haematology Flashcards

Question

what is the difference between the group and save and crossmatch tests

Answer 1

group and save - is the sample processing that determines the patient blood group (ABO and RhD) and screens for any atypical antibodies. The process takes around 40 minutes and no blood is issued crossmatch - is the final step of pretransfusion compatibility testing, to request blood from the laboratory. Crossmatching involves physically mixing of patient’s blood with the donor’s blood, in order to see if any immune reaction occurs After ensuring that donnor blood is compatible, the donor blood is issued and can be transfused to the patient. This process takes around 40 minutes, in addition to the 40 minutes required to G&S the blood.

Answer 2

type O D negative

Answer 3

1 - identify patient 2 - complete minimum indentification requiements on blood form 3- Take the blood sample and immediately after hand-write on the tube unless using a computer prepared label generated by an electronic bar-coding system. If electronic systems are used the bar-coded label must be printed at the bedside from the patients ID band. Re-check that the details on the sample tube and request form match before putting them in the transport bag

Answer 4

the person taking the sample

Answer 5

date time signature

Answer 6

OD negative - emergency immediate 5 mins group compatible blood - 10-15 mins fully crossmatched blood - 30-40 mins (maybe hours if antibody found)

Answer 7

a secondary confirmatory blood group sample - as long as it doesn't impede on delivery of urgent blood components

Answer 8

35 days 2-6 degrees alarmed fridge transfused within 4 hours of removal from fridge if removed and not transfused sent back to lab with the length of time it was out to see if it can be reused

Answer 9

20-24 degrees not in fridge as they aggregate 5-7days if removed and not used returned to lab

Answer 10

-25 degrees - 3 years transfused as soon as possible if unused return to lab

Answer 11

ensure patient has identification band in situ check minimum patient identification data set ensure informed consent IV access? pre-tranfusion obs taken within 60 mins of the transfusion only collect one unit at a time only pass over the blood to the person who requested it Clinical staff are required to check the correct component is received upon delivery, and to sign and time receipt.

Answer 12

inform the lab so they can replace it

Answer 13

- blood integrity eg no clots, leaks, damage, discoloration, expirary etc - informed consent documented - positive patient identification - check unit tag against unit label, prescription, patient ID band and PPID - perform obs - temp, pulse, resp, bp

Answer 14

central line normally | when using this the blood should be warmed through a blood warming device

Answer 15

must be a CE-marked tranfusion set with an integral mesh filter to remove microaggregates do not prime with 0.9 saline do not administer meds or other IV fluids through the access for the tranfusion as there is a risk of incompatibility (e.g. dextrose & calcium containing solutions can cause haemolysis or lead to clotting of the transfusion components the administration set should be changed every 12 hours never use the same admin set for platelets as red cells as will cause aggregation

Answer 16

- full patient identification data set with patient and on the laboratory generated label attached to the blood component against the patient's identity band - check the laboratory generated label attached to the blood component against the label affixed to the unit to ensure all the following is the same: - donation number - patients blood group - component type

Answer 17

NO WRISTBAND NO TRANSFUSION in the unconscious/compromised patient (e.g. neonates or paediatric practice or confused patients) it is imperative that greater vigilance should be taken to identify these patients, unidentified patients in A&E should use unique identification number and gender

Answer 18

sign the transfusion documentation record the donation number complete traceability documentation

Answer 19

prothrombin comples concentrate

Answer 20

patients should be transfused in an area where they can observed - advise pt on signs symps to look out for - stop transfusion immediately following any sign - check the blood component against the wrist band - antipyretic or antihistamine may be required

Answer 21

yes after 30 mins if the patient has responded to symptomatic treatment

Answer 22

- stop transfusion - check compatibility of unit - assess patient - ABCDE -Replace the administration set and preserve IV access with normal saline to maintain systolic BP Check urine for signs of haemoglobinuria Commence appropriate treatment Maintain airway and give high flow Oxygen. If appropriate administer adrenaline and/or diuretic and resuscitate if/as required. Reassess patient and treat appropriately - Seek expert advice if patient's condition continues to deteriorate document it as adverse event

Answer 23

rare usually seen in patients who have developed red cell antibodies in the past from transfusion or pregnancy. A combination of the features occurs days after the transfusion, suggesting that the red cells are being destroyed abnormally quickly signs/sympts - fever - falling haemoglobin or a rise less than expected - jaundice - haemoglobinuria

Answer 24

temp bp hr rr

Answer 25

sometimes can have autologous transfusion - recycling your own blood allogenic - drug therapies eg oral or IV iron, erythropoietin and tranexamic acid

Answer 26

only when a transfusion is likely to be required

Answer 27

group AB | has no anti-A or anti-B antibodies in it

Answer 28

85% rhesus pos | 15% neg

Answer 29

470mLs of whole blood three times a year

Answer 30

red cells in additive solution - contains up to 20 mLs of plasma leucocyte-depleted haematocrit typically 0.55 stored for up to 5 weeks at 4 degrees +/- 2 degrees can be irradiated +/or CMV neg

Answer 31

improve oxygenation to tissues by increasing circulating red cell mass main indications = - bleeding - anaemia - haemoglobin disorders - loss of 30-40% volume - if hb is below 70g/L in fit pt - if below 80-90 g/L in pt with CVS

Answer 32

for 4mL/kg of red cells = rise of 10g/L of Hb this works for people with body weights of 70-80kg if very low then use smaller volumes

Answer 33

a single donor

Answer 34

whole blood derived - 4 donations

Answer 35

20x10(9)/L

Answer 36

to prevent bleeding not stop it when platelet count drops below 10x10(9) for example in: - Reversible bone marrow failure including allogeneic stem cell transplant and critical illness - Chronic bone marrow failure if patient is receiving intensive treatment or to prevent persistent bleeding - to prevent bleeding prior to a procedure - thrombocytopenia dont have to cross match but preferre

Answer 37

yes as a first choice | fine tho as long as its 'low-titre' and another group

Answer 38

inherited coagulation factor deficiency where no suitable factor concentrate is available, e.g. Factor V deficiency Acute disseminated intravascular coagulation (with evidence of bleeding) Thrombotic thrombocytopenic purpura (TTP) Major haemorrhage* Prophylaxis before surgery (or another invasive procedure) if abnormal coagulation test results AND one or more additional risk factors for bleeding: i) Personal or family history of abnormal bleeding ii) Procedure associated with major blood loss iii) Procedure involves critical tissues such as eye, brain or spinal cord iv) Concurrent thrombocytopenia.

Answer 39

- proph - 15ml/kg | - major - 15-20ml/kg

Answer 40

As a plasma expander to correct hypovolaemia. For the reversal of warfarin anticoagulation, treatment of bleeding in this circumstance is vitamin K, with or without prothrombin complex concentrate. To non-bleeding patients with liver disease* To critically ill patients with prolonged PT or APPT in the absence of bleeding. For patients with liver disease: there is no evidence that prophylactic FFP reduces the risk of bleeding from percutaneous liver biopsy or variceal haemorrhage.

Answer 41

2 x 5-donor pools

Answer 42

- loss of one blood volume within a 24 hour period - 50% blood volume loss within 3 hours - rate of loss of 150mLs/min Bleeding which leads to a heart rate of >110 bpm and/ or a systolic BP < 90 mm Hg is a useful indicator of major blood loss of 1000 mL or more in an adult.

Answer 43

GI haemorrhage]trauma ruptured AA obstetric haemorrhage

Answer 44

Activate major haemorrhage protocol Administer high flow oxygen Insert 2 wide bore peripheral cannulae and provide fluid resuscitation. Contact key personnel, including experts to treat bleeding cause. Arrest bleeding and treat underlying cause as soon as possible. Request laboratory investigations and perform Point of Care Tests where available, including blood gas analysis and viscoelastic tests (ROTEM/ TEG). Transfuse red cells to maintain a haemoglobin level of 70-90 g/L Administer tranexamic acid within 3 hours of onset of haemorrhage unless complicated by disseminated intravascular coagulation Transfuse FFP empirically if estimated blood loss greater than 20% blood volume or if microvascular bleeding Anticipate the need for additional blood components (including red cells, FFP, platelets and cryoprecipitate) Use cell salvage where available and appropriate When bleeding is under control additional doses of FFP should be based on results

Answer 45

Give group O D negative uncrossmatched red cells in cases of life-threatening bleeding, until patient's ABO group and D status is known. The clinical assessment of the urgency of the transfusion needs of the patient is key to ensure blood availability specifically meets the needs of patient Cross-matched red cells can be transfused if already prepared for patient concerned Group specific red cells should be requested on the group and screen sample, since a full cross match will take time for serological testing. A blood warmer with rapid infusion facility should be used to reduce the risk of hypothermia. Consider use of cell salvage , where available, to reduce requirement for allogenic red cells The patient's haemoglobin level should be checked regularly (minimum of hourly intervals during active bleeding) to monitor transfusion therapy and to avoid excessive red cell transfusion. A blood gas analyser or other point of care test eg haemocue may be used. Similarly coagulation tests/ POCT should be regularly repeated. Administer 10% calcium gluconate if ionised calcium less than 1.13 mmol/l to optimise coagulation.

Answer 46

``` thrombocytopenia hypothermia hypocalcaemia hyperkalaemia adult resp distress syndrome coagulopathy ```

Answer 47

95% albumin and electrolytes but no clotting factirs or BG antibodies - so crossmatching not required

Answer 48

4.5-5% - 400mLs 5-15mLs/min | 20-25% - 100mLs 1-2 mLs/min

Answer 49

restore plasma volume in pts with interstitial oedema acute lung injury with severe resp failure promote diuresis in patients with severe hypoalbuminaemia eg hepatic cirrhosis vital signs should be closely monitored due to risk of circ overload

Answer 50

conc of three or four inactivated clotting factors - II, IX, X or II, VII, IX, X and Protein S and C anticoagulant factors treats - bleeding, peri-op proph of bleeding

Answer 51

fever muscle pain headaches these can be resolved by slowing rate of infusion and administering paracetamol

Answer 52

The total dose per course must not exceed 2g / kg body weight, usually administered over 2-5 days.

Answer 53

are adverse reactions occurring at any time up to 24 hours after a transfusion of blood or blood components

Answer 54

defined as a fever and other signs of haemolysis more than 24 hours after confirmed by - fall in Hb or failure of increment - raise in bilirubin and LDH - incompatible crossmatch not detectable pre-transfusion - iron overload

Answer 55

polycythaemia rubra vera - red cell proliferation chronic myeloid leukaemia - white cell proliferation essential thrombocythaemia - platelet proliferation myelofibrosis - marrow stroma proliferation

Answer 56

spont bleeding <20 | haemostatic >80

Answer 57

Failure of platelet production - Vitamin B12 or folate deficiency - Bone marrow infiltration (leukaemia or metastases) - Radiation, cytotoxic therapy Increased consumption of platelets - Immune thrombocytopenia (ITP) - Disseminated intravascular coagulation (DIC) - HIV infection Hypersplenism

Answer 58

Secondary Bleeding, Infection, Inflammation, malignancy Primary: Essential Thrombocythaemia - Uncontrolled malignant proliferation of megakaryocytes - Platelets >600 persistently - Arterial and venous thrombosis - Bleeding with very high counts eg >1500 - Treatment with aspirin, hydroxycarbamide, anagrelide, interferon

Answer 59

Localized vasoconstriction at the site of injury Adhesion of platelets to damaged vessel wall and formation of a platelet aggregate or plug Activation of the coagulation cascade leading to fibrin formation, reinforcing the platelet plug Activation of the fibrinolytic system which digests the haemostatic plug, re-establishing vascular patency

Answer 60

arterial circ - MI/stroke, platelet rich, antiplatelet venous circ - DVT/PE, fibrin rich, anticoags

Answer 61

``` venous Acquired Age, previous VTE Surgery/trauma, immobility, obesity Cancer, serious illness Pregnancy, contraceptive pill, HRT Inherited (Thrombophilia) ``` ``` ARTERIAL Smoking Obesity Hypertension Diabetes mellitus Older age Not inherited thrombophilia ```

Answer 62

Advantages of DOACs Rapid onset of action Fixed oral dosing with predictable anticoagulant effect Low potential for food or alcohol interactions Low potential for drug interactions No need for blood monitoring Disadvantages of DOACs Renal elimination No specific antidotes for the Xa inhibitors Licensed for only specific indications

Answer 63

<8g/dl causes signs of hyperdynamic circulation: - tachycardia - flow murmur - cardiac enlargement - increased cardiac output

Answer 64

1. check reticulocyte count - > increased -> haemolysis? yes = haemolytic anaemia, no = recent bleed - > decreased or normal -> any evidence of renal or endocrine failure or chronic inflam? then = anaemia of renal, endocrine or chronic disease - > if not then consider a primary bone marrow problem (pure red cell aplasia, MDS, MM, infiltration) -> bone marrow ix

Answer 65

iron = duo/jejunum folate = jejunum b12 = ileum

Answer 66

trans = transferrin stored = ferritin, haemosiderin

Answer 67

``` pres Fatigue Pallor Pica Nail changes - koilonychia (spoon nails), brittleness Hair loss Mouth changes - angular stomatitis, atrophic glossitis (burning) Faintness Dyspnoea ``` causes Inadequate intake - poor diet, poverty Poor absorption - poor acid production, gastric surgery, coeliac Excessive loss - GI bleeding (unknown loc), peptic ulcer, diverticulosis, neoplasm, menorrhagia Excessive iron requirement - infancy, preg, hookworm ``` ix Hb and haematocrit <13g/dL (men), <12g/dL (women) MCV <80fL = microcytic MCHC Low = hypochromic Peripheral blood smear - Hypochromic - Microcytic - Anisocytosis (different size) - Poikilocytosis (different shape, pencil) Iron studies (FITT) - Serum iron - low - Serum ferritin - low (<12ng/mL is diagnostic, but dont forget its an acute phase protein so raised in any infection, inflam, malignancy) - Total Iron Binding Capacity - increased - Transferrin saturation - low Investigations for cause - Coeliac serology, H. pylori/urease breath test, UGI/LGI endoscopy (rule out malignancy) ``` ddx chronic disease - 20% sideroblastic mgmt oral iron replacement - ferrous sulphate 2-3mg/kg/day in 4 doses, for 3-6 months SE = constipation, black stools, vomiting diet - dark-leafy green veg, meat, iron-fortified bread consider transfusion - if symptomatic at rest or hb <70 or <80 with cardiac illness, old etc

Answer 68

when to suspect microcytic hypochromic anaemia not responding to iron sideroblast = Atypical abnormally nucleated erythroblast with perinuclear iron accumulation mech Ineffective erythropoeisis. Increased iron absorption but can’t incorporate to haemoglobin causes Congenital - inherited XLSA (x-linked) Acquired - MDS (myelodysplastic syndrome), myeloma, PRV, pyridoxine (B6) deficiency, alc, anti-TB meds ``` ix Hb and haematocrit <13g/dL (men), <12g/dL (women) MCV <80fL = microcytic MCHC - Low = hypochromic Peripheral blood smear - Dimorphic population of normal and hypochromic red blood cells Iron studies (FITT) - Serum iron - high - Serum ferritin - high - TIBC - low Marrow aspirate - Perinuclear ring of iron granules with Prussian Blue ``` ``` mgmt mainly supportive iron chelation = desferrioxamine repeat transfusion - if sympt at rest avoid alc + vit c as these increase iron absorption if hereditary consider pyridoxine (B6) ``` haemosiderosis = iron deposition at liver kidney and heart

Answer 69

normal - 2x alpha 2x beta chains HbF = 2 x alpha 2 x gamma HbA2 = 2xa 2x delta

Answer 70

``` what is it Inherited microcytic anaemia caused by mutation in beta-globin gene. autosomal recessive chromosome 11 β0 - complete absence β+ - some beta-globin ``` epi med, africa, south east asia patho Decreased/absent synthesis of beta-globin leads to excess alpha production + membrane damage/cell destruction Ineffective erythropoeisis cells cant survive - 1. anaemia 2. erythroid hyperplasia - bony changes in skull (flat bones, air space sinus, vertebral bodies) skull bossing + Extramedullary hematopoiesis - hepatosplenomegaly TYPES 1. silent carrier -> normal haem 2. minor/trait -> B/B+ or B/B0, usually asymp, mild anaemia (confused with IDA) 3. intermedia -> β+/β+ or β0/β+, similar pres as maj but as toddler 4. major (aka cooleys anaemia) β0/β0, Complete absence HbA, presents at months with progressive pallor and abdo distension + skull bossing (or chipmunk face) + failure to thrive ix FBC- microcytic anaemia Peripheral blood smear: - Microcytic - Target cells - Nucleated red cells Reticulocyte count- Elevated (haemolytic) **Haemoglobin analysis (electrophoresis)** - Major: No HbA, elevated HbF and HbA2 - Intermedia: Decreased HbA, elevated HbF and HbA2 - Minor/Trait: Mostly HbA, elevated HbF and HbA2 LFT - Elevated total and unconjugated bilirubin (haemolytic) XRay skull - Hair on end sign, widening of diploeic space AUSS - Hepatosplenomegaly mgmt minor - genetic counselling + iron advice inter - genetic counselling + transfusion at symptomatic anaemia (infection, perioperative) + iron monitoring with chelation (desferrioxamine) 3. maj - Genetic counselling + regular transfusion to >10g/dL + iron monitoring with chelation +/- splenectomy +/- assessment for haematopoeitic stem cell transplant comps 1. Thrombotic 2. Complications of iron overload a - Arthropathy (MSK) b - Pigmentation and bronzing c - Arrhythmias and contractile dysfunction -> congestive heart failure d - Endocrine anterior pituitary -> slow growth, delayed sexual maturation pancreatic islet cells -> impaired insulin secretion (T1DM) 3. Transfusion reactions + transmission acquired infections (HIV, HBV, HCV) 4. Splenectomy complications

Answer 71

Splenomegaly results from multiple transfusions, iron deposition and extramedullary erythropoeisis and can lead to hypersplenism. This leads to an increased transfusion requirement and a decreased red cell survival as well as leukopenia and thrombocytopenia.

Answer 72

what is it Inherited microcytic anaemia caused by mutation in alpha-globin genes. autosomal recessive chromosome: 16 Different mutations: α0 (--/) - both alpha genes on same chromosome deleted α+ (α-/) - one of two alpha globin genes is deleted on same chromosome patho 1. Decreased/absent synthesis of alpha-globin leads to excess beta production 2. There are 2 copies/alleles of the alpha globin gene on each chromosome 16 (α1 and α2) 3. Ineffective erythropoeisis - anaemia and haemolysis epi Corresponds to malaria distribution - sub-saharan africa + middle east + south east asia TYPES 1. silent carrier - 1 of 4 alpha globin genes affected - asymptomatic 2. trait - 2 of 4 alpha globin genes affected - heterozygous (α0/α) or (α+/α+) - mild anaemia (hypochromic, microcytic) or normal Hb, confused IDA 3. HbH disease - 3 deletions (α0/α+) - leads to beta tetramers - detected on electrophoresis - anaemia + splenomeg 4. major or bart hydrops fetalis - Homozygous (α0,α0), all 4 alleles affected death in utero pres RF - fh, malaria, geo Symptoms of anaemia - fatigue, dizziness, SOB Splenomegaly Presentation in childhood - more severe, growth retardation Symptoms of gallstones - bloating, abdo pain, gallstones common in HbH ``` ix FBC - Microcytic anaemia (MCV low, MCHC low) Peripheral blood smear: - Microcytic/hypochromia - Target cells - Basophilic stippling in HbH Reticulocyte percentage- Elevated (haemolytic) Haemoglobin analysis (electrophoresis): - Presence of HbH, Hb Bart, will not detect silent carrier or trait Iron studies: - Serum iron - normal or elevated - Serum ferritin - normal or elevated ``` mgmt genetic counselling + iron advice (avoid unless deficient) HbH - + folic acid (1mg, PO) + education + regular transfusion to >10g/dL + iron monitoring with chelation +/- splenectomy +/- assessment for haematopoeitic stem cell transplant crisis - identify cause + monitor + folic acid +/- red cell transfusion

Answer 73

Haemolysis is the premature destruction of RBC. It can happen in two places: 1. Within circulation/Intravascular: a. Trauma e.g. mechanical heart valve b. Complement mediated lysis Reticuloendothelial system/Extravascular: a. Macrophages of liver b. Spleen c. Accelerated red cell destruction due to immune targeting by antibodies

Answer 74

causes 1. Hereditary: a - Enzyme defects - Glucose 6 phosphate dehydrogenase deficiency b - Membrane defects - Hereditary spherocytosis, elliptocytosis c - Abnormal Hb production - Sickle cell anaemia, thalassaemia 2. Acquired: a - Immune mediated b - Non-immune mediated ACCQUIRED Immune mediated: - Caused by autoantibodies and direct antiglobulin +ve (Coombs’ positive) - Often part of other AI cond (SLE/reactive arthritis/scleroderma) - Divide into 2 subtypes depending on temperature at which antibody binds to RBC: 1. Warm IgG mediated - Rx: steroids 2. Cold IgM mediated - Rx: keep warm Non-immune mediated: - Direct antiglobulin -ve - Infection (e.g. malaria), trauma, microangiopathic haemolytic anaemia (DIC, TTP, HUS, HELLP), hypersplenism, liver disease - Paroxysmal nocturnal haemoglobinuria: a - Rare membrane defect b - Haemoglobinuria, marrow failure + thrombophilia, Dx: urinary haemosiderin ``` pres anaemia symps jaundice splenomeg episodic dark urine presence of RF - AI disorders, prosthetic heart valve, family origin Med or middle east, family history haemoglobinopathy or RBC membrane defect, PND, Cephalosporins, fava beans ``` ix FBC + MCHC + reticulocyte count: - Low Hb - Increased MCHC suggestive of spherocytes and reticulocytes - Reticulocyte count >2% Unconjugated bilirubin - Mildly elevated Urinalysis - Haemoglobinuria LDH and Haptoglobin: (this will bind free haemoglobin in intravascular causes) High and Low, n.b. High LDH and low haptoglobin is 90% sensitive for haemolytic anaemia Peripheral blood film: - Sickle cells - Spherocytes - Elliptocytes - Heinz bodies: bite and blister cells - G6PDD - Hypochromic - thalassaemia Coombs test - blood cells washed and incubated with Coombs’ reagent - look for agglutination, Positive for immune mediated Other tests - creatanine/urea (raised in TTP or HUS), LFT (elevated in liver disease), Donald-Landsteiner antibody in cold-immune disease mgmt coombs posi - Treat underlying + support (packed RBC transfusion, if symps + folic acid for RBC prod) combs neg: - valve - cardiology eval - TTP - plasma exchange - Paroxysmal Nocturnal Haemoglobinuria - corticosteroids + anticoag - hypersplenism - splenectomy membrane disorder - splenectomy + support G6PDD - avoid triggers + support haemoglobinopathies - support + disease specific

Answer 75

Increased breakdown? - Increased bilirubin, increased urobilinogen, increased LDH Increased production? - Increased MCV by increased reticulocytes, marrow hyperplasia Extravascular or intravascular? - Intravascular - increased free plasma Hb and decreased haptoglobin, increased haemoglobinuria (no blood cells) - Extravascular - splenomegaly

Answer 76

what is it An inherited X-linked recessive (G6PD gene) enzyme deficiency common among parts where malaria (protective) is common: Mediterranean, sub-Saharan Africa, Asia patho G6PD catalyses step one of pentose phosphate pathway (similar glycolysis) which generates NADPH (important for red cells to protect from oxidative stress) ``` pres prolonged neonatal jaundice or haemolytic anaemia pallor dark urine - suggests intravascular haemolysis nausea vom dehydration AKI - haemoglobin precip ``` triggers: infection broad beans drugs that cause oxidative stress - sulphonamides, cephalosporins ix See haemolytic anaemia investigations Peripheral blood smear: - Blister/bite cells - suggestive of oxidative stress as cause of haemolysis - Heinz bodies - fragments of denatured haemoglobin Genetic testing for G6PD variants mgmt treat as acute haemolysis: - Maintain fluid intake - Folic acid 5mg orally (for RBC production) - Blood transfusion if severe anaemia (<7g/dL) - Renal support if renal impairment by haemoglobinuria (EPO)

Answer 77

characteristic anaemia and evidence of immune system activation due to Inflammation mediated reaction and decreased RBC production + decreased survival ix Normocytic normochromic/microcytic hypochromic hb Low reticulocyte count as of underproduction by marrow (typical in ACD) due to EPO Low serum iron Low TIBC Low transferrin saturation Elevated ferritin patho Release of pro-inflammatory cytokines by infection, neoplasm, autoimmune, trauma (VITAMIN CDEF) Cascade leads to fall in serum iron and decreased RBC survival IL-1 and IL-6: 1. upregulate hepcidin synthesis Hepcidin is a regulator of iron metabolism produced by the liver 2. Down regulates ferroportin (which exports iron from enterocyte) Less free iron for erythropoeisis (and micro-organism growth) and cytokine induced shortening of RBC life causes - VITAMIN CDE Vascular Infective/inflammatory - Chronic: TB, fungal, hepatitis, HIV, Acute: pneumonia, pyelonephritis, endocarditis, cellulitis Traumatic Autoimmune - RA, SLE, dermatomyositis, PMR, scleroderma Metabolic Iatrogenic Neoplastic - lymphoma, carcinoma Congenital Degenerative - CKD, CHF, chronic lung disease Endocrine - DM mgmt treat underlying disease RBC trans if symptomatic

Answer 78

def TRIAD: Pancytopenia (BM failure) with hypocellular bone marrow and no abnormal cells (aka On BM biopsy Hypocellularity with no dysplasia or blasts) pres: 1. neutropenia - infections (<1.5) (lymphocytes are typically spared) 2. normochronic, normocytic anaemia - fatigue, pallor, dyspnoea, faintness (<100) 3. thrombocytopenia - bleeding, bruising (<50) 30 yrs old ``` causes acquired: - Idiopathic (50%) - Drug or toxin exposure -> NSAIDs, penicillamine, gold, chloramphenicol, phenytoin - Post virus (especially hepatitis + parvovirus) inherited: - Fanconi anaemia (AR) - Shwachman-Diamond syndrome (AR) ``` assocs PNH, pregnancy, coeliac, SLE patho autoimmune attack on hematopoietic system DNA damage repair mechanisms ix FBC - At least 2 cytopenias Reticulocyte count - <1% Bone marrow biopsy - Hypocellular marrow with no abnormal cell population mgmt If asymptomatic: - Give neutropenic regimen (MASSC risk assessment if NP< 0.5, Full barrier nursing, Avoid IM injections, Look for infection, Check bloods and cultures, Vitals 4 hourly) If severe: - Matched related allogeneic BM transplant (If BM cellularity < 25% can be curative Worry about Graft vs host disease (GVHD)) + RBC and Pt transfusion + ABX (Antibiotics and antifungals to local guidelines)

Answer 79

when immunocomp = 0.5-1.0 severe = <0.5 causes Aplastic anaemia, immunosuppression, chemotherapy, HIV, BM infiltration, Neoplastic disease, infections…… (think decreased prod and increased destruct) sepsis triad T > 38.5 or 2 readings >38.0 (an hour apart) + NP < 0.5 x 10^9/L + hypotension mgmt Sepsis work up (FBC, BC, CRP, ESR etc) + Sepsis 6 with tazocin (tazobactam [beta lactamase inhib] + piperacillin) +fluid challenge + G-CSF (Given S/C to stimulate NP production)

Answer 80

axial skeleton - vertebrae, sternum, ribs, skull long bones biopsy taken from iliac crest

Answer 81

what is it Disease of RBC caused by AR single gene defect in beta chain of Hb (HbA) (valine replaces glutamine in sixth amino acid) resulting in sickle cell haemoglobin (HbS) patho crescent shaped haemoglobin = disrupted blood flow + break (haemolysis), cause varying degrees anaemia, obstruction of small blood caps = painful crises, organ damage, increased vulnerability to infection HbS will polymerise at periods of hypoxia + acidosis epi very common in sub-saharan africa types 1. sickle cell trait = HbSA - protective falciparum malaria, disability @ hypoxia. Venous occlusion may occur at operation therefore require testing before if black. 2. sickle cell disease = HbSS 3. haemoglobin SC disease = HbSC - sickle gene from one parent and haemoglobin C (lysine for glutamine at 6) from other. Make no HbA. 4. sickle cell beta thal ``` precipitated by CHIDS Cold Hypoxia Infection Dehydration Stress ``` ``` symps parents have it jaundice pallor lethargy tachycardia vaso-occlusion - Dactylitis, visual floaters (retinal arterioles), persistent pain in skeleton, chest and abdomen, chronic renal failure, CNS infarct ``` crisis pres 1. Acute chest syndrome: pneumonia like syndrome (due to sickling in pulmonary vasculature) - chest pain, fever, dyspnoea, tachypnoea, ?collapse 2. painful, ischaemia - bone/ abdo - Bone infarction and avascular necrosis femoral head, mesenteric ischaemia 3. aplastic - temp bone marrow failure - severe anaemia - trig = PARVOVIRUS B19 4. splenic sequestration - life threatening sudden enlargement of the spleen leading to hypovolaemia 5. cerebrovascular 6. priaprism - nocturnal + risk of long-term impotence ix Hb- low Reticulocytes - High (10-20%) Bilirubin - high Peripheral blood film - Sickled cells and Howell-Jolly bodies. Target cells at HbSC Sickle solubility test - Doesn’t distinguish HbSS from HbSA - turbid appearance, normal Hb is clear GOLD - Hb electrophoresis - To diagnose variant Iron studies - Normal Other - LFTs, Renal function, LuFT at diagnosis for baseline SHOULD BE DIAGNOSED AT NEWBORN BLOOD SPOT mgmt Give pneumococcal vaccine 5 yrly and penicillin prophylactically for pneumococcus + genetic counselling + parental education *Sequestration prevents blood from leaving spleen -> acute splenic engorgement trigger avoidance manage daily pain Hydroxyurea (with monthly blood tests) - Increases production of fetal haemoglobin - reduces painful crises Repeat blood transfusion to maintain HbS below 30% and Hb > 10g/dL CRISIS GEN MGMT PRINCIPLES: 1. hydration - IV fluids 2. oxygenation 3. pain relied 4. abx as indicated by local guidelines 5. consider exchange transfusion comps Anaemia Liver complications - jaundice, hepatomegaly and gallstones Iron overload from chronic transfusion Dactylitis Leg ulcers Priapism - requires urgent urological aspiration if >4 hours CV - hyperdynamic precordium, flow murmur, cardiomegaly. Treat for heart failure and HTN

Answer 82

what is it Unusually large, structurally abnormal RBCs Defective DNA synthesis which also leads to leukopenia and thrombocytopenia macrocytic anaemia causes B12/folate deficiency + drugs (hydroxyurea) symps Tend to be asymptomatic as slow onset of decreased Hb due to fall in B12 and folate allowing the body to adjust

Answer 83

what is it A type of macrocytic anaemia with absence of neurological signs what is folate used for DNA synthesis + repair (@pregnancy = NT defects) present in Green vegetables, nuts and liver absorbed in prox jejunum + duodenum caused by 1. poor diet - pov, alc, elderly 2. increased demand - preg, renal disease/dialysis, chronic haemolytic anaemia 3. malabsorption - coeliac, tropical sprue 4. drugs, alc, methotrexate - inhibits synthesis folic acid symps Pallor, fatigue, dyspnoea, faintness, tachycardia, heart murmur headache - hallmark sign of megaloblastic anaemia GI - loss of apetite/ weight loss (from increased energy demand of ineffective erythropoeisis) - hallmark sign of megaloblastic anaemia. Diarrhoea if coeliac. skin/mouth - exfoliative dermatitis, glossitis, painful swallowing (inflamed oral mucosa) ``` ix FBC - low haem, raised MCV + MCH, thrombocytopenia, neutropenia reticulocyte count - low peripheral blood smear - macrocytic RBCs and hypersegmented neutrophils serum folate - low RBC folate - low serum B12 - normal LFT - ?alc liver disease ``` mgmt macrocytosis without anaemia - oral folic acid 1-5mg + treat disorder macrocytosis + pancytopenia - oral folic + treat disorder + packed RBC transfusion folic acid for 4 months +/- B12

Answer 84

aka cobalamin what is it A type of macrocytic anaemia with peripheral neuropathy and neuropsych complaints used for: DNA synth, myelination of nerves and red blood cells (without = megaloblastic anaemia + neuropathy) present in - meat, fish, dairy absorbed in - ileum (combined with intrinsic factor) how - 1. B12 released from food in stomach by peptic acid 2. Parietal cells at gastric fundus produce intrinsic factor (IF) 3. IF binds B12 to form an IF-B12 complex 4. Complex travels to terminal ileum 5. Endocytosis occurs and complex binds to transcobalamin which is released into the blood stream caused by - 1. poor diet - vegan, vege, old age 2. decreased gastric breakdown - hx of gastric surg, atrophic gastritis 3. malabsorption - pernicious anaemia, crohns, coeliac 4. drugs - metformin (decreases absorption), PPI, H2 antagonists pres pallor fatigue dyspnoea faintness mild jaundice haemolysis NEURO - Paresthesias, ataxia + loss vibration (posterior column degeneration), peripheral neuropathy, dementia, psychosis SUBACUTE DEGENERATION SPINAL CORD - upgoing plantars, loss knee jerk, loss ankle jerk GI - chronic GI illness, surgery mouth signs - glossitis, angular chelitis ix FBC - Elevated MCV, low haematocrit, 25% do not have anaemia, if severe = pancytopenia Serum B12 - Low Peripheral blood smear - Megalocytes (RBC precursor) and hypersegmented neutrophils -> megaloblastic anaemia Reticulocyte count - Low (decreased production) IF antibody +ve if cause is pernicious anaemia mgmt Symptomatic + severe i.e. pancytopenia + anaemia + neurological = IM hydroxycobalamin 1mg (daily) + refer to neuro/haem + oral folic acid (1mg PO OD) will correct Hb not neuro + admit and blood transfusion mod + no neuro involve - IM hydroxycobalamin 1mg 3x/week for 2 weeks then once every 3 months Need for lifelong therapy

Answer 85

what is it Autoimmune atrophic gastritis -> Atrophy of gastric mucosa with failure of IF and acid production due to autoantibodies to IF leads to B12 deficiency pernicious = causing harm, especially in a gradual or subtle way ``` assoc with other AI diseases -> Thyroid (25%) Vitiligo T1DM Addisons group A blood Women > men x 1.6 ``` risk of GASTRIC CANCER pres anaemia features: lethargy, pallor, dyspnoea neurological features: peripheral neuropathy: 'pins and needles', numbness. Typically symmetrical legs > arms subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy other features mild jaundice: combined with pallor results in a 'lemon tinge' glossitis → sore tongue specific tests: FBC + vit b12 + folate 1. IF antibody 2. Antiparietal cell antibody: - 90% sensitive (not specific - elevated in atrophic gastritis) 3. Serum gastrin (fasting) 4. Schilling test (NO LONGER DONE) (radiolabeled B12) - Oral radiolabelled B12 with IM unlabelled B12 @1 hour later - Collect urine over 24 hours - Normal result shows 10% of radiolabelled B12 in urine, if = impaired absorption there will be less - If impaired absorption give oral radiolabelled B12 with IF - If urinary radiolabelled B12 is high = pernicious anaemia, if low = malabsorption mgmt B12 replacement as in B12 folic acid supplements

Answer 86

1. bone marrow - myeloid (haematopoietic stem cells - blood forming system) 2. lymphatic - lymphoid (can be B/T cell)

Answer 87

Excess of abnormal white cells in peripheral blood - myeloid or lymphoid

Answer 88

Tumour presentation with local or scattered lumps in lymphatic system

Answer 89

Involve BM, liver and spleen with peripheral blood features

Answer 90

myeloid - AML lymphoid - ALL (T or B cell origin). high grade lymphoma (DLBCL)

Answer 91

myeloid - CML myeloproliferative neoplasm (polycythaemia rubra vera, myelodysplastic syndrome) Lymphoid - CLL, low grade lymphoma (follicular, marginal zone), myeloma

Answer 92

pres tumour - bone pain, fever, lethargy, fatigue, night sweats, weight loss bone marrow failure - anaemia (pallor, SOB, fatigue), thrombocytopenia (petechial rash, bleeding, bruising), neutropenia (freq/recurrent infections) eg candida circ cell related - hyperviscocity (headache, neurology eg cranial nerves), infiltration (tissues, organs), skin/gums @ monoblastic AML, hepatosplenomeg, lymphadenopathy, testicular enlargement

Answer 93

what is it Clonal expansion of myeloid blasts in bone marrow, peripheral blood or extramedullary tissue, unable to differentiate into neutrophils diagnostic feature Bone marrow blasts > 20% or peripheral blood epi most common ADULT leukaemia (>65) - can be comp of chemo assoc Myelodysplastic syndrome, Down’s syndrome, bone marrow failure syndromes (e.g. Fanconi, Diamon-Blackfan, aplastic anaemia), smoking ix FBC - Leukocytosis (increase in WCC) with neutropenia, thrombocytopenia, anaemia Peripheral blood film - Blasts + Auer rods (crystallised granules in myeloid blasts) Coagulation panel- As baseline: PT and PTT may be prolonged with normal fibrinogen and D-dimer U+E, LFT, renal function- For baseline Bone marrow biopsy/aspirate (for definitive diagnosis) + immunophenotyping: - Hypercellularity, blasts > 20%, Auer rods - Flow cytometry immunophenotyping/FISH CXR - Pulmonary infiltrates ddx ALL - clinically indistinguishable, requires BM biopsy + immunophenotyping myelodysplastic syndrome - based on number of blasts (blood film >10%, bone marrow <20%) aplastic anaemia - hypocellular bone marrow mgmt Supportive care: Hydration - electrolyte abnormalities Allopurinol - for acute tumour lysis syndrome (increased urate) Leukoreduction - hydroxycarbamide/leukapheresis Transfusions - RBC + platelets Treat infections (complication) INDUCTION CHEMO: Cytarabine and daunorubicin (interferes with all stages of cell cycle) +/- STEM CELL TRANSPKANT AT FIRST REMISSION - allogenic ``` prog 5 yr survival 25% poor prog factors - > 60 years > 20% blasts after first course of chemo cytogenetics: deletions of chromosome 5 or 7 ```

Answer 94

Electrolyte and metabolic disturbance due to breakdown of large number leukaemic cells (hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia, renal impairment)

Answer 95

associated with t(15;17) fusion of PML and RAR-alpha genes presents younger than other types of AML (average = 25 years old) Auer rods (seen with myeloperoxidase stain) DIC or thrombocytopenia often at presentation good prognosis

Answer 96

what is it Malignancy of lymphoid cells (B or T). Undergoes somatic change and undergoes uncontrolled proliferation. Lymphoid cells replace hematopoietic cells. diagnostic Bone marrow blasts > 20%, blood smear leukaemic lymphoblasts epi Rare in adults. Most common childhood leukaemia (75% < 6), girls > boys assoc Down’s syndrome, ionising radiation, Kleinefelter’s, Fanconi anaemia, smoking chromosome Most common cytogenetic abnormality in adults is Philadelphia chromosome - translocation (9,22). BCR-ABL fusion oncogene = poor prognosis ``` CLASSIFICATIONS 1. FAB (french american british): L1 - small homogenous blasts (children) L2 - large heterogenous blasts (adults) L3 - Burkitt large basophilic B cells with vacuoles ``` 2. Immunological - uses surface markers 3. Cytogenetic - chromosomal analysis, Ph chromosome is a poor prognosis extra pres CNS involvement - CNS infiltration by leukaemoid cells presents as papilloedema, nuchal rigidity and meningismus May also have a focal neurology (CN 3, 4, 6, 7) TESTICULAR SWELLING! ``` TYPES from most to least common: Pre B CD10 phenotype Pre T T B ``` ix FBC - Leukocytosis (increase in WCC) with lymphopenia, thrombocytopenia, anaemia Peripheral blood film - Leukaemic lymphoblasts Coagulation panel (for bleeding/petechiae) U+E, LFT, renal function - For baseline Bone marrow biopsy/aspirate (for definitive diagnosis) + immunophenotyping - Hypercellularity, lymphoblasts > 20-25% + Flow cytometry immunophenotyping/FISH/ PCR for t(9,22) CXR + LP + pleural tap - Mediastinal widening (T), leukaemic lymphoblasts, leukaemic lymphoblasts mgmt Supportive care: - Hydration - electrolyte abnormalities - Allopurinol - for acute tumour lysis syndrome (increased urate) - Prophylactic antimicrobials (aciclovir + fluconazole + ciprofloxacin + co-trimoxazole - pneumocystis pneumonia) - Transfusions - RBC + platelets (if pt<10 x 10^9) - Beware neutropenic sepsis Induction chemotherapy (kill leukaemic cells): - Prednisolone, vincristine, daunorubicin (anthracycline) +- tyrosine kinase inhibitor (imatinib) - Intrathecal methotrexate (for CNS disease) Consolidate remission (weeks) Maintain remission (years) - mercaptopurine (daily), methotrexate (weekly), vincristine + pred (monthly) ``` comps Tumour lysis syndrome Neutropenic sepsis Pancytopenia Chemotherapy side effects ``` prog Complete remission 90% at < 30 worst prog: male, <2 >10, WCC > 20, T or B type, philly, black

Answer 97

what is it Uncontrolled proliferation of myeloid cells in bone marrow ``` pres 1/3 may be asymp typical early: Malaise Fever Wt loss Abdominal discomfort due to splenomegaly (elevated WBC count) Night sweats Arthralgia - increased uric acid from cell turnover ``` diagnosis Presence of Philadelphia chromosome/ BCR-ABL fusion gene patho 1. Philadelphia chromosome t(9,22) produces BCR-ABL fusion oncogene (chromosome 22) 2. Produces p210 BCR-ABL protein (p190 @ ALL) 3. Expresses constitutionally active tyrosine kinase on surface of myeloid cells 4. Unregulated cell division course Chronic phase may transform to accelerated (symptomatic) or blast phase (AML) in 10% epi 15 - 20% of adult leukaemias. Median age 50 ix FBC - Leukocytosis (increase in WCC), anaemia, normal platelets, thrombocytosis (chronic/accel), thrombocytopenia (accel/blast crisis) Peripheral blood film: - Almost all WBCs are mature myeloid cells (NP, basophil, eosinophil) - Blasts > 10% - accelerated + basophils > 20% - Blasts > 20% - blast phase Metabolic profile - Raised potassium, LDH, uric acid due to cell turnover Bone marrow biopsy/aspirate - Granulocytic hyperplasia Cytogenetics (FISH) - Philadelphia chromosome mgmt FIRST LINE- Tyrosine kinase inhibitor (imatinib - muscle cramps/heart failure or dasatinib - pleural effusion) +- allogeneic haematopoeitic stem cell transplant + high-dose induction chemotherapy - Blast crisis (see AML) -> leads to pancytopenia - Presence of philadelphia chromosome is GOOD prognosis - event free survival 95%, able to use tyrosine kinase inhibitor for older people who may not tolerate chemotherapy

Answer 98

what is it A malignant disorder of B lymphocytes that escape cell death (apoptosis) involving bone marrow and peripheral blood. Leukaemic cells may infiltrate lymphatic tissue and haemopoietic organs (liver, spleen, bone marrow) epi most common leukaemia triggers pneumonia, increasing age ix FBC - Lymphocytosis (marked), low Hb, low pt Peripheral blood film: - Smudge and smear cells (damage to lymphocytes in slide prep) - Flow cytometry: CD5, CD19, CD23 positive CT scan - Hepatosplenomegaly, retroperitoneal, mediastinal lymph node ddx leukaemic phase of lymphoma criteria/staging BINET: A - < 3 lymphadenopathy + normal Hb and Pt, B - >=3 lymphadenopathy + normal Hb and Pt C - anaemia or thrombocytopenia with any lymphadenopathy mgmt A + B + asymptomatic - watch and wait. Monitor with FBC, flow cytometry every 3 months C - chemotherapy: rituximab + cyclophosphamide + fludarabide +- stem cell transplant comps 1. Hypogammaglobulinaemia - lymphocytes are dysfunctional and can’t produce antibodies. Pt deficient in IgG, IgA, IgM therefore increased infection risk (can give monthly IVIG) 2. Autoimmune haemolytic anaemia - dysfunctional antibodies directed towards RBCs. Give prednisolone 3. transformation to high grade lymphoma - richters transformation (become very unwell very suddenly)

Answer 99

non-hodgkin's lymphoma

Answer 100

what is it basically all the ones that aren't hodgkins Lymphomas are solid, leukaemias are circulating most common Most common is diffuse large B-cell lymphoma (mainly from B cell lines) -May produce immunoglobulins. T cells can travel to extranodal sites e.g. skin and CNS epi 5x more common than hodgkins older, caucasians, hx of chemo/radio, fh, recent viral infection, AI, immunodeficient subtypes 1. Diffuse large B-cell lymphoma (30%) - aggressive/high grade 2. Follicular lymphoma (20%) - indolent/low grade 3. Burkitt’s (HG) (1%) - EBV - characteristic jaw lymphadenopathy (child) 4. Primary CNS lymphoma (1%) - EBV with AIDS 5. MALT (LG) (gastric mucosa associated lymphoid tissue) - H.pylori 6. Marginal zone - massive splenomegaly 7. T cell assoc AI disorders - sjogren's, RA, SLE, coeliac immunodeficiency pres nodal - painless lymphadenopathy, asymmetrical (can be rapid) extranodal (MUCH more common than in hodgkins): 1. Bone marrow - pancytopenia (fatigue, dyspnoea), bone pain 2. Splenomegaly (massive in marginal zone) + hepatomegaly 3. Dry cough - mediastinal mass/pneumonia 4. Skin (T cell) 5. Gut: diarrhoea, vomiting, abdo pain (MALT) 6. Bone pain 7. CNS - nerve palsies B symptoms ( less so than in hodgkins) ix FBC + blood film - Thrombocytopenia (liver or BM), or pancytopenia (BM) Lymph node core biopsy/skin biopsy/bone marrow biopsy (for flow cytometry - tumour surface markers and cytogenetics) +ve LDH: Elevated - proliferative rate of lymphoma ESR CT scan/MRI - For staging Other - LP, LFT (mets), HIV test ddx 1. Hodgkin’s lymphoma (bimodal 20s and 60s, pruritus and alcohol pain) - Reed Steenberg cells 2. ALL (acute onset, purpura, bleeding, infection) - blast cells 3. Infectious mononucleosis - with pharyngitis and rash ``` staging ANN ARBOR 1 - Single lymph node group 2- Multiple on same side diaphragm 3 - Multiple on opposite side diaphragm 4 - Multiple extranodal sites or lymph nodes and extranodal disease E - extranodal extension B - weight loss > 10%, fever, drenching night sweats A - no B symptoms (B symps = worst prog ``` mgmt for diffuse large b cell lymphoma or stage 3-4 follicular lymphoma R-CHOP-21 (6-8 cycles) +/- CNA proph - intrathecal methotrexate +/- growth factor - G-CSF - filgastim +/- antimicrobial proph - cipro + acic + fluconazole prog DLBCL - S1/2 - 80% cure rate, S3/4 - 40% cure rate FL - incurable comps Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia Superior vena cava obstruction Metastasis Spinal cord compression Complications related to treatment e.g. Side effects of chemotherapy

Answer 101

It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of norma

Answer 102

what is it malignant proliferation of lymphocytes arises from mature B cells pres cervical or supraclavicular lymphadenopathy (painless) Risk factors B symptoms (25%) - pel ebstein fever Pruritus (10%) Alcohol induced pain Symptoms of mediastinal adenopathy - Dry cough, Dyspnoea, Chest pain, Superior vena cava syndrome (facial and upper limb oedema, dilated vessels) diagnostic Presence of Reed-Sternberg cells (large, multinucleated, mirror image nuclei, may contain EBV) epi bimodal @ 25 + 50 most common type nodular sclerosing - 70% others - mixed cellularity lymphocyte rich/ depleted causes Primary immunodeficiency - ataxia-telangiectasia, Wiscott-Aldrich Secondary immunodeficiency - HIV/transplants Infection - EBV Autoimmune disorders - SLE patho Impaired immunosurveillance of EBV infected cells. B cells escape regulation and proliferate RF EBV Positive hamily history Young adult from higher socioeconomic class staging - ann arbor ``` ix FBC - low hb, pt, WCC high or low ESR - raised is poor prog excisional lymph node biopsy CXR - mediastinal mass PET-CT - staging PCR - EBV baseline liver/renal function ``` mgmt Chemotherapy (ABVD) + Radiotherapy (mainly for the chest) (80% curative) Doxorubicin Bleomycin Vincristine Dacarbizine Be aware of the side effects of chemotherapy and radiotherapy

Answer 103

what is it Plasma dyscrasia: Clonal proliferation of plasma cells in the bone marrow associated with monoclonal element (Ig or Ig fragment) in serum or urine It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells pres chronic relapse/remit Bone pain (esp back pain!) - osteolytic lesions + fractures, vertebral collapse (high osteoclast activity) Anaemia Fatigue recurrent bact Infections Hypercalcaemia - bone break down babes Renal impairment - due to light chain deposition and precipitation of light chains with Tamm-Horsfall protein in ascending loop of Henle Bleeding -bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising diagnosis serum and urine protein electrophoresis 3 main assocs 1. Osteolytic bone disease + hypercalcaemia 2. Anaemia - by accumulation plasma cells in BM 3. Renal disease epi Most common haematological malignancy Mean age is 60/70 classification spectrum: m-protein is monoclonal component 1. MGUS - monoclonal gammopathy of unknown significance (may progress): M-protein < 30g/L, bone marrow clonal cells <10% 2. SMOULDERING myeloma - asymp: M-protein > 30g/L OR bone marrow clonal cells >10%, No related organ or tissue involvement (including bone lesions) 3. ACTIVE myeloma - symps - A - M-protein > 30g/L OR bone marrow clonal cells >30% (10% = minor, 30% = major) 1 major + 1 minor B - CRAB (tissue/organ involvement): Calcium elevation (>2.75mmol/L) Renal insufficiency (Cr > 173mmol/L) Anaemia (Hb < 10g/dL or 2g/dL below normal) Bone disease - lytic or osteopenic ix REMEMBER EVIDENCE OF END ORGAN DAMAGE 1. serum electrophoresis - GOLD (Paraprotein spike IgG > 30g/L, IgA > 20g/L, light chain urinary excretion >1g/day Bence Jones, hypogammaglobulinaemia) 2. skeletal survey, whole body MRI - Osteopenia, osteolytic lesions (e.g. pepper pot/raindrop skull), pathological fractures 3. BM aspirate + trephine biopsy - Plasma cell infiltrate >10% (minor) or >30% major 4. blood film - rouleaux formation 5. serum ca -> raised 6. FBC - anaemia 7. creatinine/urea - raised 8. ESR - raised with increased viscosity mgmt must begin immediately TREAT COMPS Bone disease: Hypercalcaemia + pain - bisphosphonates + analgesics Anaemia - blood transfusion/EPO Spinal cord compression - dexamethasone Hyperviscosity (reduced cognition/blurred vision) - plasmapheresis AKI - rehydration/ preserve good hydration Infection - antibiotics + pneumonia/flu vaccine, IVIG VTE proph MGUS - Monitor closely with urine/serum electrophoresis 6 monthly considering transplant (younger/healthier): (bortezomib) based induction + dexamethasone + DVT prophylaxis (aspirin 75mg OD) + autologous/allogeneic stem cell transplant no transplant: Thalidomide + an Alkylating agent + Dexamethasone completion of treatment - monitor every 3 months- bloods, electropheresis relapse - bortezombin monotherapy

Answer 104

Rapid growth of myeloma cells (in BM) inhibits formation of osteoprogenitor cells and osteoblasts Production of macrophage inflammatory protein 1 alpha (MIP1a) stimulates osteoclastogenesis and Dkk-1 inhbits osteoblasts Imbalance leads to hypercalceamia and hypercalciuria

Answer 105

serum electrophoresis and ESR

Answer 106

Criteria: req 1 major and 1 minor Major Plasmacytoma on BM biopsy BM plasmacytosis > 30% Monoclonal spike as 1a. Minor Plasmacytosis 10-30% Smaller monoclonal spike Lytic lesions

Answer 107

polycythaemia vera

Answer 108

what is it Polycythaemia is increased proportion of haemoglobin in the blood either by: Relative - decreased plasma volume: 1. Acute - dehydration, alcohol, diuretics 2. Chronic - smoking, obesity Absolute - increased red cell numbers: 1. Primary - polycythaemia rubra vera 2. Secondary - high altitude, chronic lung disease (hypoxia), or increased EPO due to renal carcinoma Polycythaemia rubra vera = is a myeloproliferative (overactive BM) disorder of predominantly red cells (but also WBC and Pt) DEFINITION: Clonal hematopoietic disorder with erythrocytosis, thrombocytosis, leukocytosis and splenomegaly aetiology 95% JAK2 V617F somatic mutation n.b. Ph chromosome -ve (differentiates from CML) symps hyperviscosity = Headache, tinnitus, dizziness, visual disturbance, plethoric appearance (red and full) thrombosis/bleeding = Stroke, MI, PE, thrombophlebitis, DVT, haemorrhage bath = Pruritus after hot bath, erythromelalgia (pain) + redness of fingers, palms, heels toes ix FBC/film - Raised haemoglobin, raised haematocrit, raised WBC, raised Pt LFT for Budd-Chiari syndrome (raised) JAK2 gene mutation screen (e.g. PCR) serum ferritin U+E low ESR BM biopsy- Hypercellular with trilineage growth Chromium studies - Elevated RBC mass EPO- Low with high Hb -> PV MCV - Low MCV with normal Hb -> PV with IDA diagnosis >0.52 men >0.48 women haematocrit OR raised red cell mass >25% above predicted mutation in JAK2 mgmt aim - to keep low haematocrit + reduce risk of thrombosis 1. Phlebotomy/venesection (for low risk, ie. <60 and no thrombosis) 2. Cytoreduction (for high risk) - hydroxycarbamide 3. Low dose aspirin (75mg) 4. Management of CV risk factors (DM, hyperlipidaemia, HTN, smoking) comp 10-15% transform to AML

Answer 109

PV has no philadelphia chromosome | Neutrophil alkaline phosphatase is raised in PV but decreased in CML

Answer 110

what is it group of malignant haematopoietic disorders characteristics 1. dysplastic changes in one or more cell lineages 2. ineffective hematopoiesis 3. predilection to develop AML ``` patho bone marrow becomes hyper/hypocellular peripheral blood cytopenias affects different cell lines: - myeloid WBC - erythroid RBC - megakaryocyte platelet ``` aetiology primary - 90% secondayr - worst prog - due to radio/cancer epi >70 male smoker pres 1. anaemia -> Unexplained macrocytic anaemia: fatigue, exertional dyspnoea, worsening of angina, CCF 2. neutropenia -> If granulocyte depletion - recurrent infections/sepsis 3. thrombocytopenia -> Decreased platelets: BLEEDING, petechia, bruising, nosebleeds, bleeding gums, ecchymosis (discolouration from bleeding) ``` ddx macrocytic anaemia -> B12/folate def neutropenia -> viral infection, drugs thrombocytopenia -> ITP, drugs all of above -> CML, BM failure, aplastic anaemia ``` diagnosis of EXCLUSION + dysplastic cell morphology -> FBC + blood film: Anaemia (normo/macrocytic) Neutropenia, thrombocytopenia, neutrophilia, thrombocytosis Dimorphic red cells, Pappenheimer bodies, anisocytosis, poikilocytosis -> ferritin + B12 - normal -> renal func, LFT, CXR, ECG - co-morbs BM asp/biopsy + cytogenetics - hypercellular with blasts mgmt Supportive blood and platelet transfusions + monitoring iron status (ferritin) EPO + granulocyte colony-stimulating factor (G-CSF) If sepsis - broad spectrum ABX If recurrent infections - G-CSF High-intensity chemotherapy comps anaemia, thrombocytpenia, neutro transfusion related iron overload -Chronic fatigue, Joint pain, Abdominal pain, Liver disease (cirrhosis), Irregular heart rhythm/heart failure, Bronze/ashen grey skin --> desferrioxamine transform to AML bone marrow failure - leading cause of death median survival - 2 yrs

Answer 111

what is it Mainly AR inherited bone marrow failure syndrome Cells derived are sensitive to DNA cross-linking pres 1. Congenital dysmorphic features; - Triangular faces - Cafe au lait + hyperpigmented skin - Cardiac and renal malformations - Abnormal thumbs - Short 2. Pancytopenic bone marrow failure 3. Susceptibility to cancer (AML, solid tumours - head and neck squamous cell carcinoma, gynaecological cancers <50)

Answer 112

decreased production: 1. BM infiltration - leukaemia, lymphoma, myeloma, myleofibrosis 2. liver disease - reduction of TPO 3. decreased BM production - low B12/folate, aplastic anaemia, infection 4. dysfunctional prod - myelodysplasia increased destruction 1. autoimmune - ITP 2. hypersplenism 3. drug related - heparin 4. consumption of platelets - DIC, TTP, HUS, haemorrhage

Answer 113

``` what is it isolated thrombocytopenia (<100) thought to be due to autoimmune phenomenon and antiplatelet autoantibodies leading to rapid clearance in spleen ``` typically occurs in: children with a preceding viral illness or middle aged women pres bleeding - petechiae on skin or mucosal membrane, haemorrhagic bullae in oral cavity/tongue, gum/mucocutaneous bleeding, menorrhagia ddx must ddx from delayed visceral bleed of coag disorders 1. Pseudothrombocytopenia 2. Thrombocytopenia due to liver disease or alcohol - raised GGT, alk phos 3. TTP - may have neurological changes or fever + anaemia 4. DIC - prolonged PT and aPTT 5. Drug induced 6. Splenomegaly ix FBC - pt count <100 peripheral smear - rules out pseudothrombocytopenia due to clumping/poor counting bone marrow biopsy - increased megakaryocytes, no evidence of malignancy causes of secondary ITP - HIV serology, H.pylori, hep B/C serology, SLE, drug induced (eg quinine) mgmt severe active bleeding - immunosuppression: IVIG + pred + pt transfusion (works in 1-5 days for 4 weeks) chronic? give rituximab (anti-b cell ie antibody) + splenectomy if <2 consider wiskott-aldrich IN CHILDREN - usually self-limiting -2 weeks

Answer 114

what is it MEDICAL EMERGENCY - 95% fatality clinical syndrome with microangiopathic haemolytic anaemia and thrombocytic purpura ``` pres PENTAD: 1. fever 2. renal failure - raised urea + creat 3. haemolytic anaemia - pallor jaundice 4. thrombocytopenia -> purpura, ecchymosis, menorrhagia 5. neurological change - coma, focal neurology, seizure, headache, confusion + GI - N+V/d ``` patho 1. Absence of VWF cleaving protein (ADAMTS-13) 2. Leads to large VW multimers 3. Spontaneous platelet aggregation in microvasculature (brain, kidney, heart) 4. Red cells passing clots subjected to shear force and rupture -> haemolytic anaemia ``` RF black fat female preg ``` ``` causes post infection pref drugs - ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir SLE HIV ``` ``` ix FBC - decreased pt, hb <80 reticulocyte count - high LDH + bilirubin - raised peripheral blood smear - microangiopathic blood film with schistocytes - RBC fragments U+E - raised urinalysis - proteinuria ``` mgmt urgent plasma exchange + pred (immunosup) + antiplatelet agent (aspirin) long-term aspirin to decrease platelet aggregation DO NOT GIVE PLATELETS rituximab - easy method for targeting antibody production

Answer 115

suspect if CRITICALLY ILL 1. Severe sepsis or obstetric or malignancy 2. Shock 3. Extensive tissue damage - trauma and burns pres shock - oliguria, hypotensive, tachy bleeding - brusing, purpura, haemorrhage, petechiae, oozing, haematuria GEN BLEEDING from 3 unrelated sites = DIC how coag pathways activated diffuse fibrin deposition at microvascular circ consumption of coag factors and platelets dereased: 1. platelet count 2. fibrinogen 3. factor v/8 ``` increased: PT (extrinsic pathway) aPTT (intrinsic pathway - activated partial thromboplastin time) D-dimer fibrin degradation products ``` ``` mgmt treat cause eg sepsis to intensive care supportive care -stop bleeding: - FFP - replace coagulation factors - cryoprecipitates - second line but dont require ABO match - platelet transfusion <20 ```

Answer 116

toddlers x-linked recessive so only little boys bleed into muscles and joints

Answer 117

teenagers AD on chromosome 12 bleed into mucus membranes and skin

Answer 118

inheritance x-linked recessive - skip a gen types A = F8 deficient B = F9 deficient (christmas disease) F8 < 1% = severe - spontaneous bleeding to muscles/joints crippling arthritis 1-5% = mod - bleed post minor trauma >5% = minor - bleed post surgery mgmt Treat with recombinant F8 or F9 concentrate (IV at bleed) + avoid IM injections, aspirin and NSAIDS if mild haemophilia A - give desmopressin IV DDAVP -> stimulates endogenous release F8 + VWF

Answer 119

AD chromosome 12 - defective production of VWF = defective platelet plug formation and F8 deficiency Clinically: bruising, prolonged bleeding, mucosal bleeds, epistaxis, menorrhagia Management is severity dependent Type 1 = DDAVP Severe give additional recombinant F8

Answer 120

aka HHT - hereditary haemorrhagic telangiectasia characteristics vascular dysplasia -> telangiectasia inheritance AD ``` diagnosis 3 of: - epistaxis (recurrent) - telangiectasia - visceral lesions - family hist ``` pres sharply demarcated mucocutaneous lesions mgmt treat severe haemorrhage with blood transfusions

Answer 121

synthesis of 1972 fat soluable vitamin deficient in malabsorption especially obstructive jaundice mgmt - IV vit K

Answer 122

Series of proteolytic enzymes that circulate in inactive state which are sequentially activated Generate thrombin that cleaves fibrinogen creating fibrin = clot

Answer 123

Endothelium damaged Platelets adhere via collagen and VWF and GP1b Binding of collagen stimulates cytoskeleton shape change Activation causes degranulation Alpha - PDGF, TGF-beta Delta - ADP + ATP (amplification) + Ca2+ Aggregation: cross linking of platelets by fibrin Activated platelet allows binding of coag factors

Answer 124

platelet function

Answer 125

coagulation cascade

Answer 126

aspirin Irreversibly inhibits COX1 and prevents production of thromboxane A2. TXA2 induces platelet aggregation and vasoconstriction (75-300mg od) for arterial thrombosis clopidogrel Irreversible P2Y12 antagonist. P2Y12 is activated by ADP and amplifies platelet activation by activating glycoprotein Gp2b3a. Inhibits ADP induced platelet aggregation.

Answer 127

works on intrinsic pathway - aPTT- measures all factors except F13 (fibrin) + F7 (tissue factor) Heparin is a glycoaminoglycan Binds to antithrombin and increases activity, inactivates thrombin and FXa comp - heparin induced thrombocytopenia LMWH - dalt is smaller and therefore renally excreted, mech inactivates FXa

Answer 128

extrinsic pathway WEPT 1972 uses PT - measures F7 + 1,2,5,10 Prevents synthesis of FII, VII, IX, X It is a vitamin K antagonist with a long half life It prolongs the PT It is monitored with INR (international normalised ratio derived from prothrombin time) Aim 2-3

Answer 129

FXa inhibitors - apixaban, rivaroxiban Thrombin inhibitors (FIIa) - dabigatran Indicated for DVT/PE and AF require no monitoring The problem is they are NOT easily reversible

Answer 130

Thrombosis is blood coagulation within a vessel May occur in arterial circulation - high pressure, platelet rich (atherosclerosis + RF) Venous circulation: low pressure, fibrin rich (DVT + PE)

Answer 131

``` Antiphospholipid syndrome Cancer Slow flow - sickle cell, PRV Nephrotic syndrome Obesity Pregnancy ```

Answer 132

1. INFECTION HBV HCV HIV 2. ACUTE - non infectious Acute haemolytic reaction - ABO incompat Febrile, non-haemolytic reaction - hypersensitivity to allergens in plasma (IgE) Allergic/anaphylactic reaction - Result of granulocyte activation in pulmonary vasculature - increased permeability Transfusion-associated circulatory overload Transfusion-related acute lung injury (TRALI) DELAYED non infectious Iron overload Delayed haemolytic reaction - Non-preventable - non-ABO aB/antigen incompatability Transfusion-associated graft vs host disease - In immunodeficient patients, transfused white cells react recipient antigens Post-transfusion purpura - Immune thrombocytopenia occurring post transplant of Pt containing component. Recipient prior sensitised to foreign platelet antigen. (preg)

Answer 133

acute haemo discontinue blood + fluid resus

Answer 134

alllergic transfusion discontinue blood + adrenaline + secure airway (intubate) + salbutamol ± antihistamine

Answer 135

febrile non haemolytic stop blood + para

Answer 136

TRALI O2 +/- ventilation IV furose

Answer 137

Delayed haemolytic transfusion reactions supportive

Answer 138

fever | supportive

Answer 139

LUQ mass, moves with respiration, enlarges towards RIF, cannot feel above, dull to percuss.

Answer 140

CHINA - MMM Congestion - p HTN, portal vein thrombosis, budd-chiari, HF Haematological - anamia, thalassaemia, sickle cell, leukaemia Infection - malaria, EBV, CMV, HIV, TB, glandular fever Neoplasm - CML, myelofibrosis, lymphoma Autoimmune/connective tissue - RA, sarcoidosis, amyloidosis, SLE, Chronic Myeloid Leukaemia Myelofibrosis Malaria

Answer 141

``` types 1. Planned 2. Traumatic 3. Autosplenectomy/hyposplenism (physiological loss of function) e.g. sickle cell (splenic infarct) or coeliac -> this leads to an increased risk of infection from encapsulated bacteria (Will see Howell-Jolly bodies (basophilic) in RBC - healthy spleen would normally filter these out Might see Pappenheimer bodies (iron) ) ``` indications 1. Spontaneous rupture at massive splenomegaly (infectious mononucleosis) precipitated by trauma 2. Hypersplenism: ITP, hereditary spherocytosis 3. Neoplasia: lymphoma or leukaemic infiltration 4. Splenic cyst or abscess comps Thrombocytosis - platelet count peaks at 7-10 days (? prophylactic aspirin) *Overwhelming infection: Encapsulated bacteria - s.pneumoniae, h. Influenza, n.meningitidis 4% if no prophylaxis Mortality of 50% for first 2 years mgmt Prophylactic ABX + vaccines Oral phenoxymethylpenicillin + or macrolides (azithromycin/clarithromycin) Pneumococcal vaccine and influenza vaccine Carry health alert card

Answer 142

Before transplant give chemo/radiotherapy Ablative or reduced intensity Harvest BM removed from pelvis under GA Peripheral blood stem cells: from blood via apheresis Give BM IV as inpatient Engraftment

Answer 143

Stem cells harvested from own BM Pt undergoes ablative or reduced treatment (+) rapid immunity, less chance infx, reduced risk rejection (-) not suitable for AML (high relapse)

Answer 144

Healthy donor and patient Must match HLA to patient HLA at 3 Loci Donor normally sibling or relative or identified match

Answer 145

Infection - decreased leukocytes and immunosuppression post procedure Veno-occlusive disease - chemotherapy damages hepatic venous epithelium Mucositis - mouth and throat GvHD - @allogeneic, graft recognises host as non-self and begins immune response against recipients tissues. Typically @<3 months. Skin, intestine and liver commonly affected (maculopapular rash, nausea/vom, cholestatic jaundice) Gv tumour effect - beneficial. Response of donor T lymphocytes against diseased lymphocytes of recipient lead to reduced likelihood of cancer return

Answer 146

in myeloproliferative disorders

Answer 147

PT on extrinsic factors APTT on intrinsic factors 1972 WEPT - warfarin acts on extrinsic pathway and is measured by PT.

Answer 148

Immunoglobulin A (IgA), which is found in high concentrations in the mucous membranes, particularly those lining the respiratory passages and gastrointestinal tract, as well as in saliva and tears. Immunoglobulin G (IgG), the most abundant type of antibody, is found in all body fluids and protects against bacterial and viral infections. Immunoglobulin M (IgM), which is found mainly in the blood and lymph fluid, is the first antibody to be made by the body to fight a new infection. Immunoglobulin E (IgE), which is associated mainly with allergic reactions (when the immune system overreacts to environmental antigens such as pollen or pet dander). It is found in the lungs, skin, and mucous membranes. Immunoglobulin D (IgD), which exists in small amounts in the blood, is the least understood antibody.