Haematology Flashcards

Question

SCD investigations

Answer 1

Bloods: Hb 60-90g/L, reticulocytes 10-20%, high bilirubin. Haemolysis variable Film: sickle cell and target cells Sickle solubility test +ve but doesn't distinguish between types Hb electrophoresis confirms diagnosis Pregnant women at risk of being carriers are offered testing during pregnancy Newborn screening heel prick test at 5 days of age XR: vaso-occlusive crisis can shoe osteonecrosis, subperiosteal and epidural haemorrhage, hand-foot syndrome (dactylics), growth disturbance, osteomyelitis or marrow hyperplasia in anaemia

Answer 2

``` Anaemia Increase infection risk Stroke Avascular necrosis in large joints Pulmonary HTN Painful and persistent penile erection (priapism) CKD Sickle cell crisis Acute chest syndrome ```

Answer 3

Umbrella term for spectrum of acute crises related to condition. Range from mild to life threatening, can occur spontaneously or triggered by stresses such as infection, dehydration, cold or significant life events. There is no specific treatment for sickle cell crises and they are managed supportively: Have a low threshold for admission to hospital Treat any infection Keep warm Keep well hydrated (IV fluids may be required) Simple analgesia such as paracetamol and ibuprofen Penile aspiration in priapism Avoid NSAIDs (ibuprofen) in renal impairment

Answer 4

Commonly occurs from microvascular occlusion causing distal ischaemia Can be triggered by cold, dehydration, infection or hypoxia Associated with dehydration and raised haematocrit Symptoms typically include pain, fever, those of triggering infection Bone marrow infarction causes severe skeletal pain; osteomyelitis presents with localised pain and systemic features of infection Hands and feet show dactylitis (inflammation of finger or toes) Mesenteric ischemia results in acute abdomen presentation CNS infarction results in stroke, seizures, cognitive defects Splenic infarction - susceptibility to infection (40% SCD childhood deaths) Poor growth, chronic renal failure, gallstones, retinal disease, iron overload Lung damage from hypoxia causing fibrosis and pulmonary HTN Can cause priapism in men by trapping blood in penis causing painful and persistent erection (urological emergency treated with aspirin of blood from penis) Management: no specific treatment are managed supportively IV opiates, haematologist advice, G+S bloods, FBC, reticulocyte count, septic screen (Blood cultures, MSU + CXR), Rehydrate (IV fluids) and keep warm, NSAIDs and paracetamol analgesia oxygen PRN, consider empirical antibiotics if fever >38, unwell or chest signs Penile aspiration if priapism (urological emergency)

Answer 5

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 a severe anaemia and circulatory collapse (hypovolaemic shock). 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 and therefore susceptibility to infections.

Answer 6

Aplastic crisis describes a situation where there is a 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. Hand foot syndrome: Occurs in 50% children with SCD Most common between 6 months and 6 YO Usually have systemic symptoms of fever, elevated WCC Characterised by swelling of hands and feet (uni or bilateral) Usually self limiting

Answer 7

A diagnosis of acute chest syndrome requires: Fever or respiratory symptoms with New infiltrates seen on a chest xray This can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli). Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause: 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 8

Cord blood taken at birth Ensure vaccination up to date Avoid dehydration and other triggers of sickle cell crisis Pneumococcal prophylaxis (vaccine +/- penicillin V) Hydroxycarbamide to stimulate HbF production which does not lead to sickling of RBCs (protective against sickle cell crisis and acute chest syndrome) Blood transfusions for severe anaemia Bone marrow transplant can be curative Referral to hematologist for chronic management Prevention: genetic counselling, parental tests and education can prevent 90% deaths form crisis acute sickle cell crises protocol: - analgesia - haematologist early intervention - septic screen: blood cultures, MSU, CXR - rehydrate with IV fluids and keep warm - oxygen PRN - consider early empirical antibiotics if temperature, unwell or chest signs

Answer 9

Condition where the body does not produce enough blood cells Leaves the patient fatigued, prone to infection and uncontrolled bleeding Rare and serious condition, can develop at any age, suddenly or gradually worsen over time, can be mild or severe Can be short term or develop into chronic condition Cause: radio/chemotherapy Exposure to toxic chemicals like pesticides, insecticides, benzene Use of certain drugs (RA and some antibiotics) Autoimmune disorders Viral infection: hepatitis, epstein-barr, cytomegalovirus, parvovirus B19 and HIV Pregnancy Idiopathic Associations: Paroxysmal nocturnal hemoglobinuria: RBCs break down too soon which can lead to aplastic anaemia or vice versa Fanconi’s anaemia (rare) inherited disease that leads to aplastic anaemia. Tend to have many birth defects

Answer 10

``` radio/chemotherapy Exposure to toxic chemicals Drugs Family history Pregnancy (rare) ``` ``` Symptoms: Fatigue SOB Rapid irregular HR Pallor Frequent or prolonged infections Unexplained or easy bruising Nosebleeds or bleeding gums Prolonged clotting time Skin rashes Dizziness Headache Fevers ```

Answer 11

Diagnosis: Bloods: FBC (RBC, WCC, platelets all decreased) Bone marrow biopsy (few blood cells present) Management: Depend on age and severity of condition Anaemia caused by radio or chemotherapy may cease with treatment cessation Pregnant women treated with blood transfusions and often improves once pregnancy ends Severe is life threatening and needs immediate hospitalisation Blood transfusion of RBC and platelets (complications can arise from multiple transfusions) Stem cell transplant Immunosuppressants (gengraf, noral, sandimmune), steroids (methylprednisolone) Bone marrow stimulants: sargramostim, filgrastim, pegfilgrastim often used with immune suppressing drugs Antibiotics and antivirals prophylaxis

Answer 12

Multi Genetic disorder associated with HLA types DQ2 (90%) or DQ8, plus other genetic or environmental factors. Family tendency 10-15% Approx 1 in 100 people in the UK have coeliac disease, however only 10-20% will be diagnosed Highest incidence in ages 50-69

Answer 13

wide variation of signs and symptoms, many cases are asymptomatic Persistent unexplained abdominal or GI symptoms Faltered growth Unexpected weight loss Severe or persistent mouth ulcers Unexplained iron, vit B12 or folate deficiency Type 1 diabetes Autoimmune thyroid disease IBS in adults 1st degree relatives of people with coeliac disease Dermatitis herpetiformis (classic manifestations of CD) Gluten sensitivity NICE recommends serological testing for coeliac disease in people with the following: Metabolic bone disorder Unexplained neuro symptoms (ataxia, epilepsy, dementia, depression) Unexplained subfertility or recurrent miscarriage Persistently raised liver enzymes without known cause Dental enamel defects Down’s or Turner syndrome All newly diagnosed type 1 diabetics are screened for coeliac disease*

Answer 14

**only accurate if gluten diet is eaten during diagnostic process** Autoantibodies: total IgA and tTG 1st line. IgA EMAs if weakly positive. For children: total TgA and IgA tTG 1st line. IgG EMA, IgG DGP or tTG if IgA is deficient FBC: anaemia, iron and folate deficiency, B12, ferritin, LFTs (elevated transaminases which should return to normal on gluten free diet), Ca and albumin Small bowel barium studies to exclude other causes of malabsorption Biopsy needed for confirmation by GI endoscopy or suction capsule

Answer 15

Referrals to GI specialist: Young people with +ve serological tests for endoscopic biopsy Children with +ve serology to paediatric specialist for further investigation -Ve serology to gastro specialist if CD still suspected for further investigation management: Gluten free diet (no wheat, barely, rye, bread, cakes etc) seems to be only effective treatment Refractory CD: consider prednisolone initial management while waiting specialist advice If after GFD excluded but symptoms persist/serology is high for >12 months refer for endoscopic biopsy Annual review to measure weight, height, review symptoms, assess diet and adherence, need for specialist dietitian or nutritional advice Consider DEXA scan, regular bloods for long term complications monitoring ``` complications: Deficiencies eg vit D and iron Osteoporosis Cancer Ulcerative jejunitis Functional hyposplenism Anxiety, depression Male infertility Poor foetal outcome in UNDIAGNOSED pregnancy women, but not diagnosed ```

Answer 16

Medical condition in which RBC count and/or Hgb is less than normal Not a disease in itself instead may reflect underlying disease process and must be considered in relation to patients age and gender Hb <13.5g/dl (adult male) or <11.5g/dl (adult female), varies in children based on age group Aetiology: Decrease in RBC production: iron & B12 deficiencies, aplastic anaemia, CKD (decreased erythropoiesis) Increase in RBC destruction: sickle cell anaemia, G6PD deficiency, spherocytosis, Increased RBC loss: bleeding (acute or chronic)

Answer 17

FBC: Hb level (men <13.0g/dl; female 11.5 g/dl; pregnancy - 11g/dl ((dilutional effect from increased circulating plasma making RBC % smaller in proportion))) MCV (blood film): microcytic anaemia (MCV <80 femtolitres), normocytic (MCV 80-100 femtolitres), macrocytic anaemia (MCV >100 femtolitres); always look at these values when someone is presenting with anaemia (Low Hb); these values may vary based on labs so always look at reference ranges Classification based on aetiology: Nutrient deficiency or depletion (most common worldwide): iron Fe, folate def, B12 def. Blood loss: acute (reticulocytosis (6hrs) causing normocytic anaemia) or chronic (ongoing iron loss causing microcytic anaemia) Acquired bone marrow disease: aplastic anaemia (inherited bone marrow failure), autoimmune destruction of bone marrow cells Chronic systemic disease: normocytic anaemia or in severe cases microcytic anaemia when coexisting with iron deficiency anaemia Chronic kidney disease: main cause is decreased erythropoietin production leading to decrease RBC production causing norm/microcytic anaemia Chronic liver disease: intravascular dilution leading to macrocytic anaemia Autoimmune haemolytic anaemia: RBCs attacked by autoantibodies causing destruction (SLE, RA or scleroderma) Genetic disorders (haemoglobinopathies): thalassaemias: group of autosomal recessive conditions resulting in decreased/absent alpha globin (alpha thalassaemia) or beta globin chains in the Hb molecule. Leads to RBC destruction and hemolytic anaemia. Sickle cell: haemolytic anaemia.

Answer 18

``` TAILS Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Sideroblastic anaemia ```

Answer 19

``` 3As 2Hs: Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism ```

Answer 20

(deficiencies) B12 deficiency Folate deficiency ``` Normoblastic macrocytic: DARHL Drugs such as azathioprine Alcohol Reticulocytosis (usually from haemolytic anaemia or blood loss) Hypothyroidism Liver disease ```

Answer 21

``` Very nonspecific pallor/jaundice Fatigue Dyspnea Palpitations Anorexia Headaches Features of underlying disease Pica: dietary craving for inedible things like clay, dirt etc. Hair loss - iron deficiency anaemia ``` Signs: Koilonychia is spoon shaped nails and can indicate iron deficiency Angular chelitis can indicate iron deficiency Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency Brittle hair and nails can indicate iron deficiency Jaundice occurs in haemolytic anaemia Bone deformities occur in thalassaemia Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease

Answer 22

Hb level Blood film: MCV, MCH, MCHC Haematocrit (Hct) aka packed cell volume (PCV): measures proportion of blood:other cells Haemoglobin electrophoresis: screen test to identify normal and abnormal Hb and assess quantity Coeliac serology: presence of anti-endomysial antibody or tissue transglutaminase antibody for patient with iron deficiency anaemia (IDA) FIT for those >50, IDA, weight loss OR <60 with abdominal mass Blood serum level of ferritin, total iron binding capacity (TIBC), iron, B12 and folate Reticulocyte count: normal 2%: quantitative measure of concentration of immature RBC in circulation. If LOW: due to decreased production such as bone marrow disease (aplastic anaemia). If elevated: reflects bone marrow response to increased RBC destruction (haemolysis). Means the bone marrow producing RBCs too fast resulting in mass immature RBCs (reticulocytes) OGD and colonoscopy to investigate for GI cause of unexplained iron deficiency anaemia (urgent referral) Bone marrow biopsy is cause unclear Target cells - abnormal RBC seen in liver disease, normal shape but abnormal centre. Nonspecific sign for abnormal RBC production

Answer 23

serum iron: measures circulating iron most of which bound to transferrin. low in iron deficiency anaemia but also anaemia of chronic disease total iron binding capacity TIBC: circulating transport protein for iron. Low iron = high binding capacity due to need for it High iron = low binding capacity transferrin saturation (TSAT): ratio of serum iron to TIBC. decreased in iron deficiency anaemias ferritin: circulating iron storage protein. also an acute phase reactant increases independently of iron storage in inflammatory disorders, infection, liver disease, heart failure and malignancy Very low iron deficiency anaemias can be normal in severely iron deficient patients who are very unwell

Answer 24

Foetal haemoglobin = HbF Up to 6 months switches to HbA and HbA2 (adult Hb) The majority is HbA; around 2% is HbF and HbA2 Sickle cell: presence of HbS cells instead of HbA as majority Beta thalassaemia: majority of RBCs remains HbF with little HbA and HbA2

Answer 25

FBC and peripheral blood smear examinations: MCV <80 - microcytic anaemia Request serum iron studies - low iron and ferritin with high TIBC - iron deficiency anaemia. If low/normal iron and low/normal ferritin with low TIBC - suggests component of anaemia of chronic disease with iron deficiency anaemia MCV 80-100 - normocytic anaemia. Request reticulocyte count - if <2% (hypoproliferative) - suggests leukaemia, aplastic anaemia, pure RBC aplasia or other bone marrow failure syndromes If >2% (hyper proliferative) - suggests haemorrhage or haemolytic anaemias MCV >100 (macrocytic anaemia) - are the cells megalocytes and segmented neutrophils on peripheral smear?? If present megablastic - suggests vitamin B12 and/or folate deficiency or drug induced anaemia If absent: non-megaloblastic. suggests alcohol abuse, myelodysplastic syndrome, liver disease, congenital bone marrow failure syndromes

Answer 26

Megaloblastic: B12 deficiency Folate deficiency ``` Non-megaloblastic: Reticulocytes Liver disease Hypothyroid Pregnancy ```

Answer 27

Hydroxocobalamin Vitamin B12 deficiency: causes macrocytosis. DNA synthesis requires B12 cofactor therefore deficiency leads to decreased erythrocyte DNA synthesis resulting in macrocytosis. Hydroxocobalamin body stores are sufficient to last for anywhere between 2-5 years depending on need. Absorbed in the ileum after binding to intrinsic factor Crohn’s disease is most likely IBD cause of B12 deficiency as this affects the entire GIT NOT ulcerative colitis as this is limited to the colon only Serum cobalamin (B12) of <200nanograms/L (148 picomol/L) In elderly B12 may be 10-160 picomol/L with no anaemia Women taken OCPs may have lower B12 but no anaemia

Answer 28

Dietary deficiency is rare and usually only occurs in elderly, those on strict vegan or vegetarian diets Other causes of B12 deficiency: lack of intrinsic factor in patients who have undergone gastrectomy or have pernicious anaemia Malabsorption of B12 secondary to small bowel bacterial overgrowth, tapeworm, ringworm, familial factors, Crohn’s, celiac or drugs like PPIs, metformin or H2 receptor antagonist. Crohn’s disease is most likely IBD cause of B12 deficiency as this affects the entire GIT NOT ulcerative colitis as this is limited to the colon only Pernicious anaemia: autoimmune condition affects the gastric mucosal lining leading to mucosal atrophy. Reduced number of parietal cells which secrete intrinsic factor (IF) which is essential for Vit B12 absorption. If +ve they definitely have anaemia, but if -ve recheck in 12 months or so to see if Abs have developed. Or anti parietal cell antibodies are present (can be present in elderly without pernicious anaemia) People with pernicious anaemia are at increased risk of gastric cancer and thyroid disease so must be screened for thyroid function annually and have regular colonoscopy/any bowel red flags immediately investigated

Answer 29

``` Fatigue Weakness Irritability Exercise intolerance Exertional dyspnoea (concerning at rest) Neuro involvement: Loss of cutaneous sensation Muscle weakness Optic neuropathy Vertigo Psychiatric disturbance: mild neurosis to severe dementia Symmetrical neuropathy, affecting legs more than arms Ataxia Paraesthesia ```

Answer 30

FBC: macrocytic anaemia with hypersegmented neutrophils and/or oval macrocytes Serum Vitamin B12 <200ng/L or high clinical suspicion on vit B12 deficiency. B12 acts as a coenzyme that converts MMA to other substances; therefore is increased in B12 def. And can indicate functional B12 deficiency. However in CKD this is always elevated so must only be used in renal functioning pts. Non dietary cause suspected: intrinsic factor antibodies (IFAB)

Answer 31

Based on vit B12 level (<200ng/l) and presence/absence of neurological symptoms No neurological symptoms: IM hydroxocobalamin 1mg 3 x weekly for 2 weeks If dietary cause: oral cyanocobalamin 50-150mcg daily (OTC) and dietary advice for B12 rich foods (eggs, meat) Non-dietary cause: IM hydroxocobalamin 1000mcg every 3 months for life Neurological involvement: urgent referral to haematology, loading dose vit B12 (hydroxocobalamin 1mg IM STAT every other day) Complications of Vit B12 deficiency: Neurological symptoms: paraesthesia, ataxia, progressive symmetrical neuropathy which affects the legs more than the arms, numbness, poor motor coordination, memory lapses, age related impairment Severe psychiatric symptoms (rare)

Answer 32

Folate is also needed as a cofactor in DNA synthesis. Folate deficiency can be caused by: dietary deficiency, increased need in pregnancy, congenital deficiency, alcoholism, increased turnover in conditions like haemolysis or SCD etc. Serum folate of <7 nanomol/L (3micrograms/L) is used as a guide to indicate folate deficiency. 7-10 is indicative of deficiency but not diagnostic of anaemia Folate is absorbed through upper part of small intestine (again only crohn’s could cause not ulcerative colitis) and stores last around 4 months Causes: Pregnancy Malignancy e.g. leukaemia, lymphoma Blood disorders (SCD, haemolytic anaemia) Drugs: nitrofurantoin/trimethoprim, anticonvulsants, methotrexate Malabsorption: IBD (crohn’s only) and reduced dietary intake

Answer 33

``` Serum folate (only reflets recent stores) MUST test B12 levels also due to risk of subacute combined degeneration of spinal cord, secondary to vitamin B12 deficiency. Presents with weakness of legs, arms, tingling and numbness progressively worsen, visual changes, psychiatric changes. ``` management: Folic acid 5mg PO OD for 4 months, reassess iron studies and reduce to maintenance dose of 5mg every 1-7 days

Answer 34

Affects large portion of the population especially women of childbearing age and those in low/middle income countries You can be iron deficiency without anaemia Normally 4-5 g iron in the body with no mechanism to regulate its excretion Can be toxic in excess so absorption is controlled 25% stored in reticuloendothelial systems as protein complexes, ferritin and hemosiderin 0.1% bound to transferrin in plasma 4.9% in myoglobin, cytochromes and other enzymes Majority is used to make haemoglobin Causes: Blood loss: GI (malignancy, telangiectasia, gastritis), menorrhagia (common cause), pregnancy or haematuria Reduced intake: unlikely in western world (neglect) Reduced absorption: coeliac disease, autoimmune gastritis or H. pylori infection **always assess for malignancy to rule out first**

Answer 35

Pathology: Iron stores begin to deplete but no anaemia initially due to storage use. May show mild fatigue without any gross Hb changes. MCV and MCH normal Ferritin (storage) begins to fall, Hb remains stable and MCV/MCH remain normal Mild anaemia (Hb >100g/l) and mild hypochromia (reduced MCH - always look at this!) Moderate anaemia and hypochromia (reduced MCH) and microcytic (reduced MCV)

Answer 36

``` Fatigue Weakness Irritability Exercise intolerance Exertional dyspnea Headache Vertigo Angina like symptoms Pica: compulsion to eat substances not fit as food (clay/dirt) or craving ice Conjunctival pallor Angular stomatitis Atrophic glossitis (red, shiny tongue) Koilonychia (spoon nails) ```

Answer 37

``` Bloods: FBC (MCH, MCV, MCHC) blood film Ferritin: low in iron deficiency anaemia but can be normal in SEVERELY iron deficient patients who are very unwell (acute phase reactant goes up in inflammatory condition; doesn’t stay raised in chronic disease). LOW = all stores depleted. CRP of >5 considered chronic inflammation. Must always get CRP done with ferritin to take the whole picture into account and work out if ferritin is reflective or inflammation or iron stores. Can also use ESR; if CRP normal but high clinical suspicion of infection Serum iron: can be normal or low in iron deficiency so not very reliable Total iron binding capacity/serum transferrin: high in iron deficiency (strong hold due to lack of Fe) and low in anaemia of chronic disease Transferrin saturation (TSAT): decreased in iron deficiency anaemia (<20% may respond to iron therapy) Staining shows small (microcytic) and oxygen deficient cells (light stain) OGD and colonoscopy to investigate for GI cause of unexplained iron deficiency anaemia (urgent referral) ```

Answer 38

Iron deficiency anaemia is a SIGN not diagnosis (at first): MUST RULE OUT UNDERLYING CAUSES: ``` GI Red flags: New onset indigestion New change in bowel habit Blood in stool Melaena New IBS in elderly ``` Gynaecological Menstrual history Pregnancy Urological Haematuria ``` Other Anticoagulants Telangiectasia Coeliac disease IBD **if someone has recently started anticoagulant DOAC then has life threatening or sudden increase GI bleeding it can often be an early sign of bowel cancer!!** ``` NICE referrals guide: urgent (2WW) referral 60 + with iron def. anaemia aged 50+ in those with iron def. anaemia and rectal bleeding urgent colonoscopy in 55+ YO iron def. anaemia newly diagnosed patient. refer all men and postmenopausal women with IDA unless they have overt non-GI bleeding All people 50+ with marked anaemia or significant family history of colorectal carcinoma premenopausal women if <50 YO with colonic symptoms, strong family history of GI cancer or persistent IDA despite treatment refer to gynaecology for menorrhagia unresponsive to medical management or any postmenopausal bleeding irrespective of age

Answer 39

(BNF says 3x daily 200mg) but clinical practice: Ferrous sulphate 200mg one tablet every other day/daily for 3 months (better iron absorption as only 60mg can be absorbed in 24 hours with fewer side effects) OD for anaemic patients and every other day for non-anaemic patients but iron deficient. Side effects GI upset and nausea and vomiting. Do not take with food, take separately from Ca containing foods and drinks (milk), Ca supplements, cereals, dietary fibres, tea, coffee and eggs. Antacids/PPIs may reduce absorption. Ascorbic acid tablets (or half glass orange juice) with iron enhances absorption. Not suitable for those with inflammatory conditions or malabsorption conditions (RA, IBD etc.) or those genuinely intolerant of oral iron 1g IV ferric carboxymaltose on week 1, reassess Hb then 500mg IV week 3, reassess iron stored/ferritin on week 6. Side effects rash, anaphylaxis and skin staining Follow up with underlying conditions and to assess medications (usually 1 week) **NEVER transfuse young females who are IRON DEFICIENT unless they are clinically compromised (vitals poor)/Hb <70g/L!!** Once transfused once in UK can no longer donate blood anywhere in the world Coping with side effects of iron tablets: N&V, stomach pain or heartburn: take ferrous sulfate with or just after meal or snack. Stick to simple meals no rich or spicy foods Constipation: each high fibre foods, exercise regularly, talk to pharmacist/doctor about laxative options Dark/black stool: normal and nothing to worry about. Safety net for black and sticky looking stool, red streaks in it or feel unwell in any other way

Answer 40

MCV low then also need: Serum iron level Serum ferritin: also acts as acute phase reactant protein and rises in malignancy, so is useful to assess iron storage in healthy patients but NOT sick patients Total iron binding capacity (TIBC) How to differentiate between microcytic anaemias: Iron deficiency anaemia TIBC - Increased serum iron - reduced serum ferritin - reduced Chronic inflammation/malignancy TIBC - reduced iron - reduced ferritin - normal/increased Thalassemia (alpha or beta) TIBC - normal iron - normal/increased ferritin - normal

Answer 41

Inherited blood disorder characterised by abnormal hHb production Patients have defect in either alpha or beta chain of Hb causing production of abnormal RBCs and resultant anaemia Most common in mediterranean, middle east, southern china, south/central/southeast asia Classification based on chain affected: Alpha thalassaemia: mutation in alpha globulin on chromosome 16 results in reduced alpha chain production. Carriers of condition are more common. Mostly asymptomatic no treated needed however need to be aware for genetic testing for their children who may receive homozygous Beta thalassaemia: from mutation in beta globulin on chromosome 11 reduced B chain production. Can be transfusion dependent or non transfusion dependent based on stage.

Answer 42

minor (trait): carrier state, asymptomatic or mild well tolerated with Hb >90g/l intermedia: mild symptoms if present, moderate intermittently tolerated Hb >80g/l does NOT usually need transfusions to maintain Hb major: severe and symptomatic. presents in first year of life with severe anaemia and failure to thrive extramedullary haematopoiesis: splenomegaly and skull bruising life long blood transfusions needed. iron overload can cause heart issues, pancreatic issues (diabetes) and endocrine dysfunction

Answer 43

Anaemia where bone marrow produces ringed sideroblasts (erythroblasts with iron loaded mitochondria) therefore can only be seen in bone marrow biopsy Body has enough iron but due to genetic or acquired defects is unable to incorporate the iron into RBCs leading to anaemia Can be congenital or acquired Congenital: X linked disorder, mitochondrial disorders, pearson syndrome Acquired: myelodysplastic syndrome (MDS), copper deficiency, alcohol, TB treatment, idiopathic

Answer 44

Premature destruction of RBCs Causes often overlap and can get acute and chronic forms of most causes (flare ups) Pathology: increased unconjugated bilirubin from increased breakdown of haem Broken down globins mopped up by haptoglobin by binding Measure haptoglobin levels (free unbound to RBCs) therefore decrease and become low in haemolytic anaemia Raised LDH also sign of haemolytic anaemia Increased count of reticulocytes due to needing to to replace cells faster ``` Causes: Inherited Defects of RBC membrane production: Hereditary spherocytosis Defects in haemoglobin production Thalassaemia Sickle cell anaemia Defective RC metabolism G6PD deficiency (can be triggered by drugs eg malarial) Pyruvate kinase deficiency ``` ``` Acquired: Mechanical hemolytic anaemia: Mechanical heart valves Immune causes: Mycoplasma infection Autoimmune: SLE, RA, Hodgkin’s lymphoma, Chronic lymphocytic leukaemia (CLL) ``` Autoimmune (DAT +ve) Extravascular Intravascular Non-autoimmune (DAT -ve) **Important to differentiate between auto and non-autoimmune as auto are more at risk of cancers**

Answer 45

Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells. warm AIHA due to AB that is active at normal body temperature - anti IgG cold hemagglutinin disease (CHAD) is due to ABs that cause RBC agglutination and hemolysis at temperatures below body temp (extremities) - anti C3d AB direct antiglobulin test (Coombe's test) for ABs against RBC: detects presence and strength of anti-IgG and anti-C3d to determine which autoimmune type they have Need to assess for warm or cold as treatment varies massively depending on this. Warm will respond to steroids while cold will not and needs rituximab immune suppressants instead Warm type 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 Type Autoimmune Haemolytic Anaemia: This is also called cold agglutinin disease. At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together. This is called agglutination. This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen. Cold type AIHA is often secondary to other conditions such as lymphoma, leukaemia, systemic lupus erythematosus and infections such as mycoplasma, EBV, CMV and HIV. Management of autoimmune haemolytic anaemia: Blood transfusions Prednisolone (steroids) Rituximab (a monoclonal antibody against B cells) Splenectomy

Answer 46

``` Hb low MCV high reticulocytes elevated heptoglobin decreased bilirubin increased conjugated bilirubin low LDH raised (by-product of RBC breakdown) ``` Normocytic anaemia Blood film shows schistocytes (fragments of RBCs) Direct Coombes test is positive in autoimmune cause

Answer 47

Underlying disease/chronic inflammation Increases IL-6 and other Inflam cytokines in liver Increases hepcidin production which prevents iron absorption in bowel and/or has an inhibitory effect reducing erythropoietin stimulation in bone marrow leading to decreased erythrocyte formation Important to distinguish between which pathway is occurring as to know if patient will respond to iron replacement (IV iron in absorption problems) or if they need bone marrow stimulation

Answer 48

Low platelets Liver produces thrombopoietin which regulates platelets production Travels to bone marrow and circulating TPO binds to TPO receptor which causes cells to absorb the TPO and remove it from the blood There is no direct negative feedback on the liver so always produces at a steady rate Therefore can have production problem if liver disease Or bone disease can cause problem with TPO absorption There is very little variation in platelet count in single individual (due to continuous liver production) therefore a change by 98 x10(9) should prompt investigation even if they’re still within the normal range classification: NORMAL range: 150-400 MILD: 100-149, can be managed without referral MOD: 50-99, may same day need referral if signs of active bleeding SEVERE: <50, same day referral ITP: <30, medical emergency

Answer 49

Chronic liver disease ``` Medications: Antibiotics (piperacillin, vancomycin, rifampicin,) Antiepileptics Quinine Metformin (causes vitamin B12 def.) PPI (reduced nutrient absorption) Heparin induced (HIT) Cytotoxics (chemotherapy) ``` Alcohol Nutritional deficiencies Bone marrow disorders: Leukaemia Lymphoma Myeloma Myelodysplastic syndrome Autoimmune Infections: Viral: HIV, hepatitis B/C, CMV and EBV, MMR, parvovirus

Answer 50

Viral: HIV, hepatitis B/C, CMV and EBV, MMR, parvovirus cause megakaryocyte apoptosis, platelet activation and consumption and direct TPO reduction from liver injury Acute: thrombocytopenia can resolve spontaneously after virus has cleared Chronic: HIV directly toxic to megakaryocytes causes secondary ITP. primary HIV associated thrombocytopenia (PHAT) Cytomegalovirus reactivation due to immune suppression Hepatitis B same mechanism as liver disease Bacterial: direct bone marrow suppression in severe sepsis (mycoplasma, H. pylori, tick borne infections)

Answer 51

Thrombocytopenia following exposure to heparin Rapid production of IgG antibodies with ABSENCE of IgM ABs; suggesting secondary immune response (IgG - long term memory) Anyone who goes into hospital gets put on heparin prophylaxis LMWH to avoid clotting and VTE/PE/DVT, these are considered never events in hospital so must be on anticoagulants Some people respond very badly to heparin IgG long term memory Ab suggesting overactivation of immune system triggered by heparin Doesn't really happen with fondaparinux and sometimes this can be treatment

Answer 52

Received heparin within <100 days (typically 5-10 days) Recent venous/arterial thrombosis Recent orthopaedic/CV surgery (most commonly) Absence of other cause: sepsis, medications Absence of bleeding (no/minimal petechiae/ecchymosis) + Thrombocytopenia (50% drop in platelet count - does not need to be below limit) ``` Risk assessment: 4Ts score for HIT: Degrees of thrombocytopenia Timing of platelet count fall Thrombosis or other sequelae Other causes for thrombocytopenia ```

Answer 53

Gum bleeding: active or stopped? Epistaxis: bi or unilateral? Unilateral suggests the bleed is probably small, more proximal bleed (vessel) pressure likely to stop. Bilateral suggests more distal source of bleed and likely more sinister cause Skin: petechiae/bruising? Was the bruising spontaneous or traumatic? (safeguard abuse) GI: upper or lower GI bleed signs? Upper GI: normal creatinine or raised? (breaking down muscle) CNS: new headache or seizure? Anaemia: acute or chronic?

Answer 54

Mild: 149-100 Moderate: 99-50: not bleeding actively then refer to haematology (send first line of bloods and coagulation screen). If actively bleeding signs present then same day referral with haematology Platelet count >50 then bleed probably not caused by platelets so check other coagulation factors: INR, aPTTr and fibrinogen Severe - <50; platelets are potential cause of bleeding and platelet transfusion may be indicated. Needs a same day referral for review by haematology

Answer 55

True thrombocytopenia: anisocytosis/clumping is seen MDS myelodysplastic syndrome: shows hypogranular platelets, dysplastic neutrophils and macrocytosis Acute leukaemia (AML/ALL): shows circulating peripheral blasts, auer rods/promyelocytes

Answer 56

blood film Haematinics: Iron studies: iron level, TIBCm TSat and ferritin Vitamin B12: serum +/- MMA Serum folate Liver and bone profile: LFTs: raised ALP, ALT and GGT Calcium: raised calcium can indicate malignancy ``` Virology: HIV Hepatitis B/C antigens and ABs EBV IgG, IgM CMV IgG, IgM ``` Specialist tests: Myeloma screen: serum protein electrophoresis, serum free light chains Hep2ANA (autoimmune screen): Particularly SLE autoimmune screening Always look for blood tests done previously to use as a baseline Normal for reticulocytes to increase in anaemia as this is to compensate in anaemic patients Severe decreased platelets and signs of active bleeding - super concerning In absence of active bleeding then they’re not dying but still need urgent referral

Answer 57

Isolated thrombocytopenia (without clear cause) Presents with tiny, circular non-raised patches that appear on skin or mucosal membranes <5mm (PETECHIAE) Wet petechiae seen on soft palate Purpura: tiny circular non-raised patches on skin or mucous membranes 5-9mm Mucosal bleeding from nose or gums Diagnosis of exclusion based on finding no other cause for low platelets Add in childrens management from ppt

Answer 58

Acute setting: High dose steroids (dexamethasone 40mg PO OD for 4 days OR prednisolone 1mg/kg taper off for four weeks. Problem with prednisolone is usually symptoms come back during weaning process so can be on steroids for months instead of weeks so more likely to have long term steroid effects IV Igs if steroids CI or not tolerated. Risk of transmittable disease/reaction (same as blood transfusion and can no longer ever donate blood products. Used if steroids don’t work/aren’t tolerated If platelet count is not rising within 3 days then challenge with alternative therapies or another round of same therapy Is possible after multiple therapies to lose responsiveness to treatment therefore is not good for chronic cases to receive multiple acute setting managements Patients with ITP will never have normal platelet count as long as above 30 that's good Only below 30 will they use acute treatment because of the risk of losing response to therapies Long term therapies: Azathioprine OR mycophenolate mofetil (MMF) TPO agonists (eltrombopag daily tablet or romiplostim weekly injection). Still only aiming for platelet target of 50-100 in these patients not normal amount Immunomodulatory medications like rituximab can help put people into remission for several years, need special funding for it due to expense and length of treatment Emergency: Platelet transfusion if major active bleed Patient will have destroyed all platelets given within 6-8 hours so very important to also establish acute setting management to follow up and ensure bleeding doesn’t resume

Answer 59

Medical emergency Very rare, more common in females, statin use and pregnancy Often screen for cancers as well as can be associated with some cancers Pathophysiology: Von Willebrand factor increases clot formation ADAMTS13 responsible for splitting von Willebrand factor In TTP there is an ADAMTS13 deficiency meaning there is inappropriate intravascular clot formation causing thrombosis AND thrombocytopenia Causes multi organ failure from clot formation Microtears of vessels and bleeding symptoms develop once platelets have been used up WORST OF BOTH

Answer 60

Investigation: CT exclude haemorrhagic stroke, consider ischaemic if no sign of haemorrhage Bloods Management: Immediate transfer to critical care/ICU at a TTP centre; avoid delaying for further ix unless life threatening DO NOT give platelets - causes increased clotting and more ischaemia and DO NOT transfuse TTP patients unless there is active haemorrhage/life threatening - seek haematologist 222 crash call Gain central venous access (very large bore) give daily plasma exchange (until platelets are >150 for 2 consecutive days) Immunosuppression: high dose steroids (methylprednisolone) or MMF Anticoagulation once platelets reach >50 with LMWH or aspirin

Answer 61

>10 - all patients; routine dentistry >20 - sepsis/acutely unwell (incl. T. 38+) >30 - dental extraction >50 - surgery/invasive procedure. anticoagulation of any kind >80 (>100) - ocular or neurosurgery **As long as there’s no signs of active bleeding: ALWAYS CHECK ocular/neuro guideline is 80 but clinical practice is >100 to ensure they don’t fall below 80 as once below 80 is irreversible**

Answer 62

bone marrow disease in elderly Rare group of disorders where the body no longer produces enough healthy RBCs/produces dysplastic and ineffective RBCs Can cause cytopenia, bicytopenia or pancytopenia Sometimes called bone marrow failure disorder and is a type of cancer Most patients are >65 YO and is more common in men Can range from mild-severe presentations varying on type, individual etc. May be asymptomatic in early stages or progress to fatigue and dyspnea Stem cell transplants is only curative treatment but many treatments to improve symptoms, quality of life and life expectancy In some types of MDS only one type of blood cell is affected but in other multiple can be affected Some MDS types will develop into acute myeloid leukaemia ``` Risk factors: Chemotherapy Acute lymphocytic leukaemia in childhood Hodgkin's disease Non-hodgkin lymphoma Smoking Benzene contact (in plastics, dyes, detergents etc) Down’s syndrome, fanconi anemia, bloom syndrome, ataxia telangiectasia ```

Answer 63

``` Presentation: Constant fatigue Unusual bleeding Bruising and red marks under skin Pallor Dyspnoea Macrocytic anaemia and mild thrombocytopenia that progresses ``` Diagnosis: Physical exam Blood sample: FBC, MCV, ferritin, iron studies Bone marrow biopsy/sample and genetic analysis

Answer 64

Observations and monitoring condition Chemotherapy drugs for leukaemia Immunosuppressive therapy Blood transfusions Iron chelation to reduce excess mineral Growth factors to encourage natural bone marrow erythropoiesis Stem cell transplant is only curative treatment

Answer 65

Group of blood cancers which are characterised by accumulation of malignant WBCs in bone marrow often spill out into peripheral blood Acute leukaemia: aggressive forms. Damage to immature (blasts) WBCs either the haematopoietic stem cells itself or one of it’s early progenitors. Often present with patients acutely unwell. 4 main types: All Cell Mates have Common Ambitions AML: acute myeloid leukaemia ALL: acute lymphoblastic leukaemia CLL: chronic lymphoblastic leukaemia CML: chronic myeloid leukaemia Pathology: 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) and platelets (thrombocytopenia).

Answer 66

Acute myeloid leukaemia is the most common acute leukaemia in adults. There are many different types of acute myeloid leukaemia all with slightly different cytogenetic differences and differences in presentation. It can present at any age but normally presents from middle age onwards. It can be the result of a transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis. A blood film will show a high proportion of blast cells. These blast cells can have rods inside their cytoplasm that are named Auer rods.

Answer 67

pancytopenia (anaemia, thrombocytopenia and leucopenia) anaemia: SOB, fatigue, palpitations, chest pain, paraesthesia thrombocytopenia: petechaie, purpuric rash, easy bruising, bleeding leucopenia: recurrent infections, sepsis, very low WCC OR really high WCC from machine misreading blasts as mature WCs ``` Most common symptoms in the lead up to diagnosis: seeing more than one of these in same patient think of FBC investigations to look for decreasing no. of cells and look into underlying cause before they present septic into A+E : fatigue fever bruising or bleeding repeated infections feeling weak or SOB joint or bone pain ```

Answer 68

FBC: cytopenias (reduction in one of 3 cell lines eg low Hb) or pancytopenia (reduction in all 3 cell lines) - anaemia, thrombocytopenia and neutropenia Blood film: circulating peripheral blasts Biochemistry: elevated LDH (increased RBC breakdown) +/- elevated uric acid diagnosis: Pancytopenia with circulating peripheral blasts Myeloid or lymphoid blasts? Morphology of cells will determine between myeloid or lymphoid auer rods are ONLY seen in AML (super tiny purple line) Also look at CD markers using flow cytometry Diagnosis confirmed only with bone marrow biopsy (aspirate and trephine (BMAT): Bone marrow blasts >20%: normal bone marrow blasts % is 1-2% Can be diagnosed with blasts <20% IF cytogenetic or molecular genetic abnormalities are present.

Answer 69

Induction treatment: Aim to reduce cell burden with chemotherapy; can be curative or life prolonging. Complete remission = <5% blasts in bone marrow, normal blood counts Consolidation treatment: Once remission achieved aim to maintain absence: chemo if BMAT <5% blast cells (high dose cytarabine) OR if >5% blast cells re-induction chemotherapy +/- intensification HSCT for poor risk cytogenetics; aim for stem cell transplant once in complete remission Haematopotic stem cell transplant: Patients with intermediate or poor risk cytogenetics or relapsed disease Significant morbidity and mortality associated with stem cell replacement so is last resort management Allogeneic HSCT = someone else’s stem cells given to the patient Supportive care: Packed RBCs: target Hb >70 (unwell), >80 (well), >90 (symptomatic patients) Platelets: target >10 (all), >20 (unwell/sepsis), >50 (for anticoagulation), >100 (for brain haemorrhage) Prophylactics: antivirals (aciclovir 400mg PO BD), antifungals (posaconazole 300mg PO OD), antibacterial (neutrophil <1 ciprofloxacin 500mg PO BD; neutrophils >1 none needed) Do not stop prophylaxis unless haematologist has been consulted

Answer 70

Blood cancer of children (ALL children get ALL) Cancer of lymphoid WBCs Single lymphoblast undergoes genetic changes which prohibit differentiation coupled with mutations affecting cellular proliferation Most common form of acute leukaemia in children typically presents at ages 3-7, then >40 YO 90% cure rate Want to avoid LP for diagnosis due to risk of bleed (low platelet count), also very small risk of giving the patient CNS leukaemia (very difficult to treat and pushed from vessel to CNS) LP must only be done by haematologists (they administer chemo into the spinal cord after LP!!) Acute lymphoblastic leukaemia is where there is malignant change in one of the lymphocyte precursor cells. It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia. This is the most common cancer in children and peaks around 2-4 years. It can also affect adults over 45. It is often associated with Downs syndrome. Blood film shows blast cells. It is associated with the Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL.

Answer 71

Blood film: Immunophenotype seen by flow cytometry (which cell surface receptors are present) Cytogenetic gene mutations on philadelphia chromosome = poor prognosis must differentiate from acute lymphoblastic lymphoma which has lymph node involvement or extra nodal masses and has worse prognosis

Answer 72

Myeloproliferative neoplasm (MPN) characterised by dysregulated production and uncontrolled proliferation of mature and granulocytes (neutrophil, basophil, eosinophil) with fairly normal cellular differentiation Presentation: 20-50% asymptomatic and picked up on routine blood tests Fatigue Malaise Weight loss Excessive swelling Abdominal pain: Splenomegaly, Hepatomegaly (from taking up role of making WBCs as bone marrow is not doing the job)

Answer 73

Investigations: WCC: 90-100 Blood film: predominantly neutrophils (myelocytes) and low level peripheral blasts <2% Philadelphia chromosome: BCR-ABL mutation translocation between chromosomes 9 and 22 associated with CML, take tablet OD for life and same life expectancy as everyone else Management: TKIs e.g. imatinib Hydroxycarbamide

Answer 74

Mature B cell neoplasm characterised by progressive accumulation of monoclonal B lymphocytes ``` Presentation: Elderly patient Often detected on routine test for something else; autoimmune haemolytic anaemia (AIHA) or hypogammaglobulinemia Low level LAP Splenomegaly Hepatomegaly ```

Answer 75

Diagnosis: If well; repeat FBC in 2-3 months time to reassess lymphocyte count Investigate lymphocytosis in mean time (HIV, HBV, HCV, EBV) Refer to haematology if repeat lymphocyte count is raised or severe infection/anaemia present Don’t usually need treatment Watch and wait, often die WITH CLL however not FROM CLL Prognosis still roughly the same even with later presentation however treatment cannot reverse damaged done in symptomatic patients (hyperviscosity can cause blindness or other systemic symptoms)

Answer 76

Blood cancers characterised by accumulation of malignant lymphocytes in lymph nodes and lymphoid tissues, classically presenting with LAP types: hodgkin lymphoma: classical (nodular scleorsis, mixed cellularity, lymphocyte rich, lymphocyte depleted) or nodular lymphocyte-Predominant Non-hodgkin's lymphoma: high grade - diffuse large B cell lymphoma (mantle cell lymphoma, peripheral T cell lymphoma, angioimmunoblastic lymphoma, Burkitt's lymphoma) or low grade - follicular lymphoma High grade lymphoma will always need treatment will die because of if untreated Low grade lymphomas can be present asymptomatically with no problems often need no treatment just need lifelong monitoring in case it develops into high grade lymphoma

Answer 77

Blood cancer that arises from the germinal centre or pot germinal centre, B lymphocytes Formed of minority of malignant cells that are surrounded by an inflammatory background of cells Primary lymphoid organs: bone marrow and thymus. Secondary lymphoid organs: lymph nodes, spleen (germinal centre) 10% of all lymphomas, patients are usually young (20 YO) slightly more common in men ``` Types: Nodular sclerosis Mixed cellularity Lymphocyte rich Lymphocyte depleted Nodular lymphocyte predominant ``` Pathophysiology Classical Reed-Sternberg cells on a background of inflammatory cells (lymphocytes, eosinophils, neutrophils, macrophages, plasma cells, fibroblasts) Often associated with collagen deposition and fibrosis Reed-sternberg cells: biobed, double or multiple nuclei, two or more prominent, eosinophilic, inclusion like nuclei

Answer 78

Painless LAP: cervical or supraclavicular, non tender, rubber consistency Non productive cough/gradually worsening SOB: mediastinal mass B symptoms: night sweats (drenching 3+ x weekly), weight loss, fevers Pruritus months or years prior to diagnosis Fevers in absence of infection diagnosis Clinical symptoms and tissue biopsy (excisional biopsy) Cannot use FNA as may miss diagnosis/miss malignant cells, need much larger samples Routine light microscopy and immunophenotype with immunohistochemistry PETCT scan for staging

Answer 79

stage 1: lymphoma in single lymph node or one group of lymph nodes or an organ of the lymphatic system (such as the thymus) stage 2: lymphoma is in two or more groups of lymph nodes, on same side of the diaphragm stage 3: lymphoma on both sides of the diaphragm stage 4: lymphoma is in an extra nodal site and lymph nodes are affected above and below diaphragm or is in more than one extra nodal site Most patients present at stage 3 or 4 Stage 4 most common presentation and survival rate is 85% so prognosis is very good. Curative often, don’t shove them onto palliative care

Answer 80

stage 1/2 disease: ABVD - doxorubicin, bleomycin, vinblastine and dacarbazine +/- intense field radiotherapy stage 3/4: escalated BEACOPP. bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone. higher rates of toxicity including reversible bone marrow suppression, secondary malignancies, sterility and rare cases of fatal sepsis relapsed/refractory disease: brentuximab ICE: ifosfamide, carboplatin and etoposide GDP: gemcitabine, dexamethasone, cisplatin once/if in remission - aim to autologous stem cell transplant prognosis: 80% 10 year survival rate, better in <40 YO and female very few people have relapses or need stem cell transplants

Answer 81

Blood cancer arising from B or T lymphocytes 80% of all lymphomas Predominantly in later life >70 Slightly more common in men Types: High grade: diffuse large B cell, burkitt lymphoma, angioimmunoblastic lymphoma. These are fast growing, have acute presentation onset with rapid deterioration and will always need treatment Low grade: follicular or splenic marginal zone lymphoma. Indolent, often use watch and wait management

Answer 82

Painless LAP: cervical, axillary or inguinal, non tender, rubber consistency, rapidly growing Abdominal symptoms: abdominal LAP, abdominal pains/change in bowel habit B symptoms: night sweats (drenching 3x weekly), weight loss, fevers without infection *if you feel cervical enlarged lymph nodes MUST check armpits and inguinal lymph nodes in absence of systemic illness should not all be enlarged* Diagnosis: Clinical symptoms and URGENT tissue biopsy to confirm LAP show significant enlargement, persist for more than 4-6 weeks with progressive increase in size Light microscopy and immunophenotype with immunohistochemistry PETCT for staging

Answer 83

high grade: Chemotherapy low grade: (follicular lymphoma) watch and wait radiotherapy

Answer 84

Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma

Answer 85

Premalignant clonal plasma cell disorder Presence of monoclonal protein (M protein or paraprotein) With NO evidence of multiple myeloma, amyloidosis or Waldenstrom macroglobulinemia (WM) Investigations: Presents to GP with nonspecific symptoms Back pain SOB Raised globulin noticed on routine bloods and requests serum protein electrophoresis (SPEP), serum free light chains (SFLC) and paraprotein quantitation (PP) Urine symptoms indicate end organ failure

Answer 86

M protein <30 g/l Bone marrow clonal plasma cells <10% and low level of plasma cell infiltration in a trephine biopsy No myeloma related organ or tissue impairment (ROTI) Calcium levels increased: corrected serum Ca >0.25mmol/l above upper limit of normal or >2.75mmol/l Renal insufficiency attributable to myeloma Anaemia: Hb 20g/l below the lower limit of normal or Hb <100g/l Bone lesions: lytic lesions or osteoporosis with compression fractures (MRI or CT scan)

Answer 87

Malignant blood cancer of plasma cells leading to: CRAB symptoms. Calcium, renal failure, anaemia and bone pain as well as cytopenias (pancytopenia: anaemia, thrombocytopenia and neutropenia) Multiple myeloma is terminal diagnosis however chemotherapy can prolong life. Causes may bony metastases which severely disables individual and leads to death Paraprotein quantitation will be >30 OR presence of CRAB symptoms Ix: Raised globulin noticed on routine bloods and requests serum protein electrophoresis (SPEP), serum free light chains (SFLC) and paraprotein quantitation (PP) Urine symptoms indicate end organ failure

Answer 88

chemotherapy radiotherapy autologous stem cell transplant (auto-HSCT): aim upfront chemotherapy followed by transplant followed by close observation and chemotherapy when relapses occur

Answer 89

``` MGUS: - monoclonal paraprotein <30 - no renal issues - no anaemia - no calcium issues - no bony lesions needs annual monitoring FBC, renal profile, bone profile and history ``` myeloma: - monoclonal paraprotein present - renal impairment - anaemia (hb <100) - Hypercalcaemia - bony lesions

Answer 90

``` Polycythaemia vera (PV) Essential thrombocythemia (ET) Chronic myeloid leukaemia (CML) Primary myelofibrosis (MF) Chronic neutrophilic leukaemia (CNL) Chronic eosinophilic leukaemia (CEL) ```

Answer 91

Elevation of red cell mass (RCM), part of blood occupied by RBCs Detected by abnormal elevation of Hb and/or haematocrit (Hct)/packed cell volume (PCV) Hb and Hct are concentrations of components of peripheral blood rather than absolute numbers types/cause: - Relative: just due to reduced plasma volume is normal physiological response will self correct - absolute: primary or secondary Regulation of RBC: Blood loss stimulates RBC production detected by hypoxia in kidneys stimulating EPO production and subsequent erythropoiesis Renal cell carcinomas can increase EPO resulting in too much RBC production CNS tumours can also cause increased erythropoiesis Hepatocellular carcinoma can also make too much EPO and RBCs

Answer 92

Hypoxia: pO2, carboxyhemoglobin % (3-4% = smoker; any higher ask to have their boiler checked), sleep studies, smoking history, CXR Renal cell carcinoma, stenosis or adrenal carcinoma: renal bloods (creatinine, urea, K+, U+Es, eGFR), urine dip (haematuria), urological history, USS abdomen/renal tract Hepatic (HCC): liver bloods (ALT, ALP, GGT) and alcohol history Neurological (hemangioblastoma): headaches, changes in behaviour, nausea and vomiting - MRI of head (diagnosis of brain tumour) *eGFR only to be used in primary/non-acute setting as takes awhile to show acute changes*

Answer 93

Clonal proliferation of myeloid cells, with variable maturity and hematopoietic efficiency, resulting in raised red cell mass Intrinsic defect within the bone marrow JAK-STAT signalling pathway (JAK2 V617F exon 14 mutation) JAK2 activates EPO, GSCF and TPO downstream regulation Mutation makes haematopoietic stem cells more sensitive to growth factors causing increased proliferation (of potentially all 3 cell lines) presentation Raised Hb and Hct/PCV Associated with iron deficiency (using up the iron so not enough present) Reduced EPO level is very suggestive (body trying to stop EPO due to increased sensitivity however symptoms still persist as EPO sensitivity so increased) Erythromelalgia (burning pain in hands and feet) Pruritus +/- skin excoriation from scratching Facial plethora (red face) Gouty arthritis and tophi from increased RBC destruction increased uric acid = gout Thrombocytosis (platelet >450) Leukocytosis (>11.0)

Answer 94

``` Raised platelet count (>450,000 microL) Normal between 150-400 Primary (haematological) Or secondary (reactive) Secondary reactive causes: Acute blood loss: increased proliferation of progenitor cells ``` Iron deficiency: megakaryocytic erythroid progenitor cells increased Acute haemolytic anaemia: increased proliferation of progenitor cells and increased cytokine release Infections: acute and chronic infectious TB Inflammatory: RA, IBD, nephrotic syndrome Tissue damage: MI, acute pancreatitis, severe trauma, burns, post-surgical Ovarian cancer: IL-6 producing cancers increase TPO production ``` Lung cancers Colorectal cancers Prostate cancers Breast cancers *always screen patients with isolated raised platelet count for cancers* ``` Investigation: TPO, IL-11 and IL-6 inflammatory markers all increase with thrombocytosis Management: Treating underlying cause

Answer 95

Clonal stem cell disorder resulting in excessive platelet production Causes: JAK2 V617F mutation (65%) causes haematopoietic SCs more sensitive to growth factors CALR mutation (25%) leads to cytokine independent growth and activation of JAK/STAT signalling. Mutated CARL interacts with MPL and activates MPL directly MPL mutation (5%): encodes for TPO receptor mutation and activates TPO-R

Answer 96

Around 50% asymptomatic just incidental finding on routine tests ``` Vasomotor symptoms (microvascular disturbances) Headache Lightheadedness Syncope Atypical chest pain Livedo reticularis Transient visual disturbances ``` ``` Thrombotic/hemorrhagic event CVA MI SVT DVT PE ``` First trimester pregnancy loss management: Hydroxyurea and aspirin for primary thrombocythemia and high risk of blood clots

Answer 97

Stage 1 is remission induction. The aim of remission induction is to kill the leukaemia cells in your bone marrow, restore the balance of cells in your blood, and relieve your symptoms. Involves regular blood transfusions and antibiotic prophylaxis alongside chemotherapy, steroid therapy and other targeted therapies Stage 2 is consolidation. This aims to kill any remaining leukaemia cells. Regular chemotherapy injections Stage 3 is maintenance. This involves taking regular doses of chemotherapy medicines to stop leukaemia coming back, can last for around 2 years

Answer 98

ALL CeLL mates have CoMmon AMbitions <5 and >45 - acute lymphoblastic leukaemia (ALL) >55 - chronic lymphocytic leukaemia (CLL) >65 -chronic myeloid leukaemia (CML) >75 acute myeloid leukaemia (AML) Summary to differentiate: Acute lymphoblastic leukaemia: Most common leukaemia in children. Associated with Down syndrome. Chronic lymphocytic leukaemia: Most common leukaemia in adults overall. Associated with warm haemolytic anaemia, Richter’s transformation into lymphoma and smudge / smear cells. Chronic myeloid leukaemia: Has three phases including a 5 year “asymptomatic chronic phase”. Associated with the Philadelphia chromosome. Acute myeloid leukaemia: Most common acute adult leukaemia. It can be the result of a transformation from a myeloproliferative disorder. Associated with Auer rods.

Answer 99

``` FBC initial Ix within 48 hours if leukaemia is suspected Blood film Lactate dehydrogenase (LDH) often raised but non-specific Bone marrow biopsy CXR for infection/LAP Lymph node biopsy to assess for lymphoma LP if CNS involvement CT, MRI, PET scan for staging ```

Answer 100

``` The most common inherited cause of abnormal bleeding (haemophilia) Many genetic causes most are autosomal dominant Causes involve a deficiency, absence or malfunctioning of the glycoprotein von Willebrand factor (VWF). Three types (1-3) ranging in severity, type 3 being the most severe ``` ``` Presentation: Easy, prolonged or heavy bleeding Bleeding gums with brushing teeth Epistaxis Menorrhagia Heavy bleeding with injury, surgery Family history ```

Answer 101

Diagnosis: Clinical history Family history Bleeding assessments: coagulation status and bloods Management: Does not need day to day management; only needed in response to a major bleed or trauma to stop the bleeding or in preparation for operations to prevent bleeding Desmopressin stimulates release of VWF VWF can be infused Factor VIII often infused with plasma derived VWF to help coagulation Women with menorrhagia can try a combination of: tranexamic acid, mefenamic acid, norethisterone, COC, mirena coil. Hysterectomy may be needed in severe cases

Answer 102

Inherited severe bleeding disorders Haemophilia A is caused by a deficiency in factor VIII Haemophilia B (Christmas disease) is caused by a deficiency in factor IX, tends to be less severe They are X linked recessive disorders, in order to have the condition you must have an X chromosome with the abnormal gene (must be homozygous in women but only heterozygous in men due to only one X chromosome) Women can be carriers of the disease while men are almost exclusively affected due to only needing one recessive gene

Answer 103

Bleed excessively in response to minor trauma Spontaneous haemorrhage Often present in neonates or early childhood Can present in infants with intracranial haemorrhage, haematomas and cord bleeding Haemarthrosis (bleeding in joints) - mostly in haemophilia A Bleeding in muscles Bleeding in gums, GIT, retroperitoneal space, following procedures - mostly from haemophilia A Haematuria

Answer 104

Diagnosis: Bleeding scores Coagulation factor assays: in female carriers of haemophilia A you are likely to see prolonged APTT with normal PT and normal fibrinogen Genetic testing Management: Specialist haematology referral Clotting factors XII or IX can be replaced via IV infusions Can be done prophylactically or in response to bleeding Complication of this is formation of antibodies again the clotting factor resulting in treatment becoming ineffective Acute episodes of bleeding or prevention of excessive bleeding during surgery involve: infusions of clotting factor, desmopressin to stimulate VWF and antifibrinolytics like tranexamic acid

Answer 105

AKA plasma thromboplastin antecedent deficiency or Rosenthal syndrome, is a clotting disorder is a deficiency in factor XI Most commonly seen in Ashkenazi jewish populations Factor XI is important for producing thrombin protein that converts fibrinogen to fibrin during the clotting cascade Autosomal recessive disorder ``` Presentation: Easy, prolonged or heavy bleeding Bleeding gums with brushing teeth Epistaxis Menorrhagia Heavy bleeding with injury, surgery Family history ```

Answer 106

Diagnosis: Genetic testing in pregnancy Clotting tests Antibodies against XI to assess risk for developing defence against treatment Management: Tend to be treated on presentation of bleed rather than prophylaxis Can inject plasma factor XI Infusions of fresh frozen plasma PRN in operations or after traumas Fibrin glue to treat injuries Tranexamic acid (oral, IV or topical) Women with menorrhagia can consider mirena coil or COC People with severe disorder should NOT use NSAIDs as this increases bleed risk

Answer 107

X linked autosomal recessive disorder so mostly affects males while females are often carriers of the disorder Genetic abnormality that results in a deficiency of G6PD (glucose-6-phosphate dehydrogenase) in the blood It is responsible for keeping RBCs healthy and without enough the RBCs breakdown prematurely (increased haemolysis) eventually leading to haemolytic anaemia Haemolytic anaemia can be induced in those with the disorder by eating fava beans, certain legumes, infections or drugs (antimalarials, sulfonamides, aspirin and NSAIDs) Most prevalent in Africa (up to 20% population) ``` Risk factors: Male African Middle eastern Family history ```

Answer 108

Presentation: Mostly asymptomatic When triggered shows symptoms of haemolytic anaemia: tachycardia, dyspnea, dark yellow/orange urine, fever, fatigue, dizziness, pallor, jaundice of skin and eyes Once cause (infection, medications, foods etc.) has been removed then symptoms tend to resolve Diagnosis: Blood tests for G6PD, FBC, serum Hb and reticulocyte count Management: Avoid triggering foods, medications and prevent infection where possible Prompt treatment of infections Haemolytic anaemia: oxygen, blood transfusions likely to be needed

Answer 109

Disorder characterised by antiphospholipid antibodies where the blood becomes prone to clotting The patient is in a hypercoagulable state Main associations are with thrombosis and pregnancy, particularly recurrent miscarriage Can occur in isolation (primary) or secondary to an autoimmune condition, particularly SLE Associated with AP antibodies: lupus anticoagulant, anticardiolipin and anti-B2 glycoprotein I antibodies These antibodies interfere with coagulation and create a hypercoagulable state Complications/presentation: Venous thrombosis (DVT, PE) Arterial thrombosis (stroke, MI, renal thrombosis) Pregnancy complications (recurrent miscarriage, stillbirth, preeclampsia) Livedo reticularis: purple lace like rash giving mottled appearance to skin Libman-sacks endocarditis: non-bacterial endocarditis with vegetations on valves of heart. Mitral valve most often affected. Thrombocytopenia ``` Diagnosis: History of thrombosis or pregnancy complication plus persistent antibodies Lupus anticoagulant Anticardiolipin antibodies Anti-beta-2 glycoprotein I antibodies ``` Management: Referral to rheumatology, haematology and obstetrics (if pregnant) Long term warfarin with INR 2-3 to prevent thrombosis (3-4 INR with recurrent thrombosis)

Answer 110

Iron storage disorder resulting in excessive total body iron and deposition of iron in tissues The human haemochromatosis protein HFE gene is often mutated causing this condition (autosomal recessive mutation) Presentation: Usually present after age 40 when iron overload becomes symptomatic Presents later in females due to menstruation acting to eliminate iron from the body Fatigue Joint pain Pigmentation (bronze or slate grey) Hair loss Erectile dysfunction Amenorrhea Cognitive symptoms (memory and mood disturbance) ``` Diagnosis: Serum ferritin Iron studies - transferrin saturation Genetic testing (GOLD STANDARD) Liver biopsy (perl’s stain) to establish iron in parenchymal cells CT abdomen MRI ``` Complications: Type 1 Diabetes (iron affects the functioning of the pancreas) Liver Cirrhosis Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility) Cardiomyopathy (iron deposits in the heart) Hepatocellular Carcinoma Hypothyroidism (iron deposits in the thyroid) Chrondocalcinosis / psedogout (calcium deposits in joints) causing arthritis Management: Venesection (weekly removal of blood to decrease total iron) Monitor serum ferritin Avoid alcohol Genetic counselling Monitoring and treatment of complications

Answer 111

Dependent on cause; hereditary spherocytosis (most common type) treated with folate supplements and splenectomy (+ cholecystectomy if gallstones are a problem) Autoimmune haemolytic anaemia treated by blood transfusions, prednisolone, rituximab and splenectomy Prosthetic valve haemolysis treated with monitoring, oral iron, blood transfusions (severe) or revision surgery (severe)

Answer 112

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. Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation. Iron overload in thalassaemia causes effects similar to haemochromatosis: ``` Fatigue Liver cirrhosis Infertility and impotence Heart failure Arthritis Diabetes Osteoporosis and joint pain ```

Answer 113

Alpha thalassaemia: more commonly carriers of condition, asymptomatic and no treatment however need to be aware of genetic testing of children who may be homozygous. Must monitor FBC and complications. Blood tranfusion PRN, splenectomy, bone marrow transplant can be curative Beta thalassaemia: Can be transfusion or non-transfusion dependent based on stage Minor: FBC monitoring Intermedia: monitoring FBC, transfusions PRN, iron chelation to prevent iron overload Major: regular transfusions, iron chelation and splenectomy, bone marrow transplant can be curative (potentially)

Haematology Flashcards

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