Haematology Flashcards

Question

What is the class, action and indication of Clopidogrel?

Answer 1

Class: anti-platelet drug Action: - Irreversibly blocks the ADP-receptor on platelet cell membrane - Therefore inhibits formation of GPIIb/IIIa complex, required for platelet aggregation - Decreased thrombus formation Indication: Secondary prevention of thrombotic events

Answer 2

- JAK2 mutation - These mutations result in continuous activation of JAK receptor regardless of ligand binding - JAK2 is normally activated to stimulate RBC production

Answer 3

Over-production: - Myeloproliferative disorders (myeloid SC) - Lymphoproliferative disorders (lymphoid SC) Abnormal production: - Myelodysplastic syndromes Under-production: - Aplastic anaemia

Answer 4

Hodgkin's disease - Nodular sclerosing - Mixed cellularity - Lymphocyte rich Non Hodgkin's lymphoma - Diffuse large B-cell lymphoma - Follicular cell lymphoma - MALT lymphoma - Lymphoblastic lymphoma - Mantle cell lymphoma Chronic lymphocytic leukaemia

Answer 5

Definition: Production of immature cells from myeloid series from the bone marrow - A type of cancer - Characterised by dysplasia and ineffective haematopoesis in one or more of the myeloid series - Characterised by bone marrow failure (when there is insufficient production of normal RBC, granulocytes/monocytes or platelets) - Some progress to AML Aetiology: secondary to chemotherapy or radiotherapy, or de novo (new)

Answer 6

- MDS with single lineage dysplasia (aka refractory anaemia): under-production of normal erythrocytes - MDS with multilineage dysplasia (aka cytopenic anaemia): under-production of normal erythrocytes, WBCs or platelets - MDS with excess blasts (aka refractory anaemia with excess blasts): under-production of normal RBCs, WBCs or platelets and have a higher risk of developing AML - Sideroblastic anaemia (refractory anaemia with ringed sideroblasts)

Answer 7

- Stem cells (blasts) don't mature properly and accumulate in the bone marrow, pushing out normal cells, and have shortened life-span - Increase in the number of immature cells (blasts) - Increase in abnormally developed cells (dysplastic cells) - Fewer **mature** blood cells in the circulation - Means there are fewer RBCs, WBCs and/or platelets - Bone marrow failure - This can develop indolently (slowly) or agressively (quickly) - Can develop into acute myeloid leukaemia (AML)

Answer 8

Low blood cell counts (Pancytopenia) - Anaemia (low erythrocyte count) - Neutropenia (low white cell count) - Thrombocytopenia (low platelet count)

Answer 9

- Anaemia: Weakness, easily fatigued, SOB, pallor - Neutropenia: increased risk of infection e.g. UTI, skin infection. lung infection - Thrombocytopenia: bruising and easy bleeding (e.g. nosebleeds)

Answer 10

- A benign type of myelodysplasia - The body has enough iron but is unable to use it to make haemoglobin (therefore less haemaglobin in RBCs) - Therefore it accumulates in the mitochondria of erythroblasts, giving a ringed appearance - These cells are called ringed sideroblasts and are found in the bone marrow - Erythroblasts - precursor to erythrocytes, are nucleated and found in bone marrow Characterised by: - Refractory anaemia (underproduction of RBCs) - Hypochromic cells in circulating blood - Ring sideroblasts in the bone marrow

Answer 11

- Usually elderly - 20%: incidental finding of FBC - 20%: present with infection or bleeding - Most present with fatigue due to anaemia Investigations: - Complete blood count - Blood smear (% and morphology of cells) - Bone marrow aspirate and biopsy (% of each cell in the BM)

Answer 12

Supportive care: Blood and platelet transfusions - Growth factors (erythropoietin and G-CSF (granulocyte colony stimulating factor)) to prevent infection and improve QoL High-blast counts: low-dose chemotherapy High-risk of developing AML: intensive chemotherapy Allogenic stem-cell transplant: for selected patients who are well enough to tolerate the procedure i.e. younger (50-70) and no other medical problems

Answer 13

Red pulp - Removal of old, damaged and dead RBCs through phagocytosis by macrophages - Phagocytosis of opsonised bacteria - Sequesteration of platelets (storage of platelets) - Storage of RBCs White pulp - Contains T- and B- lymphocytes and macrophages - Important in the normal immune response

Answer 14

- Extramedullary haematopoiesis i.e. haematopoiesis occuring outside the bone marrow

Answer 15

= Anaemia due to bone marrow failure - Defined as pancytopenia with hypocellularity (aplasia) of the bone marrow - Usually an aquired disease - It's due to a reduction in the number of pluripotent stem cells together with a fault in those remaining meaning they cannot repopulate the bone marrow - This causes deficiencies in blood cells (one or more lineages)

Answer 16

Primary - Congenital e.g. Fanconi's anaemia (10-20% cases) - Idiopathic aquired (50% cases) Secondary - Drugs e.g. chemotherapy - Infections e.g. hepatitis, HIV - Pregnancy

Answer 17

- Increased % of bone marrow occupied by fat spaces Normally - At 30yrs, 30% of the bone narrow should be fat spaces - At 70yrs, 70% should be fat spaces etc. In aplastic anaemia, can see around 90% taken up by fat spaces

Answer 18

Autosomal recessibe inheritance

Answer 19

- Bone marrow failure (can be present from birth into adulthood) - Malignancy - Short telomeres (causing increased cell turnover) Gold-standard for treatment: allogenic stem-cell transplant - Donors need screened for Fanconi anaemia as it's autosomal recesive

Answer 20

- Autologous: use patients own stem cells - Allogenic: use stem cells from a donor Types of donor in an allogenic transplant: - Syngenic: transplant between identical twins - Allogenic sibling: HLA identical - Volunteer unrelated (VUD) - Umbilical cord blood

Answer 21

- Relapsed leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma - Patient given G-CSF +/- chemotherapy to force the stem cells to leave the bone marrow to be collected from the blood - Use mobilised peripheral blood stem cells

Answer 22

- Acute and chronic leukaemia, relapsed lymphoma, aplastic anaemia, hereditary disorders - Use peripheral blood stem cells, bone marrow or umbilical cord blood - In malignancy: benefit of graft-v-leukaemia effect but at the expense of graft-v-host disease

Answer 23

- An immune condition that can occur in those who receive allogenic stem cell transplants - The donor's immune system (immune cells) recognises the host's tissues as foreign and starts to attack it - Manifestation: Skin rash, jaundice or diarrhoea Two forms - Acute: occurs within first 100 days Chronic: occurs after the first 100 days Treated with immunosuppressive agents

Answer 24

- Hidden within GvHD - The immune cells from the donor (same cells causing GvHD) attack the remaining leukaemic cells - Very effective, especially in those who've had difficulty maintaining remission - Also works for lymphoma and myeloma - Minimising GvHD reduces GvL therefore higher risk of relapse - Challange: minimise GvHD and maximise GvL

Answer 25

- GvHD - Limited donor availability - Immunosuppression - Relapse

Answer 26

Drive: erythropoietin (kidneys) Code: Globin genes Substances: folate, B12, minerals, hormones (testosterone, thyroxine) Location: functional bone marrow

Answer 27

Shape: Biconcave - Inc. SA for O₂ transfer - Smaller to fit through small vessels Role: Gas transfer - Transport oxygen from lungs to tissues - Remove CO₂ as a waste product

Answer 28

- 1 Haemoglobin molecule has 4 haem groups and 4 globin chains (2a and 2b chains) - Each haem can bind to one oxygen - Therefore each Hb molecule can bind to 4 oxygen molecules - Hb can bind reversibily to O₂ without being oxidised or reduced

Answer 29

Total body iron: 4g Bone marrow and RBCs: 3g RES (Macrophage store): 200-500mg Myoglobin: 200-300mg Enzymes containing iron): 100mg

Answer 30

Transferrin (Tf) - Glycoprotein - Two iron binding domains on one Tf molecule - 30% saturated with iron - Synthesised in hepatocytes in relation to iron levels - High iron stores: Tf levels drop - Low iron stores: hepatocytes produce more Tf

Answer 31

- Transports iron in plasma to cells with Tf-receptors on their surface i.e. all tissues e.g. erythroblasts (in BM), hepatocytes, muscles etc. - Most Tf-receptors are found on erythroblasts - Each transferrin molecule has two iron binding sites

Answer 32

- Iron is bound to Tf and transported to tissues with Tf-receptors e.g. erythroblasts - Iron is then released into the erythroblast - Most is taken into the mitochondria to make haem - The rest is stored as erythroblast ferritin - Most Tf-receptors are found on erythroblasts

Answer 33

- RBCs remain in circulation for 120 days then are degraded by macrophages in the reticuloendothelial system (RES) Haemoglobin → Haem and Globin - Globin broken down into amino acids - Haem → Iron and bilirubin - Iron can be stored in macrophages as ferratin or haemosiderin - Usually stored as ferritin but if there's a lot of ferritin, iron is stored as haemosiderin (insoluble ferritin aggregates) - From here it can be transported to BM to produce more RBCs - Macrophages found in CT, lymphoid organs, BM, bone, liver, lung

Answer 34

Serum ferritin - A small amount of ferritin is found in serum - Levels of serum ferritin are proportional to RES iron stores - However, serum ferritin is also an acute phase protein, so a serum ferritin could be normal with underlying iron deficiency in the context of inflammation - Low serum ferritin = **always** low RES iron - Normal serum ferritin doesn't always mean normal iron store levels

Answer 35

- There is no excretory pathway for iron - Daily iron requirements: 1-2mg/day (more in women to compensate for pregnancy and menstruation) Hepcidin: the iron absorption regulator - Regulates iron absorption, which would then bind to Tf and taken to tissues expressing Tf receptor - Hepcidin reduces the amount of iron in plasma by binding to and degrading ferroportin (a transmembrane protein that transports iron from inside to outside the cell) - It reduces iron absorption at enterocyte and decreases iron release from RES - Once iron absorbed, bound to Tf and taken to tissues expresing Tf-receptor - RBCs circulate for 120 days, broken down by macrophages (RES) and stored ferritin/haemosiderin - This can be released when needed and bound to Tf

Answer 36

- Hepcidin: regulates iron absorption - 'Low iron' hormone: it reduces amount of absorbed iron at the enterocyte by binding to and degrading ferroportin (transmembrane protein transporting iron from inside to outside the cell) - Hepcidin also reduces iron release from RES Synthesis: liver (requires HFE expression)

Answer 37

Hereditary haemochromatosis - All the iron from the intestines is absorbed - Due to altered HFE expression

Answer 38

Regulates iron absorption at the enterocyte - Binds to and degrade ferroportin to reduce iron absorption ('low iron' hormone) - Reduces iron release from RES - Synthesised in hepatocytes, which requires HFE expression

Answer 39

- Iron deficiency anaemia (IDA): not enough haem - Thalassaemia: not enough globin - Anaemia of chronic disease - Sideroblastic anaemia

Answer 40

Definition - The body doesn't produce enough erythrocytes and haem (made on iron) because there is not enough iron - Gradual onset Aetiology - Dietary (rare): usually premature neonates adolescent females - Malabsorption (usually due to small bowel disease) - Blood loss

Answer 41

- Blood smear: Hypochromic and microcytic erythrocytes - Tf saturation: \<15% (liver senses less iron so produces more Tf so saturations fall Low MCV and MCH levels on FBC - MCV: Mean Corpuscle Volume (ave. size of RBC) - would correspond to microcytic RBC on blood smear - MHC: Mean Cell Haemoglobin - would correspond to hypochromic RBC on blood smear Low or normal serum ferritin - **Low serum ferritin will confirm an IDA diagnosis** - Low serum ferritin always means low RES iron stores - Serum ferritin could be normal with low RES iron stores in context of tissue inflammation (or rheumatoid arthritis / IBD) as it's an acute phase protein and will be abnormally high for RES iron stores

Answer 42

Symptoms - Fatigue, SOB, Palpitations, Pallor Signs - Pallor - Koilonychia: spoon-shaped nails - Atrophic glossitis: smooth, pale, painless tongue Angular stomatitis: small cracks ay the side of the mouth - Oesophageal web: leads to trouble swallowing

Answer 43

- IDA in males and post-menopausal women: GI blood loss until proven otherwise - Young women: menstrual blood loss +/- pregnancy (only undergo GI investigations if presence of GI symptoms or blood in stool)

Answer 44

Blood: microcytic, hypochromic RBCs Likely diagnosis: Iron deficiency anaemia (IDA) Confirm diagnosis: serum ferritin Likely cause: GI blood loss - Golden rule: GI blood loss until proven otherwise - Duodenal ulcer: usually causes gastric symptoms - Diverticulosis: usually associated with rapid pellet stool (upsets bowel habit) - Stricture in right sigmoid junction: would be painful and cause constipation/diarrhoea - **Caecal carcinoma**: asymptomatic, faeces is fluid so no disruption of bowel habit

Answer 45

- **Iron replacement** Oral Replacement Ferrous sulfate or ferrous gluconate IV Replacement - IV iron: 1g over 2-3 hours - Only used as a last resort and can have serious consequences - Used if intolerant to oral iron, poor compliance, renal anaemia and erythropoeitin (Epo) replacement

Answer 46

Produced in kidneys - Produced in response to low blood oxygen levels (hypoxaemia) - It's taken to the bone marrow to stimulate stem cells to differentiate into erythrocytes

Answer 47

Def: Anaemia due to an inflammation-mediated reduction in erythrocyte production and sometimes survival (i.e. shortened life-span) - Failure of iron utilisation - Commonly found in acute and chronic infections, autoimmune disorders, after major trauma and surgery - Inflammation - Infection - Neoplasia

Answer 48

Pathogenesis - RES iron blockade: iron trapped in macrophages and raised Hepcidin - Reduced Epo repsonse - Depressed marrow activity Laboratory Findings - MCV/MCH: normal/low (Therefore either normocytic/normochromic or microcytic/hypochromic blood smear) - ESR (inflammation marker): High - Ferritin: Normal/high (i.e. high RES stores) - Serum Iron: low - TIBC (Tf measurement): low - Tf saturation: normal/low - Blood smear: RBC rouleaux (looks like a stack of coins) due to ESR - Low absolute reticuocyte count Treatment - Treat the underlying disorder

Answer 49

- They're required for DNA synthesis - Folate or B12 deficiencies would affect all rapidly growing, DNA synthesising cells (bone marrow, spithelial surfaces e.g. stomach, mouth, SI, female GUT)

Answer 50

B12 - Well stored: ast 3/4 years, so takes a long time for deficiencies to occur - B12 only absorbed in the terminal ileum - To be absorbed, it is bound to intrinsic factor (from parietal cells) - Daily intake of normal western diet (15-30ug/day) outweighs requirement (1ug/day) - small daily requirements Folate - Absorption occurs in the small bowel (200-400ug/day) - No carrier molecule required - Poorly stored: only lasts a few weeks and used quickly, therefore lhigh daily requirements

Answer 51

Pernicious anaemia - Autoimmune disease with antibodies directed at intrinsic factor found in parietal cells - Therefore, loss of transporter molecule Low B12 in plasma - Pregnancy - Hormone contraceptives - Metformin and PPIs

Answer 52

Dietary - Extensive small bowel disease (where folate is absorbed) e.g. severe Crohn's or coeliac disease Increased cell turnover - Haemolysis - Pregnancy - Severe skin disorders

Answer 53

**Anaemia** **-** **with macrocytic RBCs and megaloblastic bone marrow** - caused by insufficient erythropoeisis - Hypercellular bone marrow so the WBC count will eventually fall Bone marrow: megaloblastic anaemia - I.e. very large, abnormal immature red blood cells - Resulting from inhibition of DNA synthesis during RBC production, therefore cell cycle cannot progress from G2 to mitosis - This leads to continuing cell growth without division (macrocytic) - Leucopenia: reduced number of WBCs - Thrombocytopenia: reduced number of platelets Macrocytic RBCs - Raised MCV - Macrocytic: larger cells therefore insufficient concentration of haemoglobin (low MCH) - Anisopoiklocytosis: variance in shape and size of RBCs

Answer 54

Symptoms of anaemia: fatigue and easy bruising Mild jaundice: ineffective erythropoeisis in marrow (RBCs are being broken more therefore more bilirubin being produced) With B12 **only** Neurological problems: nerve disturbance - Bilateral peripheral neuropathy or demyelination of posterior and pyramidal tracts of the spinal cord

Answer 55

B12 deficiencies cause neurological problems - Demyelination of posterior and pyramidal tracts of the spinal cord or bilateral peripheral neuropathy

Answer 56

Definition: RBCs that are larger than normal Causes: - B12 and folate deficiencies - Reticulocytosis - Cell wall abnormalities e.g. alcohol, liver disease - Bone marrow failure syndromes i.e. myelodysplastic syndromes

Answer 57

- Inherited conditions involving an abnormality in the structure of haemoglobin - Thalassaemia: relative lack of normal globin chains due to absent genes - Sickle cell disease: production of abnormal globin chains

Answer 58

Chromosome 11 - 2 Beta globin genes (one on each chromosome) - Produces gamma globin for foetal haemoglobin and beta globin (adult haemolgobin) Chromosome 16 - 4 Alpha globin genes (two on each chromosome) There are 2 copies of each chromosome so two beta globin genes and two alpha globin genes

Answer 59

Foetal haemoglobin: - F haemoglobin: 2y and 2a globin molecules After birth (Adult haemoglobin): - y production switched off and b production switched on - A haemoglobin: 2a and 2b globin molecules

Answer 60

Definition: Haemoglobinopathies due to lack of normal globin production due to lack of globin genes Alpha Thalassaemia - Normal: inherit 4 alpha genes (2 from each parent) - Mutation: missing alpha genes e.g. could inherit 2 genes from mother and 1 from mother so missing one alpha gene Beta Thalassaemia - Normal: inherit 2 beta genes (1 from each parent) - Mutation: Missing beta genes and is more of an issue as we only have 2 beta genes

Answer 61

Missing one alpha gene - Mild microcytosis (small RBC therefore low MCV vaule) Missing 2 genes - Microcytosis, decreased RBC count, mild asymptomatic anaemia Missing 3 genes: Haemoglobin H Diseases (HbH disease) - Lack of alpha chains = relative excess beta chains which bind together (rather than with alpha globin) to produce H haemoglobin - RBCs: severely hypochromic, microcytic and mis-shapen - Splenomegaly, anaemia and fatigue - Blood transfusion independent condition unless periods of stress e.g. infection, as Hb levels drop Missing 4 genes: Hydrops foetalis - Incompatible with life

Answer 62

Missing 1 beta gene: Beta Thalassaemia Triat - Mild microcytosis Missing 2 genes: Beta Thalassaemia Major - Autosomal recessive - Unable to make HbA (adult haemoglobin) - Microcytic, mis-shapen RBCs - Significant dyserythropoiesis (defective RBC development): BM works hard to produce RBCs (fails to do so) so get expansion of both the bone marrow and bone: cellular but ineffective BM = **get frontal bossing** - Transfusion dependent anaemia from 2yrs (problem: will develop iron overload and toxicity so need iron chelators to remove iron in urine)

Answer 63

Sickle cell disease: haemoglobinopathy caused by production of abnormal globin chains due to abnormal globin genes Two types: - Hb SS: more severe with two copies of sickle cell haemoglobin - Hb SC: less severe

Answer 64

- A mutation in the B-globin gene on Chromosome 11 resulting in HbS (sickle haemoglobin) production - Sickle haemoglobin (HbS) = 2 alpha and 2 beta (sickle) chains - Problem: in low oxygen states, Hbs polymerises and with continual polymerisation the RBCs will sickle (become moon shaped) - Rate of of polymerisation depends on: deoxygenation rate and Hb concentration

Answer 65

- Reduced RBC survival: haemolysis (haemolytic anaemia) - Episodes of pain (sickle crises) which can occur in many places (pain usually in hands, feet or breastbone/ribs), and are caused by occlusion of small blood vessels when RBCs sickle (in low oxygen states) - Occlusion of vessels can also lead to infarction Infarction can occur in many systems: - Brain (stroke), lungs (pulmonary HTN), bones (dactylitis - swelling of a digit), spleen (hyposplenic), eyes (vascular retinopathy)

Answer 66

Diagnosis: blood spot test for newborns Treatment: 1. Prevent crisis - Hydration, analgesia, early intervention - Prophylactic vaccines and Abx: spleen is removed once sickle RBCs occlude the vessels and it starts to enlarge, therefore the patient has a reduced immune function - Folic acid: bone marrow is more active therefore higher folic acid requirements 2. Management of Crises - Oxygen, fluids, analgesia, Abx - Transfusion/Red cell exchange: reduce the amount of HbS 3. Bone marrow tranplantation: rarely

Answer 67

Definition: anaemia related to reduced RBC lifespan Congenital haemolytic anaemia - Abnormalities of RBC membrane: Hereditary spherocytosis - Haemoglobinopathies: Thalassaemia and sickle cell disease - Abnormalities of RBC enzymes: pyruvate kinase deficiency anaemia or G6P dehydrogenase deficiency anaemia (Structural abnormalities: Autosomal dominant, Enzymatic abnormalities: AR or X-linked) Acquired haemolytic anaemia - Autoimmune: warm type (IgG) and cold type (IgM) - Iso-immune: haemolytic disease of new born (HDN) - Non-immune: fragmentation haemolysis

Answer 68

- Normally: bone marrow can compensate for a reduction in RBC lifespan down to 20days - RBC lifespan \<20days: BM can no longer accomodate and anaemia develops RBC lifespan = 120d - Normal Hb RBC lifespan = 20-100d - Normal Hb, increased reticulocyte number, increased unconj. bilirubin - BM is pushing out more reticulocytes to compensate for reduced life span and patient won't be anaemic: **compensated haemolytic state** RBC lifespan \< 20d - Low Hb, increased reticulocyte number, inc. uncong. bilirubin (product of haem breakdown), splenomegaly - In chronic haemolytic states, raised bilirubin can cause pigment gall stones - **Haemolytic anaemia**

Answer 69

Congenital - Hereditary spherocytosis: abnormality of RBC membrane - Thalassaemia: reduced normal globin production - Sickle cell disease: production of abnormal globin Acquired - autoimmune haemolytic anaemia (warm and cold types) - Haemolytic disease of the newborn (HDN) - Fragmentation haemolysis

Answer 70

Hereditary spherocytosis: autosomal dominant (congenital) form of haemolytic anaemia involving abnormalities of the RBC membrane Cell changes/Blood film - RBCs = spherocytic (spherical rather than biconcave) and polychromatic (reticulocyte count has increased) - Reticulocytes are immature RBCs still containing RNA therefore stain blue Presentation - Jaundice - Splenomegaly - Pigment gallstones Treatment - Splenectomy and hyposplenic prophylaxis: Hyposplenic state can lead to serious infection therefore try to avoid

Answer 71

- Congenital haemolytic anaemia (autosomal recessive) Kinase pyruvate: needed for ATP production - Deficiency causes chronic haemolytic anaemia Glucose-6-Phosphate (G6P) dehydrogenase: helps protect against oxidative damage - Deficiency causes acute haemolytic anaemia

Answer 72

Cold AIHA v Warm AIHA Cold: Autoantibody IgM with complement Warm: Autoantibody IgG with/without complement Cold: IgM is a giant molecule with 10 binding sites, therefore causes red cells to agglutinate (stick together): seen on blood film Warm: IgG binds to RBCs and damages membranes: become spherocytic (*Autoantibodies opsonise the RBCs for phagocytosis by macrophages in the reticuolendothelial system (RES))* Cold: Usually idiopathic Warm: Causes include idiopathic, other autoimmune disease, lymphoproliferative disorder, drug induced Cold: Intravascular haemolysis i.e. RBCs lyse in the circulation releasing haemoglobin into the plasma Warm: Extravascular haemolysis i.e. RBCs opsonised by Ab and phagocytosed by RBCs in the liver and spleen

Answer 73

Blood film: RBCs are stuck together (agglutinated) due to IgM autoantibody Diagnosis with a blood film: presence of agglutinates (RBCs stuck together) Treat: harder to treat than warm AIHA. If idiopathic, keep the patient warm (hatm gloves, warm shoes)

Answer 74

Blood film: identical to hereditary spherocytosis - RBCs are spherocytic and polychromatic (reticulocytes look blue due to presence of RNA in cytoplasm) Diagnosis: Direct Coombs Test - Detects IgG autoantibody on the surface of RBCs Treatment: - Stop any medication - Start steroids (this is an AI disorder) - Immunosuppression - Splenectomy: last resort. RBCs are coated with warm autoimmune autoantibodies (IgG). The RBCs are opsonised and destroyed by macrophages of the RES, most of which are found in the spleen

Answer 75

An increased number of reticulocytes (RBC precursors) as they still contain RNA in the cytoplasm. RNA stains blue which causes difficult colours on a blood film

Answer 76

The Direct Coombs Test - Detects the presence of IgG autoantibody on the surface of RBCs How does it work? - Antibodies are added to a blood sample - These antibodies will react to the IgG on RBC surface, forming immunological lattices - The red cells will stick together: red cell agglutination A +ve result will occur with: - AIHA - HDN (Haemolytic Disease of the Newborn) - Patients with antibody on the surface of RBCs

Answer 77

Purpose: Detects IgG on the surface of RBCs How it works: Add antibodies to a blood sample. The antibodies will react to IgG on the surface of RBCs and form immunological lattices. - This will cause RBCs to stick together: RBC agglutination +ve test with: - AIHA - Haemolytic Disease of the Newborn (HDN) - A patient with antibodies on the surface of their RBCs (not necessarily AIHA)

Answer 78

Purpose: To detect RBC antibodies in plasma - Used to crossmatch a patient with a unit of blood - Testing for immune antibodies - Mix a sample from the unit of blood intended for transfusion with a sample of the patient's plasma - If there are immune antibodies: they will stick the the red cells from the blood sample of donor - Then add antibodies to detect the immune antibodies on the RBCs (i.e. Direct Coombs Test)

Answer 79

- An iso-immune haemolytic anaemia - Occurs when there is a Rhesus -ve mother, RhD+ partner and a RhD+ baby - The foetal and maternal circulations mix - RhD+ red cells of the baby escape into maternal circulation and the mother makes antobodies against RhD+ antigens - These antibodies cross the placenta and attack RBCs of the baby§

Answer 80

Size of RBCs: - Hypochromic, microcytic: IDA usually - Macrocytic: megaloblastic bone marrow (B12/folate deficiency) Are WBCs/platelets affected? - Anaemia with abnormal WBCs/platelets: likely to be a bone marrow problem Haematinic results: - Haematinic: nutritents required for normal erythropoiesis i.e. folate/B12/ferritin What does the blood film look like? - Rouleaux: ACD - Agglutinated RBCs: Cold AIHA - Polychromatic: inc. reticulocytes e.g. hereditary spherocytosis or Warm AIHA - Ringed sideroblasts

Answer 81

Lymphoma: cells tend to aggregate and form massess/tumours in lymphatic tissue Myeloma: tumour of the bone marrow and involves plasma cells that produce antibodies Leukaemia: cancerous cells circulate in the blood and bone marrow

Answer 82

Hodgkin's lymphoma (15%) Non-Hodgkin's lymphoma (85%)

Answer 83

- Commonest blood cancer - Occurs at any age - Commonest cancer in the \<30yrs

Answer 84

- Lymphadenopathy: painless, rubbery - Splenomegaly - B symptoms: systemic symptoms of unexplained fever, drenching night sweats and weight loss - Anaemia

Answer 85

- History: symptoms, duration, B symptoms - Clinical Exam: lymph nodes, splenomegaly - Blood tests: FBC etc, ESR (raised in Hodgkin's lymphoma), LDH (turnover rate, raised in aggressive lymphoma), could be normal - Imaging: CT, PETCT - BM Biopsy: taken from iliac crest

Answer 86

Stage I: single lymph nodes group involved above or below the diaphragm Stage II: more than 1 lymph node group involved on the same side of the diaphragm Stage III: lymph node group involvement on both sides of the diaphragm (inc. spleen) Stage IV: Extranodal involvement eg. liver, bone marrow A or B - A: no B symptoms, B: B symptoms present

Answer 87

- Type and stage of lymphoma - Age, performance status - Co-morbidities - Patient preference

Answer 88

B Cell (\>90%): - Follicular lymphoma (indolent) - Diffuse Large B cell lymphoma (aggressive) T Cell: - Aggressive or indolent

Answer 89

- Indolent (low-grade) B-cell lymphoma - CD20 antigen expressed on B-lymphcytes (target for the monoclonal antibody Rituximab) - Resembles normal germinal centres (where B cells proliferate) - Characterised by translocations involving BCL2 gene - Slow growth but reduced apoptosis

Answer 90

- Usually presents with stage 4 (advanced) disease as they are slow growing and don't cause many symptoms - Median age: 65yrs - B symptoms less common - Indolent: causing little/no pain - Usually incurable as diagnosed at such a late stage

Answer 91

As most present at advanced disease, treatment aimed at alleviating symptoms rather than cure Early stage: 1A/2A: localised radiotherapy, curable Advanced stage: - Asymptomatic, no bulk, no end organ damage: watch and wait - Symptomatic +/or organ compromise: immunochemotherapy - Rituximab (anti CD20 monoclonal Ab) and chemo Very responsive to tratment but there's a tendancy to relapse

Answer 92

- Agressive/High grade B-cell lymphoma - Resembles activated B-cells: large, multinucleated cells - CD20 antigen expressed on B-lymphocytes (Rituximab target) - High proliferation fraction, variable rate of cell death - Most common NHL subtype

Answer 93

- Lymphadenopathy: usually rapidly enarging LN mass - B symptoms - Extra-nodal presentation: Waldeyer's ring, GI tract, skin, bone, CNS - Agressive but curable in \>50%

Answer 94

- Agressive chemotherapy with **intention to cure** - Variable response Early (Stage 1A): R-CHOP (chemo) x3 and radiotherapy - All other stages: R-CHOP x6 R-CHOP Chemotherapy - Rituximab - Cyclophosphamide - H: Adriamycin - O: Vincristine - Prednisolone Given on day 1 of 21 day cycle

Answer 95

- Very high-grade B-cell lymphoma - Resembles proliferating germinal centre cells - Very high proliferation rate and high rates of apoptosis - Marked B symptoms, massive tumour bulk and extra-nodal disease - Treat with intensive chemotherapy

Answer 96

Classical (\>90%) - Nodular sclerosing - Mixed cellularity - Lymphocyte rich - Lymphocyte depleted Nodular lymphocyte predominant

Answer 97

Peak incidence: 20-24yr olds, second peak in 70-79yr olds Other RF: male Most common: nodular sclerosing and mixed cellularity

Answer 98

- High grade lymphoma with prominent component of reactive cells - Neoplastic cells resemble atypical activated B-cells - Characterised by strong CD30 expression and loss of some B-cell antigens Malignant cell: **Reed-Sternberg cell** - Giant cells, mono-/binucleated - This is the differentiating cell between Hodgkin's and non-Hodgkin's lymphoma (ie. no Reed-Sternberg cell: classified as non-Hodgkin's) - These are mixed with neutrophils, lymphocytes, macrophages

Answer 99

Presence of the Reed-Sternberg cell in Hodgkin's lymphoma

Answer 100

- Painless lymphadenopathy: usually a neck lump with associated cough and SOB - Spreads to adjacent lymph nodes than haematogenous spread to liver, lungs and bone marrow - May have B symptoms - Itch - Alcohol related pain - May present with CXR mass (usually neck)

Answer 101

A core biopsy or excision node biopsy

Answer 102

- High cure rate (\>90%) Early stage: chemotherapy followed by radiotherapy Advanced: intensive chemotherapy Chemotherapy: ABVD Adriamycin Bleomycin Vinblastine Dacarbazine

Answer 103

A tumour of plasma cells in the bone marrow which are part of the immune function and release antibodies

Answer 104

- Neoplastic cells resemble normal plasma cells - Typically the nucleus is to one side and basophilic cytoplasm Abnormal plasma cells will produce abnormal antibodies called paraproteins - Usually see IgG and IgA - Light chain myeloma: only part of the immunoglobulin is produced - Non-secretory myeloma: no Ig produced

Answer 105

Majority of cases have non-specific symptoms - Backache, rib pain - Fatigue - symptoms from hypercalaemia (due to bony erosion) - recurrent infection - renal impairment

Answer 106

Classical triad 1. Increased plasma cells in bone marrow 2. Clonal immunoglobulin or paraprotein 3. Lytic bone lesions (bone damage caused by build up of cancerous plasma cells)

Answer 107

Blood tests - ESR: \>100 - FBC, Ca, U&Es - SFLC (serum free light chain) quantity Blood film - Rouleaux: coin stacking of red cells - Blue-ish background due to rise in protein Urine Tests: look for light chains in urine Bone marrow aspirate: excess plasma cells Imaging: MRI goos for identifying lytic lesions - Numerous lytic lesions scattered throughout skull: pepperpot skull

Answer 108

Rouleaux RBCs (stacking) Blue-ish background due to increased protein (immunoglobulins)

Answer 109

Neoplastic plasma cells in BM \>10% of total cells with one of the following - Evidence of end-organ damage attributable to plasma cell prolif (CRAB): hyper**c**alaemia, **r**enal insufficiency, **a**naemia, **b**one lesion - Biomarker of malignancy: clonal plasma cell % \>=60%, serum free light chain ratio \>=100, \>1 focal lesion on MRI

Answer 110

Only treat the symptomatic - **Bone marrow transplant**

Answer 111

Blood cancer resulting in the accumulation of abnormal leucocytes (WBCs) in bone marrow +/- blood +/- other tissues

Answer 112

Acute - Acute myeloid leukaemia (AML) - Acute lymphoid leukaemia (ALL) Chronic - Chronic myeloid leukaemia (CML): *can turn into acute leukaemia (AML or ALL)* - Chronic lymphoid leukaemia (CLL): *can transform into a high-grade lymphoma*

Answer 113

Bone marrow failure

Answer 114

**Acute:** symptoms due to bone marrow failure **Chronic:** symptoms due to accumulation of cells **Acute:** presents with florrid marrow failure, taking over the marrow quickly causing bruising, fatigue, pancytopenia **Chronic:** don't get marrow failure to same degree with non-specific symptoms eg. weight loss, night sweats. High WBC counts in the blood **Acute:** Arises over a couple of weeks and will probably kill you quickly **Chronic:** Presents over a couple of months and may kill you slowly

Answer 115

Lymphoid: tumour of T and B lymphocytes (related to the lymphatic system) Myeloid: everything else ie. neutrophils, basophils, monocytes, eosinophils etc. (related to the bone marrow)

Answer 116

When it arises from a pre-existing bone marrow condition: - myeloproliferative disorders (MPD) - myodysplastic syndromes (MDS)

Answer 117

Clonal disorders: neoplastic malignant cells derived from a single ancestor Blastic proliferation in bone marrow: maturation arrest ie. blast cells look primative and not maturing so expand and encroach on the bone marrow Rapid onset Serious compromise of normal marrow Death within days-weeks if untreated

Answer 118

Usually idiopathic Chemical Chemotherapy Radiotherapy Genetics eg. Down's syndrome, Fanconi syndrome MDS MPD

Answer 119

Rapid onset of symptoms Lymphadenopathy (accumulation of WBCs in the lymph nodes) Legarthy (anaemia) infection (neutropenia) bleeding and bruising inc. purpuric rash (thrombocytopenia) bone pain gum swelling, mouth ulcers

Answer 120

anaemia neutropenia thrombocytopenia blast cells present (as well as excess blast cells seen in BM)

Answer 121

**Blast cells \>20% of the bone marrow**

Answer 122

- Can look for CD20 antigens - can type leukaemias quickly and accurately - essential to determine prognosis - allows decisions to be made on management

Answer 123

secondary AML (to MDS/MPD) relapsed AML Elderly patients Refractor to induction ie. no response to first line chemo

Answer 124

1. Intensive chemotherapy +/- stem cell transplant - Used for patients \<60 - 5yr survival: 50% 2. Low dose chemotherapy - For patients 60-65 - 5yr survival: \<10% 3. Supportive care only - Older patients with major co-morbidities and a median survival 4-6 months

Answer 125

- Aims to eradicate the abnormal clone Complications: - Bleeding and infection worsens with treatment - Hair loss, sterility, mucositis - Prolonged inpatient stays - Psychological element

Answer 126

Age group: mostly seen in kids Clinical Presentation - limping child: bone pain - purpuric rash (thrombocytopenic rash) - unexplained, severe bone pains

Answer 127

Chemotherapy - CNS directed treatment is essential to prevent relapse

Answer 128

Blood transfusions: symptomatic patients, improves quality of life Fresh frozen plasma (FFP): - For coagulopathy/disseminated intravascular coagulation (DIC: blood clots form throughout the body) Platelet transfusion: - Purpura and bleeding Abx Growth factors (prevent risk of infection)

Answer 129

Patients: - younger, healthier patients - relapsed patients - refractory patients - age \<60 Transplant used: allogenic - HLA matched stem cells - NB GvHD and GvL: donor immune system is what cures the patient but will also attack patient's normal cells and so **need a balance**

Answer 130

Epidemiology: - incidence rises with age (median is 67yrs) - male Aetiology: idiopathic

Answer 131

Presentation: - None (75% incidental findings) - B symptoms (night sweats, weight loss, legarthy) - Anaemia symptoms - Lymphadenopathy (excess WBCs accumulate in lymph nodes) - Infection (neutropenia) Diagnosis: - Incidental finding - FBC shows isolated lymphocytosis (elevated lymphocyte numbers): seeing this in an older, fit person is almost always CLL until proven otherwise **- Diagnosed by flow cytology: clonal B-lymphocyte population \>5x10⁹/L**

Answer 132

Hypogammaglobinaemia: may need globin replacement Cell mediated immunity impaired - T-lymphopenia - Neutropenia - Defects in complement activation Pulmonary infection is common

Answer 133

Symptoms: - B symptoms, symptomatic nodes Bone marrow failure: - anaemia, thrombocytopenia, neutropenia * Do not treat the asymptomatic*

Answer 134

- Asymptomatic (20-50%) - B symptoms - Abdominal discomfort - Splenomegaly in 50-70%

Answer 135

CLL: 17p deletions resulting in loss of p53 CML: gene translocation of Bcr-Abl gene (the bcr-abl protein produced changes the behaviour of the cell)

Answer 136

Diagnosis; - blood film and clinical features - molecular testing: bcr-abl on PCR or FISH - **if Bcr-abl negative: not CML** Treatment; - **imatinib:** blocks bcr-abl phosphorylation of these targets

Answer 137

O- : universal donor AB+ : universal recipient

Answer 138

ABCDE Resuscitation - Access - Fluids (replace what's being lost) - Blood products - Transexamic acid: a fibrinolysis inhibitor (helps clots that form to remain establisted) If still in shock due to blood loss: **- Major haemorrhage protocol: RBCs, FFP, platelets and cryoll (rich source of fibrinogen)**

Answer 139

1. Take baseline blood samples before transfusion for - FBC, U&Es, LFTs, Ca, group and save, clotting screen including fibrinogen 2. If trauma and \<3hr from injury, give transexamic acid 3. Gain IV access, do ABC and give oxygen 3. Use O- until patient group is known and use group-specific blood as soon as possible. Also give FFP and platelets If bleeding continues: - If no lab results available: give further FFP, cryoll and platelets - If lab results known: red cells if falling Hb, FFP if PT ratio \>1.5, cyroll if low fibrinogen and platelets if low platelets

Answer 140

- Loss of more than one blood volume within 24hours (around 70ml/kg, \>5l in a 70kg adult) - 50% of total blood volume lost in less than 3 hours - Bleeding in excess of 150ml/min

Answer 141

Haemorrhagic shock: - more bleeding, less circulating volume, lower CO, less oxygen delivery, less tissue perfusion - hypothermia: *use warmer blood, keep patint warm, foil hat, monitor temp* - acidosis: *monitor with blood gases* - coagulopathy: *Give platelets, FFP, cryoll* - hypocalcaemia: *replace if low levels on blood gas*

Answer 142

Required: - Functioning platelets - Functioning endothelium - Coagulation factors Imbalance: - Thrombosis or bleeding

Answer 143

Laceration damages the blood vessels and disrupts endothelium Exposure of: - tissue factor and collagen - Von Willebrand Factor (VWF - promotes platelet aggregation) binds to collagen when it's exposed 1. Stimulates primary haemostasis: - Recruitment and adhesion of platelets (bind to VWF) - The binding activates the platelets and they release granular contents, attracting more platelets, activating them etc. - Activation of platelets also leads to exposure of phospholipids - this forms a platelet plug 2. Stimulates secondary haemostasis: - activation of coagulation factors * Primary and secondary haemostasis occur simultaneously*

Answer 144

Initiation: extrinsic pathway - Produces small amounts of thrombin (IIa) from prothrombin (II) - Thrombin also activated F VIII, which cross-links fibrin and strengthens it Propagation: intrinsic pathway - Comes from the small amount of thrombin produced in initiation and propagates the whole system - Thrombin with F IX activates XIII - XIIIa and IXa propagate prothrombinase complex Thrombin generation and fibrin production Regulation: - Need balance between coagulation and anticoagulation factors - Initiation and propagation need regulated - Anti-thrombin III: down-regulates prothrombin and almost all coag factors - When thrombin is made, it binds to a thrombomodulin receptor which is an important feedback mechanism Fibrinolysis - Need to be able to breakdown the fibrin clot when wound is healing - Plasminogen is converted to plasmin - Plasmin degrades cross-linked fibrin into fibrin degradation products - Self-regulation: fibrin stimulates production of plasminogen activators

Answer 145

- FBC (platelet count) - Platelet functionality: light transmission aggregometry

Answer 146

Prothrombin Time (PT): extrinsic pathway - Extrinsic: Factors VII - Common: X, V, II and fibrinogen Activated Partial Thromboplastin Time (APTT): intrinsic pathway - Intrinsic: XIII, IX, XI, XII - Common: X, V, II and fibrinogen Thrombin clotting time (TCT) - Measurement of how much fibrinogen is in the blood to be comverted into the fibrin clot - Dependent on levels of fibrinogen and how well the fibrinogen functions

Answer 147

Anticoagulants: inhibit one or several components of the coagulation cascade - Warfarin, rivaroxaban, apixaban, dabigatran, Heparin Fibrinolytic agents: enhance lysis of fibrin clot Anti-platelet agents: inhibit platelet activation or aggregation - Aspirin, Clopidogrel

Answer 148

Warfarin: Vit K antagonist, so factors II, VII, IX, X Heparin: stimulates anti-thrombin III that directly inhibits activation of prothrombin Dabigatran: thrombin Apixaban and rivaroxaban: Xa

Answer 149

Indication: - Treatment and prophylaxis for thromboembolic events: immediate anticoag effect for acute DVT/PE and prophylaxis against VTE - Renal dialysis - Acute coronary syndrome treatment Action: - Enhances the activity of antithrombin III - Antithrombin III inhibits thrombin - Heparin also inhibits other factors in the coagulation cascade inc. factor Xa - Produces an anticoagulant effect

Answer 150

- Delayed onset and onset: 3-4 days before any level of coagulation, 4-5 more days to reach steady state, and 3 days for anti-coagulant effect to wear off - Effective T 1/2 (36hours) - Narrow therapeutic window: low INR means it's ineffective, too high means high bleeding risk - Many drug and food interactions - **Not for immediate anticoagulation or short-term thromboprophylaxis**

Answer 151

Warfarin: slow onset, slow offset resulting in smooth anticoagulation DOACs: Rapid onset and offset Warfarin: requires INR monitoring DOACs: requires annual review Warfarin: Many drug and food (inc. alcohol) interactions DOACs: few drug and no food/alcohol interactions Warfarin: renal impairment may inc. bleed risk DOACs: renal impairment may be a contra-indication Warfarin: rapid reversal with vit. K DOACs: no rapid reversal agent

Answer 152

Kinases - Streptokinase, urokinase Tissue plasminogen activators (tPA) - Alteplase, tenecteplase

Answer 153

Class: tissue plasminogen activators (tPA) Indication: - acute ischaemic stroke within 4.5 hours of onset - myocardial infarction within 12 hours of onset - massive pulmonary embolism Action: - recombinant form of tissue plasminogen activator - catalyses the conversion of plasminogen to plasmin - promotes fibrin clot lysis

Answer 154

Drugs: - tissue plasminogen activators (tPA): alteplase and tenecteplase - kinases: urokinase and streptokinase Pros: - Smaller doses- Administered directly into the vessel containing thrombosis Uses: - Acute limb ischaemia - Massive DVT - Blocked CVC (central venous catheters)

Answer 155

Class: anti-platelet drug Indication: - secondary prevention of thromboembolic events Action: - Irreversibly blocks the ADP receptor on the platelet cell membrane - This inhibits the formation of GPIIb/IIIa complexes, needed for platelet aggregation - Reduced platelet aggregation and thrombus formation

Answer 156

Class: anti-platelet drug Indication: - secondary prevention of thrombotic events - Pain relief Action: - Irreversible inactivation of the cyclo-oxygenase enzyme (COX-2) - This reduces platelet thromboxane production and endothelial prostaglandin production: - Reduced thromboxane production: reduced platelet aggregation and thrombus formation - Reduced prostaglandin production: reduced nociceptive sensitisation and inflammation

Answer 157

- CV disease - Acute MI - Secondary prevention of CVD - Acute stroke/TIA/secondary prevention - Peripheral vascular disease

Answer 158

DIC is a acquired, consumptive process characterised by systemic activation of coagulation, resulting in the generation and deposition of fibrin, leading to microvascular thrombi formation in various organs Pathophysiology: - Haemostasis is out of control with over-activation of the coag cascade - This leads to the formation of many micrsovascular thrombi - Eventually, there is exhaustion of the coag cascade due to consumption of coag factors and platelets - This leads to bleeding even with slight blood vessel damage - Can result in life-threatening haemorrhage Patients have both thrombi and haemorrhage

Answer 159

*DIC due to the release of pro-coagulants eg. TF and bacterial components* Sepsis Malignancy Massive haemorrhage Severe trauma Pregnancy complications eg. pre-eclampsia

Answer 160

Bleeding: bruising, mucous bleeding (eg. gums), needle placement Blood in urine and stool Chest pain, SOB Confusion Headache Low BP

Answer 161

Platelets: low Fibrinogen: low PT: prolonged APTT: prolonged D-Dimer: marker of clotting

Answer 162

- Treat underlying cause - FFP +/- platelets in bleeding or high-risk of bleeding - Organ support: ventilator, haemodynamic, transfusions

Answer 163

- Haemorrhage - Longer clotting time affecting both intrinsic and extrinsic pathways or common pathway **Over-coagulationg with warfarin** - Warfain affects F II, VII, IX, X therefore mainly affects prothrombin time

Answer 164

1. Stop warfarin or reduce dose 2. Give Vit K (oral or IV): rapid reversal 3. Give coag factors (II, VII, IX, X): reverses warfarin effect within 30mins

Answer 165

- poor coagulation for synthesis in the liver - disseminated intravascular coagulation - hypersplenism - reduced thrombopoietin synthesis

Answer 166

APTT = prolonged - Isolated prolonged APTT means defect in the intrinsic pathway (F VIII, IV, XI) - Factors VIII and IX deficiencies are more serious and associated with Haemophilia Likely diagnosis: Haemophilia A

Answer 167

Pathology: - Factor VIII deficiency: impairs the body's ability to make blood clots - X-linked recessive (men affected, women are carriers) Clinical features: - bleeding for a prolonged time after injury - easy brusiing - bleding inside joints (haemarthroses) - delayed bleeding Lab: isolated prolonged APTT

Answer 168

- Education: remember to tell doctors - Desmopressin: boost's body's own factor VIII, but won't work if patient cannot make any factor VIII - Replacement therapy in severe Haemophilia

Answer 169

- Mucosal bleeding: uterus and nasal mucosa - No petechaie: petechaie suggest problem with primary haemostasis ie. platelets - Factor VIII is low Differetials: - Haemophilia A - Von Willebrand Disease

Answer 170

- facilitates platelet aggregation and adhesion in primary haemostasis - binds factor VIII and prolongs it's T 1/2 in plasma (influences secondary haemostasis)

Answer 171

= A genetic disorder caused by lack of or defective Von Willebrand Factor - Mild bleeding disorder Inheritance: autosomal dominant with variable penetrance Characterisation: - Mucosal bleeding - Reduced VWF with/without reduced platelet aggregation (prolonged PT) with/without reduced F VIII (prolonged APTT)

Answer 172

Inherited thrombophilia (the tendancy to form thromboses)

Answer 173

= Tendancy to form thromboses Causes: deficiencies of natural anticoagulants (regulators of the coagulation cascade) - Antithrombin - Protein C - Protein S

Answer 174

mix equal amounts of the patient's plasma with normal plasma - If deficiency of a factor from extrinsic pathway: VIII, IX, XI, XII, mixing with normal plasma should fix the problem - If it is still prolonged: suggests the presence of an inhibitor causing the prolonged APTT

Answer 175

- Lupus anticoagulant = phospholipid dependent antibody - interferes with phospholipid dependent tests ie. APTT - if persistent, may be associated with prothrombotic state

Haematology Flashcards

(202 cards)