pancytopenia and a hypoplastic bone marrow.
blood results aplastic anaemia
need 2 of following:
Haemoglobin concentration below 100 g/L. Normochromic, normocytic
Platelet count below 50 x 109/L.
Neutrophil count below 1.5 x 109/L. with lymphocytes relatively spared
(low reticulocyte count)
presentation aplastic anaemia
Patients with aplastic anaemia most commonly present with symptoms of anaemia (pallor, headache, palpitations, dyspneoa, fatigue, or ankle oedema)
and thrombocytopenia (skin or mucosal haemorrhage, visual disturbance due to retinal haemorrhage, petechial rashes).
Infection - a less common presentation.
There is no lymphadenopathy or hepatosplenomegaly (in the absence of infection).
causes aplastic anaemia
Idiopathic (70-80%)
Congenital: Fanconi anaemia, dyskeratosis congenita
Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Toxins: benzene
Infections: parvovirus, hepatitis → 5-10% of severe acquired cases are preceded by seronegative hepatitis
Radiation
history taking aplastic anameia - thinsg that would point to a specific cause
Children: short stature, café au lait spots and skeletal anomalies suggest the possibility of a congenital form of aplastic anaemia
A family history of cytopenias should raise suspicion of an inherited disorder even when no physical abnormalities are present
A preceding history of jaundice, usually 2-3 months before, may indicate a post-hepatitis aplastic anaemia.
management aplastic anaemia
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
Is highly allergenic and may cause serum sickness (fever, rash, arthralgia), therefore steroid cover usually given
Immunosuppression using agents such as ciclosporin may also be given
Allogeneic transplants have a success rate of up to 80%
inheritance fanconi anaemia
autosomal recessive
what is fanconi anaemia
Fanconi anaemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway.
Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia (the inability to produce blood cells) by age 40.
presentation fanconi anaemia
60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.
management fanconi anaemia
Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available
what cancers do people with fanconi anaemia get
acute myelogenous leukemia (AML), MDS, and liver tumors.
what is leukemia
Leukaemia is the name for cancer of a particular line of the stem cells in the bone marrow. This causes unregulated production of certain types of blood cells. Types of leukaemia can be classified depending on how rapidly they progress (chronic is slow and acute is fast) and the cell line that is affected (myeloid or lymphoid).
what leukemia is the most common in children
acute lymphoblastic leukemia
which leukemia is associated with downs
acute lymphoblastic leukemia
which leukemia is associated with richers transformation and smudge cells
CLL
which leukemia is associated with philedelphia chromosome
CML
which leukenia is assocated with transformation from a myeloproliferative disorder and is associated with auer rods
AML
how does leukemia cuase pancytopenia
Leukaemia is a form of cancer of the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.
The excessive production of a single type of cell can lead to suppression of the other cell lines, causing underproduction of other cell types. This results in a pancytopenia, which is a combination of low:
Red blood cells (anaemia),
White blood cells (leukopenia)
Platelets (thrombocytopenia)
what is required urgently when leukemia is a ddx for a presentation
An urgent full blood count
features of leukemia?
anaemia: lethargy/fatigue and pallor
neutropaenia: frequent or severe infections
thrombocytopenia: easy bruising, petechiae
Hepatosplenomegaly: due to leukemic infiltration
Fever: A persistent, recurrent or refractory fever that is most likely a constitutional symptom and may present alongside a history of night sweats, weight loss.
Lymphadenopathy: a build-up of large numbers of cancerous cells which have travelled from the bone marrow
Failure to thrive (children)
why does leukemia cause hepatosplenomegaly
due to leukemic infiltration
why does leukemia cause lymphadenopathy
a build-up of large numbers of cancerous cells which have travelled from the bone marrow
when should ?leukemia be sent for immediate specialist assessment
They recommend children or young people with petechiae or hepatosplenomegaly are sent for immediate specialist assessment.
initial investigation leukemia
FBC
investigation leukemia
- FBC
- lactate
- bone marrow biopsy
- CT and PET scans
- lymph node biopsy
- genetic tests
what are the two cell lines coming from multipotential hematopoeitic cells
- myeloid –> (megakaryocyte (–> thrombocytes), erythrocyte, mast cells, myeloblast ) then myeloblast –> basophil, neutrophil, eosinophil, monocyte (–> macrophage)
- lymphoid –> natural killer cell and small lymphocyte. small lymphocyte –> T lymphocyte, B lymphocyte (–> plasma cell)
presentation CLL
slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes. It usually affects adults over 60 years of age. It is often asymptomatic but can present with infections, anaemia, bleeding and weight loss. It may cause warm autoimmune haemolytic anaemia.
smudge cellsa ssociated with?
CLL
what is richters transformation
Richter’s transformation refers to the rare transformation of CLL into high-grade B-cell lymphoma.
phases of CML
chronic - years of high WCC
accelerated - blast cells push out other types - anaemia, thrombocytopenia, immunodeficiency
blast phase - over 20% blasts in blood - severe symptoms and is often fatal
CML genetic associtaed
philedelphia chromosome
This refers to an abnormal chromosome 22 caused by a reciprocal translocation (swap) of genetic material between a section of chromosome 9 and chromosome 22.
AML age
from middle age onwards
what may cause AML
myeloprolifertaive disorder such as polycythaemia vera or myelofibrosis
blood film AML
A blood film and bone marrow biopsy will show a high proportion of blast cells. Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.
management leukemia
Leukaemia is mainly treated with chemotherapy and targeted therapies, depending on the type and individual features.
Examples of targleted therapies include (mainly used in CLL):
Tyrosine kinase inhibitors (e.g., ibrutinib)
Monoclonal antibodies (e.g., rituximab, which targets B-cells)
Other treatments options include:
Radiotherapy
Bone marrow transplant
Surgery
complications of chemo
Failure to treat cancer
Stunted growth and development in children
Infections due to immunosuppression
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity (heart damage)
Tumour lysis syndrome
what is tumor lysis syndrome
Tumour lysis syndrome results from chemicals released when cells are destroyed by chemotherapy, resulting in:
High uric acid
High potassium (hyperkalaemia)
High phosphate
Low calcium (as a result of high phosphate)
Uric acid can form crystals in the interstitial space and tubules of the kidneys, causing acute kidney injury. Hyperkalaemia can cause cardiac arrhythmias. The release of cytokines can cause systemic inflammation.
Very good hydration and urine output before chemotherapy is required in patients at risk of tumour lysis syndrome. Allopurinol or rasburicase may be used to suppress the uric acid levels.
what is myelofibrosis
a myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
the resultant release of platelet derived growth factor is thought to stimulate fibroblasts –> fibrosis of bone marrow –> cant do haematopoieis –>
haematopoiesis develops in the liver and spleen
can also be secondary to other myeloprolifertaive diseases
presentation myelofibrosis
e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
invetsigations myelofibrosis
anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
gene test JAK2, MPL and CALR genes can help with diagnosis and management.
what are myeloprolifertaive diseases
a group of neoplastic disorders involving the bone marrow cells that produce RBC, platelts or fibroblasts
- RBC= polycytahemia vera
- platelets = essential thrombocytahemia
- fibrobalsts (triggered by megakaryocytes) - myelofibrosis
management myelofibrosis
Management of primary myelofibrosis may involve:
No active treatment for mild disease with minimal symptoms
Supportive management of complications, such as anaemia, splenomegaly and portal hypertension
Chemotherapy (e.g., hydroxycarbamide) to help control the disease
Targeted therapies, such as JAK2 inhibitors (ruxolitinib)
Allogeneic stem cell transplantation (risky but potentially curative)
what gene mutations is associated with myeloprolifertaive diseases ?
JAK2
MPL
CALR
what type of drug may be used in myeliprolifertaive diseases
JAK2 inhibitors, such as ruxolitinib.
what is myelodysplastic syndorme
Precancerous disease of myeloid cells in bone marrow whereby the dysplastic cells may cause abnormal or inadequate blood cell rpoduction
Badly fucntioning → anaemia, thrombocytopenia, leukopenia etc.
Tries to compensate by increasing haematopoeisis
Dysplasia has risk of progressing to acute myeloid leukemia
FBC myelodysplastic syndrome
Myelodysplastic syndrome causes low levels of blood components that originate from the myeloid cell line:
Anaemia (low haemoglobin)
Neutropenia (low neutrophil count)
Thrombocytopenia (low platelets)
risk factors myelodysplasia
older age and previous chemotherapy or radiotherapy.
presentation myelodysplasia
Patients may be asymptomatic. It may be diagnosed after incidental findings on a full blood count.
They may present with symptoms of:
Anaemia (fatigue, pallor or shortness of breath)
Neutropenia (frequent or severe infections)
Thrombocytopenia (bleeding and purpura)
blood film myelodysplasia
Full blood count will be abnormal. There may be blasts on the blood film.
Bone marrow biopsy is required to confirm the diagnosis.
management myelodyspalsia
Watchful waiting
Supportive treatment (e.g., blood or platelet transfusions)
Erythropoietin (stimulates red blood cell production)
Granulocyte colony-stimulating factor (stimulates neutrophil production)
Chemotherapy and targeted therapies (e.g., lenalidomide)
Allogenic stem cell transplantation (risky but potentially curative)
what are blasts
In the myeloid cell line, the term “blast cell” refers to myeloblasts or myeloid blasts. These are the very earliest and most immature cells of the myeloid cell line.
what is myeloma
Myeloma is a cancer of the plasma cells (type of B lymphocytes that produce antibodies). Cancer in a specific type of plasma cell results in large quantities of a single antibody being produced.
what is Monoclonal gammopathy of undetermined significance (MGUS)
is where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.
pathophysiology myeloma
B cells in bone marrow producing antibodies → genetic mutation causing one antibody to be produced uncontrollably (50% of the time this is IgG)
Bone marrow infiltration → anaemia, neutropaenia, thrombocytopaenia
Plasma cells releasing cytokines → increased osteoclast activity → myeloma bone disease → skull, spine, long bones affected → bone pain / pathological fractures → releasing lots of calcium from bones → hypercalcaemia
Kidney failure is common in patients with a monoclonal gammopathy, most frequently due to hypercalcemia or myeloma cast nephropathy. Immunoglobulin crystallization is an uncommon phenomenon that also results in kidney injury
hypercalcaemia can ppt kidney stones,
presentation myeloma
PC: anaemia
PC: neutropenia
PC: thrombocytopenia
PC: pathological fractures
PC: bone pain, particularly back pain
PC: myeloma renal disease
PC: hyperviscosity
PC: kidney stones
Initial tests myeloma
FBC: anaemia
Calcium and bone profile: hypercalcaemia
U&Es : renal failure
ESR
Plasma viscosity
If suggetsive –>
then very urgent (within 48hrs)
- protein electrophoresis
- bence-jones urine test
if +ve 2ww
bone marrow biopsy and look at all results
diagnostic criteria multiple myeloma
The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.
Major criteria
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
Minor criteria
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
what is a Autologous hematopoietic cell transplantation
involves the removal of a patient’s own stem cells prior to chemotherapy, which are then replaced after chemotherapy
what is allogenic haematopoeitic stem cell transplant
Allogenic hematopoietic cell transplantation
is not commonly used in myeloma due to high rates of overall mortality and symptoms of graft-ve
stages of myeloma treatment
A combination of drugs is used to treat myeloma - ‘induction therapy
targeted drugs (such as thalidomide, lenalidomide, bortezomib, daratumumab)
chemotherapy (such as cyclophosphamide or melphalan)
steroids (such as prednisolone or dexamethasone)
The particular combination depends on whether a patient may be suitable for autologous hematopoietic cell transplantation or not.
Autologous hematopoietic cell transplantation
involves the removal of a patient’s own stem cells prior to chemotherapy, which are then replaced after chemotherapy
prolong both event-free and overall survival when compared with non-transplant strategies
typically it is younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.
symptom management and complication avoidance myeloma
pain: treat with analgesia (using the WHO analgesic ladder)
pathological fracture: zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.
infection
patients receive annual influenza vaccinations
they may also receive Immunoglobulin replacement therapy.
venous thromboembolism prophylaxis
fatigue
treat all possible underlying causes
if symptoms persist consider an erythropoietin analogue.
coeliac vaccination
Patients with coeliac disease often have a degree of functional hyposplenism
For this reason, all patients with coeliac disease are offered the pneumococcal vaccine
Coeliac UK recommends that everyone with coeliac disease is vaccinated against pneumococcal infection and has a booster every 5 years
Currrent guidelines suggest giving the influenza vaccine on an individual basis.
features specific to haemolytic anaemias
Splenomegaly (the spleen becomes filled with destroyed red blood cells)
Jaundice (bilirubin is released during the destruction of red blood cells)
important invetsigations haemolytic anaemias
Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells - Schistocytes are a key finding on the blood film in patients with microangiopathic haemolytic anaemia)
Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)
what is hereditary elliptocytosis
Hereditary elliptocytosis is similar to hereditary spherocytosis except that the red blood cells are ellipse-shaped. It is also autosomal dominant. The presentation and management are the same as hereditary spherocytosis.
what test would be positive autoimmune haemolytic anemia
direct coombs
warm vs cold autoimmune haemolytic anaemia
Warm autoimmune haemolytic anaemia is the more common type. Haemolysis occurs at normal or above-normal temperatures. It is usually idiopathic, meaning that it arises without a clear cause.
Cold AIHA can be secondary to lymphoma, leukaemia, systemic lupus erythematosus and infections (e.g., mycoplasma, EBV, CMV and HIV).
management autoimmune haemolytic anaemias
Blood transfusions
Prednisolone
Rituximab (a monoclonal antibody against B cells)
Splenectomy
what anaemia has red urine in the morning
Paroxysmal Nocturnal Haemoglobinuria
acquired genetic mutation
what does microangiopathic haemolytic anameia mean?
Microangiopathic haemolytic anaemia (MAHA) involves the destruction of red blood cells as they travel through the circulation.
This is most often caused by abnormal activation of the clotting system, with blood clots (thrombi) partially obstructing the small blood vessels, referred to as thrombotic microangiopathy. These obstructions churn the red blood cells, causing haemolysis (rupture). Picture a mesh inside the small blood vessels shredding the red blood cells.
causes microangiopathic haemolytic anemia
Haemolytic uraemic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopenic purpura (TTP)
Systemic lupus erythematosus (SLE)
Cancer
blood film finding micronangiopathic haemolysis
Schistocytes
pathophysiology and triad haemolytic uraemic syndrome
Occurs when there is thrombosis within small blood vessels throughout the body.
This is usually triggered by a bacterial toxin called shiga toxin. It leads to the classic triad of:
Haemolytic anaemia: anaemia caused by red blood cells being destroyed
Acute kidney injury: failure of the kidneys to excrete waste products such as urea
Thrombocytopenia: low platelet count
cause HUS? exacerbating factors?
The most common cause is a toxin produced by the e. coli 0157 bacteria, called the shiga toxin. Shigella also produces this toxin.
The use of antibiotics and anti-motility medications such as loperamide to treat gastroenteritis caused by these pathogens increases the risk of developing HUS.
features HUS
Reduced urine output
Haematuria or dark brown urine
Abdominal pain
Lethargy and irritability
Confusion
Oedema
Hypertension
Bruising
management HUS
HUS is a medical emergency and has a 10% mortality. It needs to be managed by experienced paediatricians under the guidance of a renal specialist. The condition is self limiting and supportive management is the mainstay of treatment:
Urgent referral to the paediatric renal unit for renal dialysis if required
Antihypertensives if required
Careful maintenance of fluid balance
Blood transfusions if required
70 to 80% of patients make a full recovery.
pathophysiology TTP
TTP is caused by a deficiency in ADAMTS13, a metalloprotease that cleaves von Willebrand factor multimers. This leads to the accumulation of ultra-large von Willebrand factor multimers, which promote platelet aggregation and thrombus formation.
In TTP, hemolytic anemia develops because red blood cells are broken into pieces as they try to squeeze around blood clots. (microangiopathic haemolytic anemia)
Deficiency in the ADAMTS13 protein can be due to:
An inherited genetic mutation (hereditary)
Autoimmune disease, where antibodies are created against the protein (acquired)
Post-infection e.g. urinary, gastrointestinal
Pregnancy
Drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
Tumours
SLE
HIV
pentad TTP
Microangiopathic haemolytic anaemia
Fever
Disturbed neurological function
Renal failure
Thrombocytopenia
management TTP
Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab.
No antibiotics - may worsen outcome
Plasma exchange is the treatment of choice
Steroids, immunosuppressants
Vincristine
what kind of anaemia can prostehtic valves cause?
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement, although it varies depending on the type. It is caused by turbulence flow around the valve and the shearing of the red blood cells. The valve churns up the cells, and they break down.
Management involves:
Monitoring
Oral iron and folic acid supplementation
Blood transfusions if severe
Revision surgery may be required in severe cases
diagnosis of coeliac process
- anti ttg, anti-EMA, total IgA
if all neg and done them all = coeliac ruled out
if positive –> refer to gastro for confirmation using endoscopy duodenal biopsy
has to be on gluten containing diet
Spherocytes on blood film
- hereditary spherocytosis
- autoimmune haemolytic anaemia
Calcium level myeloma
Hypercalcaemia,
In cases of myeloma, there is hypercalcaemia secondary to increased osteoclast activity. Additionally, renal impairment causes hypercalcaemia and hyperphosphataemia.
Phosphate level myeloma
normal / high phosphate
renal impairment causes hypercalcaemia and hyperphosphataemia
ALP myeloma
normal ALP
ALP enzyme levels remain normal with myeloma but may rise in other conditions such as solid tumours or bony metastases.
Most likely diagnosis Pancytopaenia 5 years post-chemotherapy/radiotherapy
Myelodysplastic syndrome
abdominal pain and a motor periperal neuropathy
Leas poisoning
Haemoglobin electrophoresis results beta thalassemja major
HbA2 (an alpha chain) & HbF raised
HbA absent
What diabetes drug is contraindicated in G6PD deficiency
Glipizide
As it is a sulfonylurea
G6PD deficiency: sulph- drugs: sulphonamides, sulphasalazine and sulfonylureas can trigger haemolysis
What does Disproportionate microcytic anaemia mean and what does it indicate
It means the MCV and the Hb are decreased disproportionately. This is a sign of beta thalassemia
This is in contrast to iron deficiency where the MCV and Hb are usually proportionally decreased.
when should you get blood results within 48 hours for ?haematological malignancy in a young person (0-24 years)
Any of the following features in a person aged 0-24 years should prompt a very urgent full blood count (within 48 hours) to investigate for leukaemia:
Pallor
Persistent fatigue
Unexplained fever
Unexplained persistent infections
Generalised lymphadenopathy
Persistent or unexplained bone pain
Unexplained bruising
Unexplained bleeding
when should you refer for immediate specialist assessment for leukaemia in a young person (0-24 years)
if: unexplained petechiae or hepatosplenomegaly
