1. Anaemia Flashcards

Question

what do patients with newly diagnosed colorectal cancer need for staging

Answer 1

carcinoembryonic antigen (CEA) CT of the chest, abdomen and pelvis

Answer 2

Colonoscopy

Answer 3

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

Answer 4

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

Answer 5

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.

Answer 6

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

Answer 7

3 years Serum carcinoembryonic antigen (CEA) CT thorax, abdomen and pelvis

Answer 8

5% hereditary non-polyposis colorectal carcinoma (HNPCC, 5%) familial adenomatous polyposis (FAP, <1%)

Answer 9

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.

Answer 10

post-menopausal bleeding is the classic symptom pre-menopausal women may have a change intermenstrual bleeding haematuria pain and discharge are unusual features

Answer 11

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

Answer 12

first-line investigation is trans-vaginal ultrasound - a normal endometrial thickness (< 4 mm) has a high negative predictive value hysteroscopy with endometrial biopsy

Answer 13

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

Answer 14

1. 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.

Answer 15

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.

Answer 16

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

Answer 17

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

Answer 18

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.

Answer 19

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)

Answer 20

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).

Answer 21

Advanced disease may present with additional signs, such as palpable abdominal mass, ascites, and supraclavicular lymphadenopathy (Virchow's node).

Answer 22

High Cancer is believed to induce platelet formation through the release of interleukin 6, a proinflammatory cytokine that stimulates the production of thrombopoietin hormone.

Answer 23

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)

Answer 24

Chemo Radiation Surgery

Answer 25

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

Answer 26

FBC - normocytic anaemia then microcytic as iron is depleted

Answer 27

Fe low Ferritin low TIBC high Transferrin saturations low

Answer 28

Fe low Ferritin high (stored iron cant be utilised) TIBC low (stored iron cant be utilised) Transferrin saturations low

Answer 29

Don't respond to iron therapy Treat underlying disorder

Answer 30

Inherited gene defect Acquired alcohol excess lead poisoning Copper deficiency B6 deficiency Drugs Myelodysplasia / AML

Answer 31

Abdominal pain, peripheral neuropathy motor, blue lines on gum margin

Answer 32

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

Answer 33

Fe high Ferritin high TIBC low Transferrin saturations high

Answer 34

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

Answer 35

Hepatosplenomegaly is found in a third to a half of people with sideroblastic anaemia and is not present in iron deficiency anaemia.

Answer 36

Stop offending agent Pyridoxine (B6) supplement - cofactor in gene pathway

Answer 37

autosomal recessive

Answer 38

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).

Answer 39

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)

Answer 40

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.

Answer 41

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

Answer 42

Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation.

Answer 43

chromosome 16

Answer 44

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

Answer 45

2 alleles missing - minor anaemia

Answer 46

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.

Answer 47

4 missing alleles alpha thalassemia incompatible with life usually die in utero hydrops fetalis

Answer 48

Southeast Asia, the Middle East, China, and in those of African descent.

Answer 49

chromosome 11

Answer 50

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

Answer 51

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

Answer 52

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

Answer 53

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.

Answer 54

Beta thalassemia most often occurs in people of Mediterranean origin. To a lesser extent, Chinese, other Asians, and African Americans can be affected.

Answer 55

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

Answer 56

beta major

Answer 57

hypersegmented neutrophils - (more than 5 lobes)

Answer 58

1. Check folate and B12 levels 2. If normal : non megaloblastic causes (liver disease, alcohol, hypothyroid, reticulocytosis)

Answer 59

Megaloblastic anaemia results from impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.

Answer 60

Pernicious anaemia accounts for 80% of cases of megaloblastic anaemia due to impaired absorption of vitamin B12.

Answer 61

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

Answer 62

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

Answer 63

bilateral dorsal column signs, may have bilateral corticospinal tract signs (affects posterior cord)

Answer 64

Always replace vitamin B12 before folate - giving folate to a patient deficient in B12 can precipitate subacute combined degeneration of the cord

Answer 65

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

Answer 66

Anti-intrinsic factor antibodies for pernicious anaemia Anti-parietal cell antibodies (to confirm/refute if anti-intrinsic antibodies negative)

Answer 67

gastric cancer

Answer 68

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

Answer 69

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.

Answer 70

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.

Answer 71

Check vitamin B12 levels in all people before starting folic acid ALWAYS CORRECT B12 BEFORE FOLATE

Answer 72

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

Answer 73

HLA-DQ2 gene (90%) HLA-DQ8 gene

Answer 74

Tissue transglutaminase antibodies (anti-TTG) Endomysial antibodies (EMAs)

Answer 75

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.

Answer 76

“Crypt hypertrophy” “Villous atrophy”

Answer 77

duodenum classically. jejunum most affected

Answer 78

1. auto-antibody testing Tissue transglutaminase antibodies (anti-TTG) Endomysial antibodies (EMAs) 2. 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.

Answer 79

Type 1 diabetes Thyroid disease Autoimmune hepatitis Primary biliary cirrhosis Primary sclerosing cholangitis Down’s syndrome

Answer 80

Vitamin deficiency Anaemia Osteoporosis Ulcerative jejunitis Enteropathy-associated T-cell lymphoma (EATL) of the intestine Non-Hodgkin lymphoma (NHL) Small bowel adenocarcinoma (rare)

Answer 81

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.

Answer 82

The low thyroid hormone levels of hypothyroidism suppress the activity of bone marrow, the tissue that makes red blood cells.

Answer 83

TSH is raised, and T3 and T4 are low

Answer 84

anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies

Answer 85

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.

Answer 86

Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (including oedema, pleural effusions and ascites) Heavy or irregular periods Constipation

Answer 87

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

Answer 88

Hashimoto’s thyroiditis can initially cause a goitre, after which there is atrophy (wasting) of the thyroid gland.

Answer 89

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.

Answer 90

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

Answer 91

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

Answer 92

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

Answer 93

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

Answer 94

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.

Answer 95

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.

Answer 96

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

Answer 97

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)

Answer 98

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

Answer 99

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.

Answer 100

↓ 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.

Answer 101

acute episodes of haemolysis neonatal jaundice gallstones splenomegaly failure to thrive

Answer 102

X-linked grandpa- dad

Answer 103

Heinz bodies on blood films. Bite and blister cells may also be seen

Answer 104

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

Answer 105

anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas acute illness DKA fava (broad) beans

Answer 106

Mediterranean and Africa

Answer 107

northern European descent

Answer 108

autosomal diminant

Answer 109

1. 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 2. EMA binding test and the cryohaemolysis test 3. for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Answer 110

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

Answer 111

acute haemolytic crisis: treatment is generally supportive transfusion if necessary longer term treatment: folate replacement splenectomy

Answer 112

<24 hours PATHOLOGICAL - check bilirubin level and do peripheral blood smear

Answer 113

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

Answer 114

parvovirus infection

Answer 115

raised mean corpuscular haemoglobin concentration [MCHC] increase in reticulocytes

Answer 116

Symptoms in homozygotes don't tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.

Answer 117

autosomal recessive HbAA = normal HbAS = sickle cell trait HbSS = sickle cell disease

Answer 118

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

Answer 119

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.

Answer 120

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

Answer 121

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

Answer 122

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

Answer 123

follow care plan 1. prescribe paracetamol and/or ibuprofen (avoid ibuprofen if the person has renal impairment or significant proteinuria). 2. 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

Answer 124

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.

Answer 125

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).

Answer 126

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.

Answer 127

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

Answer 128

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).

Answer 129

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.

Answer 130

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.

Answer 131

encapsulated bacteria, in particular Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae. due to reduced fucntion of spleen

Answer 132

CKD: low reticulocyte Blood loss : high reticulocyte Aplastic anaemia : low reticulocyte

Answer 133

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

Answer 134

Aplastic is a rare condition characterised by pancytopenia and a hypoplastic bone marrow.

Answer 135

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)

Answer 136

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).

Answer 137

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

Answer 138

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.

Answer 139

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%

Answer 140

autosomal recessive

Answer 141

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.

Answer 142

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.

Answer 143

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

Answer 144

acute myelogenous leukemia (AML), MDS, and liver tumors.

Answer 145

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).

Answer 146

acute lymphoblastic leukemia

Answer 147

acute lymphoblastic leukemia

Answer 148

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)

Answer 149

An urgent full blood count

Answer 150

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)

Answer 151

due to leukemic infiltration

Answer 152

a build-up of large numbers of cancerous cells which have travelled from the bone marrow

Answer 153

They recommend children or young people with petechiae or hepatosplenomegaly are sent for immediate specialist assessment.

Answer 154

- FBC - lactate - bone marrow biopsy - CT and PET scans - lymph node biopsy - genetic tests

Answer 155

- 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)

Answer 156

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.

Answer 157

Richter’s transformation refers to the rare transformation of CLL into high-grade B-cell lymphoma.

Answer 158

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

Answer 159

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.

Answer 160

from middle age onwards

Answer 161

myeloprolifertaive disorder such as polycythaemia vera or myelofibrosis

Answer 162

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.

Answer 163

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

Answer 164

Failure to treat cancer Stunted growth and development in children Infections due to immunosuppression Neurotoxicity Infertility Secondary malignancy Cardiotoxicity (heart damage) Tumour lysis syndrome

Answer 165

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.

Answer 166

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

Answer 167

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

Answer 168

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.

Answer 169

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

Answer 170

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)

Answer 171

JAK2 MPL CALR

Answer 172

JAK2 inhibitors, such as ruxolitinib.

Answer 173

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

Answer 174

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)

Answer 175

older age and previous chemotherapy or radiotherapy.

Answer 176

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)

Answer 177

Full blood count will be abnormal. There may be blasts on the blood film. Bone marrow biopsy is required to confirm the diagnosis.

Answer 178

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)

Answer 179

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.

Answer 180

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.

Answer 181

is where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.

Answer 182

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,

Answer 183

PC: anaemia PC: neutropenia PC: thrombocytopenia PC: pathological fractures PC: bone pain, particularly back pain PC: myeloma renal disease PC: hyperviscosity PC: kidney stones

Answer 184

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

Answer 185

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.

Answer 186

involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy

Answer 187

Allogenic hematopoietic cell transplantation is not commonly used in myeloma due to high rates of overall mortality and symptoms of graft-ve

Answer 188

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.

Answer 189

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.

Answer 190

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.

Answer 191

Splenomegaly (the spleen becomes filled with destroyed red blood cells) Jaundice (bilirubin is released during the destruction of red blood cells)

Answer 192

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)

Answer 193

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.

Answer 194

direct coombs

Answer 195

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).

Answer 196

Blood transfusions Prednisolone Rituximab (a monoclonal antibody against B cells) Splenectomy

Answer 197

Paroxysmal Nocturnal Haemoglobinuria acquired genetic mutation

Answer 198

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.

Answer 199

Haemolytic uraemic syndrome (HUS) Disseminated intravascular coagulation (DIC) Thrombotic thrombocytopenic purpura (TTP) Systemic lupus erythematosus (SLE) Cancer

Answer 200

Schistocytes

Answer 201

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

Answer 202

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.

Answer 203

Reduced urine output Haematuria or dark brown urine Abdominal pain Lethargy and irritability Confusion Oedema Hypertension Bruising

Answer 204

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.

Answer 205

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

Answer 206

Microangiopathic haemolytic anaemia Fever Disturbed neurological function Renal failure Thrombocytopenia

Answer 207

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

Answer 208

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

Answer 209

1. 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

Answer 210

- hereditary spherocytosis - autoimmune haemolytic anaemia

Answer 211

Hypercalcaemia, In cases of myeloma, there is hypercalcaemia secondary to increased osteoclast activity. Additionally, renal impairment causes hypercalcaemia and hyperphosphataemia.

Answer 212

normal / high phosphate renal impairment causes hypercalcaemia and hyperphosphataemia

Answer 213

normal ALP ALP enzyme levels remain normal with myeloma but may rise in other conditions such as solid tumours or bony metastases.

Answer 214

Myelodysplastic syndrome

Answer 215

Leas poisoning

Answer 216

HbA2 (an alpha chain) & HbF raised HbA absent

Answer 217

Glipizide As it is a sulfonylurea G6PD deficiency: sulph- drugs: sulphonamides, sulphasalazine and sulfonylureas can trigger haemolysis

Answer 218

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.

Answer 219

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

Answer 220

if: unexplained petechiae or hepatosplenomegaly