Haematology Flashcards

Question

What are some causes of Normocytic Anaemias?

Answer 1

- Blood loss - Chronic diseases - cytokines decrease effect of EPO on red cells - Renal failure, decreased EPO production - other acute reasons ( usually in 20's)

Answer 2

- Iron deficiency - Thalassaemia

Answer 3

- Large RBC with no DNA involvement - Alcohol - Liver Disease

Answer 4

- Large RBC with DNA affected - B12 & Folate deficiency - Chemotherapy - AZT ( HIV treatment)

Answer 5

- weight loss - fatigue - Glossitis (swollen tongue) - jaundice - dementia - paraesthesia - neuropathy

Answer 6

variation in RBC shape

Answer 7

Variation in RBC size

Answer 8

- responding anaemia or post-transfusion, where there is a variety of different RBCs

Answer 9

Low platelets due to \> Decreased production - Congenital (rare) - Acquired: BM damage due to drugs, Alchohol, Blood malignancy \> Increased destruction - Congenital ( from maternal antibodies) - Aquired: ITP (idiopathic), Infections, drug-induced

Answer 10

- during infections, Myeloproliferative disorders (MPD), Leukemias

Answer 11

- Acute infection - dark granulated cytoplasm

Answer 12

- Severe Infections - Leukemias - BM

Answer 13

- Megaloblastic conditions - B12 & Folic acid deficiency - multilobular in appearance

Answer 14

- higher than normal lymphocyte levels in an FBC or in a blood film Presents in - Viral infections: measles, chickenpox, IM - Some bacterial infections - Stress-related: Post MI - Vigorous exercise - smoking - LPD's i.e CLL (chronic lymphatic leukaemia)

Answer 15

- Lower than normal lymphocyte levels in an FBC or a blood film Presents - Acute stress: surgery/ trauma - Acute/ Chronic Renal Failure - Carcinoma - AIDS/HIV - Cytotoxic therapy - Some inherited: SCID (severe combined immunodeficiency )

Answer 16

- higher than normal neutrophil levels in an FBC or blood film Presents - Acute/ chronic bacterial infections - a few viral, fungal and artistic infections - Tissue damage - Inflammation (UC, RA?) - Malignant dx - MPD and leukaemias - Cytokines (Granulocyte-Colony Stimulating Factor) - Drugs: Corticosteroids, lithium

Answer 17

- lower than normal neutrophil levels in an FBC or blood film Presents - Bacterial infection and some viral, fungal parasitic infections - Anti-cancer drugs - Irradiation - BM replacement with Ca - Aplastic anaemia - Autoimmune neutropenia: associated with dx - Inherited (rare): Chediak Higashi syndrome (child hood)

Answer 18

- Bleeding- main one - Deficiency, iron, B12, folic acid - Haemolytic - Bone Marrow Dysfunction/ infiltration - poor O2 utilisation/loading

Answer 19

110-160 g/L

Answer 20

115-165 g/L

Answer 21

110-160 g/L

Answer 22

130-180 g/L

Answer 23

- Pallor, pale conjunctiva - Tachypnoea - Tachycardia - Koilonychia

Answer 24

- Serum Ferritin - Serum Iron - Serum Transferrin - % Transferrin Saturation

Answer 25

- 4 alpha haemoglobin genes - 2 beta haemoglobin genes

Answer 26

- shortness of breath - headaches - tiredness - palpitations - pale conjunctiva - tachypnoea

Answer 27

- sternum - vertebrae - pelvis - femur

Answer 28

100 mcg/day - 4 times that amount in women

Answer 29

- Serum Ferritin - Serum Iron, labile - Serum Transferrin - % Transferrin saturation

Answer 30

- carrier molecule of iron - increases if iron is deficient - similar to total iron binding capacity

Answer 31

- storage form of iron

Answer 32

- bleeding via menstruation, occult GI malignancy - GI peptic ulcer - increased requirements

Answer 33

Erythropoietin - production of new RBC - levels are often higher when patient is anaemic

Answer 34

- Iron deficiency - Inherited disorders of haemoglobin

Answer 35

- B12 or folate deficient- production of nucleotides - myelodysplasia

Answer 36

- aneamia of a chronic disease - acute haemorrhage Renal failure

Answer 37

- new RBC, still have their RNA within them- flow cytometry - indicates the rate of RBC production by the marrow -

Answer 38

it is an erythrocyte (RBC) precursor, still contains mRNA

Answer 39

7-8 microns

Answer 40

- chromatin is out of phase with DNA replication - very large megaloblasts

Answer 41

- low ferritin - low Fe - high transferrin - low transferrin saturation

Answer 42

- normal ferritin - abnormal Hb electrophoresis/HPLC

Answer 43

- being vegan - gastric surgery - Crohn's disease - lack of intrinsic factor --> leading to inadequate absorption

Answer 44

- lack of folate in the diet - malabsorption (coeliac) - excess utilisation

Answer 45

- normocytic cells - normal/ raised ferritin, normal/low transferrin - raised hepcidin and inflammatory proteins

Answer 46

- Iron trapped inside macrophages - cancer - inflammation - rheumatoid arthritis - renal failure

Answer 47

- lack of erythropoietin (low serum EPO ) - red cell horomone produced by kidney

Answer 48

- with weekly sc injections of recombinant EPO

Answer 49

- spherical red cells, not biconcave - e.g hereditary spherocytosis, hereditary elliptocytosis - a splenectomy can help

Answer 50

- Hb electrophoresis

Answer 51

- microcytic hypochromic blood film - low MCV

Answer 52

- Autoimmune: warm IgG vs. cold IgM - Alloimmune: red cell transfusion reaction

Answer 53

- mechanical heart valves can destroy RBC - DIC, very sick patients: spesis metastatic cancer - MAHA: microangiopathic haemolytic anaemia

Answer 54

- high bilirubin levels - patients are jaundiced, may need to check nails and mucous membranes - blood film to check for spherocytes - high LDH levels - high reticulocyte count - low haptoglobins

Answer 55

- It is a bleeding condition due to a factor XI deficiency (the Intrinsic pathway) - it is commonly found in Jewish populations - and is Autosomal recessive

Answer 56

- when there is a clot in the deep vein of your legs,

Answer 57

- ADP: activate platelets further - Serotonin: vasoconstriction - Thromboxane A2 (TxA2): vasoconstriction and aggregation - Calcium and presence of phospholipids: allows coagulation reactions

Answer 58

- Extrinsic (tissue factor) pathway: involves tissue factor - Intrinsic (contact activation) pathway: thrombin, factor XIIa, a nucleation site, glass in a laboratory

Answer 59

- Prothrombin --\> Thrombin: converts fibrinogen into fibrin - Factor XIIIa, cross-links it into a clot

Answer 60

- factor XI - factotor XII - factor IXa

Answer 61

- necessary for the production of Ca-dependent proteases in the liver - i.e factor II, VII, IX, X (extrinsic tissue factor pathway)

Answer 62

- lack of bile salts, if exogenous lipids were not being properly digested - Warfarin toxicity: prevents recycling of vitK

Answer 63

- a mutation in the factor VIII gene - X-linked recessive disease

Answer 64

- X-linked recessive - a mutation in the factor IX gene

Answer 65

- formation of a haemostatic plug physically protects and coats the surface of the injury initially: platelet adhesion, activation and aggregation - coagulation - vasoconstriction: decreases local blood flow

Answer 66

- aggregate at the site of injury, over fibrinogen, forming a haemostatic plug - contribute to vasoconstriction by releasing vasoconstrictor compounds, serotonin TxA2 - secrete/provide compounds that encourage coagulation, including the phospholipids

Answer 67

- B cells - T helper cells - NK cells - Plasma cells

Answer 68

- eosinophils - monocytes/macrophages - neutrophils - RBC

Answer 69

- change dramatically in response from ADP or exposed collagen - more spindly shape - metabolism goes up - exocytose many granules - their membranes gain proteins (GP2b/3a) - many reactions of the clotting cascade can only take place on the membrane of an activated platelet - platelet aggregation can only occur on the surface of already activated platelets

Answer 70

- Fibrinolysis. - Anticoagulation factors. - Maintaining platelets in the inactivated state. - Keeping coagulation initiation signals sequestered (eg Factor III/Tissue factor behind the endothelium). - Rapid blood flow

Answer 71

- Factor Xa is an activated enzyme. It catalyses the conversion of prothrombin (factor II) to thrombin. Its activity is substantially increased when it combines with active factor five. - Factor X is the inactive form of Factor Xa

Answer 72

- converts Factor X to Xa - Intrinsic Xase is Factor IX + factor VIII, - Extrinsic Xase is Factor VII + tissue factor

Answer 73

- Vascular disorders - Platelet disorders: thrombocytopenia, defective function - defective coagulation: inherited v acquired

Answer 74

Vascular and platelet bleed cause: - bleeding into mucous membranes and skin Coagulation disorders cause: - bleeding into joints and soft tissue

Answer 75

Inherited: - Hereditary haemorrhagic telangiectasia (Oslo-Weber-Render syndrome), abnormal blood vessel formation, autosomal dominant - Ehlers-Danlos syndrome: affects connective tissue Acquired: - Scurvy - Steriods: corticosteroids in GI bleeding - Senile

Answer 76

- 150-400 x 10⁹/L - below 150 is thrmobocytopenia - symptoms are seen when plts are \<10

Answer 77

- Epistaxis - GI bleeds - menorrhagia - bruising

Answer 78

_failure to produce_ - selective megakaryocyte depression: drug toxixity or viral infection - General bone marrow failure _Increased consumption_ - immune and autoimmune - idiopathic - assoiciated ith systemic lupus erythematosus, CLL or lymphoma - infections: Helicobacter pylori, HIV, malaria drug induced = heparin

Answer 79

Immune thrombocytopenia - treat with corticosteroids - intravenous immunoglobulins: rapid rise in platelet count - sometimes a splenectomy

Answer 80

_Haemophilia A_ - sex linked chromosome - defect is in the absence of or low factor VII - largely caused by missense or frameshift mutaions or deletion in the factor VII gene _Haemophilia B_ - Christmas disease, incidence is 1/5 of Haem. A - Factor IX deficiency

Answer 81

- spontaneous bleeding into joints (haemarthrosis) and muscle - unexpected post-operative bleeding - chronic debilitating joint diseases - family history in the majority of cases

Answer 82

_Prolonged Activated Partial Thromboplastin Yome (APTT)_ - Factor VII, IX, XI, XII assay in the intrinsic pathway _Normal Prothrombin Time (PT)_ - testing factor II, V, VII, X in the intrinsic pathway - Low factor VII or IX levels: the lower the % the more severe

Answer 83

- Infusions of recombnant VIII or factor IX to 50-100% normal - if patients factor VIII is raised to 30-50% spontaneous bleeding should be controlled - 1-Diamino-8-D-arginine vasopressin (DDAVP); alternative for increasing plasma factor VIII level in milder hameophiliacs

Answer 84

- reduced level or abnormal function of von Willebrand factor (VWF) - caused by a variety of missense mutations. autosomal dominant disease _VWF_ - produced in endothelial cells and megakaryocytes - large multimeric protein that carries factor VIII in the blood, prevents its premature destruction - promotes platelet adhesion

Answer 85

- women are more badly to be affected than men at a given VWF level - mucous membrane bleeding: epistaxes, menhorrhagia - excessive blood loss from superficial cuts and abrasions - operative ad post-truamatic haemorrhage

Answer 86

- prolonged APTT - normal PT - low vWF level/ function - low factor VIII level - prolonged bleeding time - defective platlet function

Answer 87

- antifibrinolytic agent: tranexamic acid for mild bleeding - DDAVP infusion for type 1 vWD: releases VWF from endothelial cells 30 minutes after infusion - high-purity VWF for patients with very low VWF levels

Answer 88

- Vitamin K deficiency - Liver disease - Disseminated intravascular coagulation

Answer 89

- Biliary obstruction → impaired absorbiton of vitamin K. therefore decreased synthesis of clotting proteins - Decreased thrombopoeitin production from the liver contributes to thrombocytopenia - Impaired platlet function and fibrinolysis

Answer 90

This is the widespread intravascular deposition of fibrin with consumption of coagulation factors and platlets - occurs as a consquence of many disorders that release procoagulent material into the circulation or cause widespread endothelial damage or platelet agggregation - causes both bleeding and thrombosis to occur

Answer 91

- Prolonged PT, APTT, TT - Low fibrinogen - low platelts - Raised D-dimers or FDPs

Answer 92

- Heparin: used to treat- MIs, PE, DVTs - Warfarin: used to treat- PEs, DVTs, AF, prothetic valves Direct (novel) Oral anti-coagulants - Direct thrombin inhibitors: dabigatran, argatroban - Factor xa inhibitars: rivaroxaban, apixaban

Answer 93

- required for gamma-carboxylation of factors II, VII, IX, X - Inhibited by warfarin: interferes with the action of vitamin K epoxide reductase leading to functional vitamin K deficiency Deficiency can be due to: - Malabsorption of vitamin K, or inadequete in the diet, or inhibited by drugs like warfarin - Biliary obstruction (jaundice) - Haemorrhagic disease of the newborn ( give 1mg at birth )

Answer 94

- Iliac Vein - Femoral Vein - Popilteal vein - Tibial Vein

Answer 95

- more risk if a lot is above the knee as there is more risk of embolism - occur in the deep veins where blood flow is slower

Answer 96

- Hypercoagulable state: pregnancy, contraceptive pills, - Circulatory stasis: long periods of sitting/ inactivity - Epithelial injury: IV drug abuse, cancer, post operative

Answer 97

- asymptomatic - unilateral calf swelling/heat/pain/redness/hardness _Differential_ - cellulitis - Baker's cyst - muscular pain Risk factors should be considered

Answer 98

- a doppler ultrasound - shows a lack of blood flow in the leg - use a Wells score - use of a D-dimer test: indicates activation of the clotting cascade raised score indicates a DVT has a high predictive negative value

Answer 99

- Therapeutic anti-coagulation using sub-cut LMW heparin: tinzaparin or enoxaparin - Dosing is according to the patient's weight, no monitoring required - if the patient has a renal impairment (creatinine clearances less than 30ml/min) anticoagulant with i.v. unfractionated heparin is used instead. This require monitoring

Answer 100

- oral warfarin for 3-5 days - stop LMW heparin when INR (International Normalised Ratio, based on the prothrombin time) \> 2.0 for 2 days - if it's there 1st DVT (femoral or iliac)- 6 months course of warfarin - if it's there 2nd DVT/PE: lifelong warfarin - INR should be maintained between 2.0-3.0

Answer 101

- Pleuritic pain - acute dyspnoea - haemoptysis (coughing up of blood) - could cause syncope or death On examination - tachycardic - tachypnoiec - hypotensive

Answer 102

CTPA scan - CT Pulmonary angiogram

Answer 103

a V/Q scan, uses a radioisotope to get images of the lung - under perfusion, even though ventilation is very good: V/Q mismatch - underlying lung disease intermediate scans (rarely done)

Answer 104

- Sinus tachycardia: an increase in pulse rate - Atrial Fibrillation - Right Heart strain: right bundle branch block, struggle to get blood through the right lung - Classic: SI, QII, TIII pattern on the ECG (rare)

Answer 105

- usually normal - may see a small effusion - possibly linear atelectasis (shadowing)

Answer 106

- 5% mortality with treatment: even with treatment - 4% develop pulmonary hypertension: clots in the pulmonary circulation - Cause of death in 10-30% of in-patient post mortems - Up to 60% have micro-emboli at post mortem - A leading cause of ‘preventable’ death in the western world (25,000 deaths/yr in England)

Answer 107

- signs of shock, hypotension and acute SOB - Mx: thrombolysis and iv heparin - this presents with a 2-6% serious risk of bleeding

Answer 108

- LMW heparin injections – e.g. Tinzaparin - Warfarin (target INR 2.5) for 6 months - Consider underlying causes: possibly stop taking the pill - LMW heparin is better if underlying cancer - Inferior Vena Cava filters - Consider a DOAC (NOAC) as an alternative - Dabigatran p.o (direct thrombin inhibitor) - Rivaroxaban p.o (direct Xa inhibitor)

Answer 109

- occasionally in younger patients with VTE (Venous thromboembolism) - Inherited risk factors - factor V Leiden - Prothrombin gene variant _- Anti-thrombin deficiency, rare_ _- Protein C deficiency, rare_ _- Protein S deficiency, rare_ _natural anticoagulant, more prone to clotting if you are deficient in these_ - Acquired risk: anti-phospholipid syndrome - increased risk of miscarriage - the phospholipid is required as part of the formation of prothrombinase

Answer 110

* Chemotherapy – kills rapidly dividing cells: * Combination regimes * Myelo-ablative cycles of treatment * Supportive therapy: * Antibiotics, antifungals * Transfusions of blood and platelets * Allogeneic stem cell transplantation: * Allograft (full or reduced intensity) * Sibling (1-in-4 chance of being a match) * Matched unrelated donor (Anthony Nolan)

Answer 111

* Good: mutation in APML t(15;17) * Intermediate: DNMT3A, NPM1 * Poor: p53, FLT3, monosomy 7 age is the biggest risk factor for a worse prognosis, diagnosis at \>60 y/o is a worse prognosis

Answer 112

* Good: mutation in APML t(15;17) * Intermediate: DNMT3A, NPM1 * Poor: p53, FLT3, monosomy 7

Answer 113

* **CRABBI** * **_C_**alcium * Hypercalcaemia occurs as a result of increased osteoclast activity within the bones * This leads to constipation, nausea, anorexia and confusion * **_R_**enal * Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules * This causes renal damage which presents as dehydration and increasing thirst * Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis * **_A_**naemia * Bone marrow crowding suppresses erythropoiesis leading to anaemia * This causes fatigue and pallor * **_B_**leeding * bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising * **_B_**ones * Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions * This may present as pain (especially in the back) and increases the risk of fragility fractures * **_I_**nfection * a reduction in the production of normal immunoglobulins results in increased susceptibility to infection

Answer 114

* 1^st line – Tazocin (Piperacillin/Tazobactam) +/- Gentamicin * 2^nd line – Switch to Meropenem +/- Teicoplanin (for Gram +ve) * 3^rd line – Add anti-fungal e.g. Ambisome (Amphotericin) Resuscitate with IV fluids if hypotensive and may require inotropic support in ITU

Answer 115

* Caused by donor/host mismatches in major and minor HLA loci * Results in acute GVH (\<100 days) and chronic GVH (\>100 days) post-transplant * Prevented by using: * T-cell depletion of infused donor cells (graft) * Immunosuppression of recipient (ciclosporin) * Clinical manifestations: * Skin rash, sometimes severe * Diarrhoea, can be bloody * Deranged liver function, can lead to liver failure * Graft-vs-leukaemia effect is how the stem cell transplant cures leukaemia * Donor lymphocyte infusions (DLI) post-Tx can treat relapse by augmenting GVL effect

Answer 116

* NPM1 = Nucleophosmin 1 * FLT3 = Tyrosine kinase gene * DNMT3A = DNA methylation gene * initiating mutation in AML

Answer 117

* Anaemia * Infections * Disseminated Intravascular coagulation (DIC) * Ulcers * Inflitration * Bruising

Answer 118

Infiltration of malignant plasma cell in the bone marrow causing symptoms of ‘bone marrow failure’ → tiredness, infections, bruising * Plasmacytomas erode the bones causing 'lytic lesions' in bones (holes or less dense areas in imaging) * Plasma cells produce monoclonal immunoglobulin (IgG or IgA) * An M-band is detected as paraprotein serum protein electrophoresis * producing an abnormal light chain ratio in Kappa and Lambda

Answer 119

* Bloods will show anaemia (FBC) and thrombocytopenia (FBC); raised urea and creatinine (U&E) and raised calcium * Peripheral blood film: rouleaux formation * **Serum or urine protein electrophoresis:** raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins * **_Bone marrow aspiration and trephine biopsy_:** confirms the diagnosis if the number of plasma cells is significantly raised * Whole-body MRI (or CT if MRI is not suitable) is used to survey the skeleton for bone lesions

Answer 120

* Velcade, * Cyclophosphamide, * Dexamethasone _Thalidomide = immunomodulatory drug (but beware teratogenicity)_ _Bortezomib = proteasome inhibitor (or Velcade, blocks the cell’s garbage can)_ _Daratumumab = monoclonal antibody that targets CD38 on plasma cells_

Answer 121

* Hypercalcaemia * Consider myeloma * Give iv *Pamidronate* (bisphosphonate) * Give iv fliuds +/- dexamethasone * Cord compression * Consider if neurology (weak legs or cauda equina symptoms) * Request urgent MRI imaging * Surgical decompression or emergency radiotherapy * *Dexamethasone 8mg bd* * Acute renal failure caused by light chains blocking the neprons * Hydration with IV fluids * Anaemia * Blood transfusion (caution of increased viscosity of blood)

Answer 122

- they are naturally occurring complete pentameric IgM antibodies - able to fix complement and cause haemolysis

Answer 123

causes intraventricular haemolysis - shock, hypotension, tachycardia - renal failure, loin pain, haemoglobin - disseminated intravascular coagulation - death Antibodies for the red cell antigen occur naturally due to cross-reactivity with gut bacterial antigens

Answer 124

A two-part test - testing for A/B antigens - testing the serum or plasma for ABO antibodies

Answer 125

- testing to see what antibodies are in a persons blood - the serum is tested with either antigen A B or O

Answer 126

- donor red blood cells suspended with recipient serum - incubated between room temp and 37 degrees - observed to ensure no agglutination takes place

Answer 127

- These occur due to sensitisation with foreign red cell antigens, from either _previous transfusion_ or by _pregnancy_ - can cause blood transfusion reactions to take place if the patient transfused with incompatible blood in the future

Answer 128

- uses anti-immunoglobulin antibodies to agglutinate red cells - Two types, Direct and Indirect, DAT/IAT

Answer 129

Uses blood sample from the patient - tells us if the red cells are coated with antibody - positive after a transfusion reaction and in HDN - positive in autoimmune haemolytic anaemia

Answer 130

Uses recipients serum, then donor blood is added - a lab test for blood group antigens - indicates if a patient is psoitive for Rhesus and other blood groups

Answer 131

- Rh positive peopl cannot devekip antibodies - 15% of people ar Rh negative - Rh -ve people can devlope antibodies if they are transfused with Rh +ve blood or are pregnant with a rh +ve baby - this is rhesus sensitisation and the antibody generated is IgG type

Answer 132

- When a Rh(D) -ve mother is pregnant with an Rh positive fetus, - greatest cause is anti-D - she may produce antibodies (IgG) that can cross the placenta and harm the baby - this can lead to neonatal haemolytic anaemia, fetal/ neotal jaundice and kernicterus (brian damage)

Answer 133

- ABO and Rh blood group check at 12 weeks - Rh-ve women (15%) receive anti-D antibody i.m injection at 28 and 34 weeks to prevent sensitisation - baby tested at birth, if Rh +ve mother recieves further anti-D until Leihauer test (foetal cells) become negative - if already sensiised, foetus requires monitoring via trans-cranial dopplers - may require intra-uterin transfusion if there are signs of anaemia

Answer 134

- RBC - Buffy coat: whit cells, platelets - Plasma: albumin, gamma globulins, coagulation factors - wate, electrolytes, additives

Answer 135

- technique where whole blood is extracted and centrifuged into its celuular compenents and plasma - in leucapheresis, the white cells are removed - process can be used to pefrom a red cell exchange in those with sickle cell aneamia - used to isolate lymphocytes for donation; treatment of relapse following stem cell transplan - used to isolate haemopoeitic stem cells for donation

Answer 136

- Severe acute blood loss: RTA, GI blood loss, Obsttric blood loss - Elective surgery associated with significant blood loss - Medical transfusion: cnacer, chemo, renal failure

Answer 137

- Blood components: red cells, platlets, Fresh frozen plasma, cryoprecipitate (fibrinogen) - Plasma derivatives: pooled products, immunoglobulin, coagulation factors, albumin - Autologous blood ( blood to yourself)

Answer 138

- Major ABO incompatibilities - Anaphylaxis and sever allergic reaction - Minor allergic reaction - Late transfusion reactions - Fluid overload - Iron overload

Answer 139

Bacterial - Syphilis - pyogenic infections - contamination infectins (pseudomonas) Viral - Hep B, C - HIV - HTLV, CMV - Emerging- West Nile Virus - Malaria - vCJD (brain disease)

Answer 140

- Basophil - Mast cells - Platelets They act as inflammatory mediators

Answer 141

- Neutrophils - Eosinophils - Basophils

Answer 142

- not found in blood only in the tissue - releases substances that affect vascular permeability - prominent in mucosal and epithelial tissue - Express FceRI (binds IgE) - release granules containing histamine and other active agents

Answer 143

- neutrophils 50-70% - lymphocytes 20-40% - monocytes 3-10% - Eosinophil 1-3% Basophil \<1%

Answer 144

- act as part of the adaptive immune system - 5% of lymphocytes - non-specific antigens

Answer 145

- cells that are lobed nuclei and heavily granulated cytoplasm - express FceRI - circulate in the blood - recruited to sites of allergic reaction or ectoparasites - Non-phagocytic cell - can bind to allergen-specific IgE

Answer 146

- bilobed nuclei with a granulated cytoplasm: granules contain peroxidases (toxin) - motile phagocytic cells: migrate from the blood into tissues - play a role in defence against the parasitic organism: in the GI respiratory and genito-urinary tracts - Express FceRI when activated

Answer 147

- polymorphonuclear cells - multilobed nucleus - found in the blood: makeup 60% of circulating leukocytes - short lifespan: 8hr- 4days - release myeloperoxidase and ROS

Answer 148

Reactant Oxygen Species - oxygen-containing molecules that have an extra, highly reactive electron ( O₂^-) - oxygen radicals donate their electrons to other nearby molecules at random and can damage macromolecules in a random way - not a specific mechanism and can damage nearby molecules of the host

Answer 149

- kidney-shaped nucleus - there is a reservoir of monocytes in the spleen - circulate the bloodstream where they are enlarge - migrate into tissue approx. 1 day after release from the bone marrow

Answer 150

- they are tissue-specific: - 5-10x larger than monocytes: contain more organelles as well e.g lysosomes - lifespan is months to years

Answer 151

- increase in neutrophils - increase in monocytes in a chronic infection

Answer 152

- increase in lymphocytes; sometimes an increase in monocytes

Answer 153

- increase in eosinophils + activation of mast cells

Answer 154

- increase in monocytes

Answer 155

- increase in basophils - activation of mast cells - increase of eosinophils in the chronic phase

Answer 156

- Dysregulation of lipid metabolism (cholesterol) - Endothelial cell dysfunction - Inflammation: mediated by monocytes and macrophages

Answer 157

- develops within minutes - predominantly mediated by neutrophils - resolves once the stimulus is removed - lasts for hours or days

Answer 158

- predominantly mediated by mononuclear cells; macrophages,lymphocytes - tissue destruction - attempts at healing (fibrosis)

Answer 159

- Monocyte chemotactic protein-1 - aka CCL-2 - this is a chemokine, whose function is to attract leukocytes; in this case monocytes would be attracted

Answer 160

_Initial Contact_ - *P-selectin* and *E-selectin* on endothelium recognized by oligosaccharides on leukocytes _Tighter adhesion_ - intercellular adhesion molecules *(ICAMs)* on the endothelium recognised by *integrins* on leukocytes

Answer 161

- **P- selectin** binds to PSGL-1, sialyl-Lewis^x - **E-selectin** binds to sialyl-Lewis^x

Answer 162

- platelets bound to the endothelium express P-selectin and other endothelial ligands - monocytes with complementary proteins, PSGL- 1 and MAC-1 bind to the platelet - this activates the monocyte --\> inflammation of the monocyte

Answer 163

- activated macrophages also release proinflammatory cytokines: - IL-1ß, TNF-alpha, IL-6

Answer 164

Through pattern-recognition receptors such as: - Macrophage mannose receptor - Scavenger receptors - Toll-like receptors (TLRs)

Answer 165

- anionic polymers - acetylated and oxidised LDL

Answer 166

- conserved carbohydrate structures

Answer 167

- there is a range of them

Answer 168

- Mononuclear - Neutrophil - Eosinophil

Answer 169

- B cells - T cells - Large granular lymphocytes

Answer 170

- these are proteins or glycoproteins with a low molecular weight - that act as messenger molecules in the immune system - primarily secreted by WBCs - assist in regulating the development of immune effector cells - they generally act locally: paracrine signalling

Answer 171

**- ICAM-1 (CD54):** binds to LFA-1, Mac1 **- ICAM-2 (CD102):** binds toMac1 - **VCAM-1 (CD106):** binds to VLA-4 LFA-1 – Lymphocyte function-associated antigen 1 VLA-4 – Very Late Antigen-4 (Integrin alpha4beta1) VCAM-1 – Vascular cell adhesion molecule

Answer 172

- it binds monocytes and lymphocytes to _activated_ cell endothelium - expressed by endothelium over nascent fatty streaks - expressed by microvessels of the mature atheroma

Answer 173

- Vitamin K antagonist - therefore Prevents γ-carboxylation of factors II, VII, IX, X - Prolongs the extrinsic pathway (tested by measuring prothrombin time) - Monitored by the international normalised ratio (INR) - Target INR usually 2.5 for DVT/PE and AF - Target 3.5 for recurrent VTE or metal heart valves

Answer 174

- reduces the half-life of Factor VII, IX, X and II - Warfarin can take \> 3 days to reach therapeutic levels - also inhibits the natural anti-coagulants: Protein C and S - these have a shorter half-life so become prothrombotic before combing anticoagulant because the natural sources (protein C and S) are initially depleted

Answer 175

- usually loaded with low molecular weight heparin (LMWH) cover - typically: 10mg, 5mg - a fall in Protein C and S occurs within hours, can result in a temporary procoagulant state - hence, LMWH is usually continued until the INR is \> 2.0 for 2 consecutive days

Answer 176

- they are inhibitors of coagulation factor V and VIII - bothe are vitamin K dependent proteins - Protein C is activated by a thrombin-Thrombomodulin complex - activated protein C is able to destroy factor Va and VIIIa * therefore further thrombin cannot be generated: creating a **negative feedback loop** - Protein S promotes the action of protein C - activated protein C is inactivated by serpins( serum protease inactivators) e.g antithrombin ****

Answer 177

- beware of interactions with other drugs due to cytochrome P450 in the liver - enzyme inhibitors potentiate warfarin: may want to reduce the dosage - carbamazepine, azathioprine, allopurinol - erythromycin, ciprofloxacin, metronidazole, fluconazole - Enzyme inducers inhibit warfarin: may want to increase the dosage - rifampicin, amiodarone, citalopram, phenytoin - Interactions with alcohol: may have a high IRN and are at risk of bleeds

Answer 178

- teratogenic: must use LMW heparin in pregnancy - significant haemorrhage risk: leads to intracranial bleeds p to 15 a year, increased risk in elderly with a higher INR target - minor bleeding: 20% per ann. - skin necrosis - alopecia: hair loss

Answer 179

- Give vitamin K 2-10mg iv/po depending on INR level - 6-12 hours to take into effect so give other treatments first (octaplex) - The patient can become refractory to re-loading with warfarin - If life-threatening bleed, give activated prothrombin complex (Octaplex) containing factors II, VII, IX and X (25-50 units per kg), plasma-derived product - Fresh frozen plasma (FFP) can also be used

Answer 180

- Mucopolysaccharide that potentiates anti-thrombin - Irreversibly inactivates factors IIa (thrombin) and Xa - Administered parenterally Two formulations of heparin: - Unfractionated heparin given by i.v. infusion - Low molecular weight heparin given as s.c. injections _Safe in pregnancy_

Answer 181

- Not often used due to inconvenience, unless in renal failure - Given i.v. with 5000U bolus and ~1000U/hour infusion - Monitored by APTT with a target range of 1.5-2.5 x normal - Safe in renal failure - Can be _partially reversed with protamine sulphate_ - Thrombocytopenia and VTE is a rare complication resulting in heparin-induced thrombocytopenia (HIT)

Answer 182

- Very convenient due to once daily s.c. injections - Prescribed according to patient’s weight - Not usually monitored (but can use the anti-Xa assay) - Patient must have creatinine clearance of over 30ml/minute LMW heparin formulations include: - _Tinzaparin_ (Innohep) 175U/kg - Enoxaparin (Clexane) 1.5mg/kg - Dalteparin (Fragmin) Used for thromboprophylaxis for hospital in-patients: - 3,500U or 4,500U Tinzaparin - 20 or 40mg Enoxaparin

Answer 183

- alternative to warfarin - orally available, no monitoring required, has a good safety profile - **Dabigatran**: direct thrombin (IIa) inhibitor - **Rivaroxaban**: direct factor Xa inhibitor - trials show that it is as good as warfarin and LMW heparin but the anticoagulation action is irreversible

Answer 184

- used as a direct inhibitor to factor IIa (thrombin) Indications (usage) - used as a VTE (venous thromboembolism) prophylaxis - treatment for DVTs and PEs - stroke prevention in atrial fibrillation - Dosing is 110mg bd or 150mg bd - must be a creatine clearance of \> 30ml/min - _Argatroban_: direct thrombin inhibitor given iv: safe in renal failure

Answer 185

- is a direct factor Xa inhibitor Indications: - VTE prophylaxis - Used for treatment of DVTs and PEs - Stroke prevention in atrial fibrillation - Dosing is 15mg bd for 3 weeks, then 20mg od - or 15mg od if CrCl is 15-50ml/min - _Apixaban_ is alternative drug dosed bd (morning and evening), slightly better plasma levels with this drug

Answer 186

- Aspirin: cyclo-oxygenase inhibitor - Clopidogrel: ADP receptor blocker - Dipyridamole: inhibits phosphodiesterase - Prostacyclin: stimulates adenylate cyclase _Glycoprotein IIb/IIIa inhibitors:_ also used in cardiac clot prevention in patients who have had stents inserted - Abciximab – monoclonal antibody - Eptifibatide – snake venom derivative - Tirofiban – blocks platelet aggregation

Answer 187

- Thrombolytic agents are used to lyse fresh thrombi (arterial) by converting plasminogen to plasmin - e.g Tissue Plasminogen Activator (tPA, Alteplase) and Streptokinase - Administered systemically in acute MI, recent thrombotic stroke, major PE or iliofemoral thrombosis - Standardized dosage regimens have to use within 6 hours - Beware of contra-indications to thrombolysis

Answer 188

Sickle-cell anaemia is an autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS. More common in people of African descent as the heterozygous condition offers some protection against malaria. Around 10% of UK Afro-Caribbean's are carriers of HbS (i.e. heterozygous). Such people are only symptomatic if severely hypoxic Symptoms in homozygotes don't tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin

Answer 189

* haemoglobin * normal haemoglobin: HbAA * sickle cell trait: HbAS * homozygous sickle cell disease: HbSS. Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in a milder form of sickle cell disease (HbSC) * polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb * in the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle * HbAS patients sickle at p02 2.5 - 4 kPa * HbSS patients at p02 5 - 6 kPa * _sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction_

Answer 190

Haemoglobin electrophoresis

Answer 191

e.g. post-splenectomy, coeliac disease (occurs in around 30% of coeliac patients) * target cells * Howell-Jolly bodies * Pappenheimer bodies * siderotic granules * acanthocytes

Answer 192

* target cells * 'pencil' poikilocytes * if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells

Answer 193

* hypersegmented neutrophils

Answer 194

the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding One critical mediator of DIC is the release of a transmembrane glycoprotein (tissue factor =TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta

Answer 195

* sepsis * trauma * obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome) * malignancy

Answer 196

* ↓ platelets * ↓ fibrinogen * ↑ PT & APTT * ↑ fibrinogen degradation products * schistocytes due to microangiopathic haemolytic anaemia

Answer 197

Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distribution being most common in the third and seventh decades

Answer 198

* Usually present with profoundly deranged clotting - Disseminated Intravascular coagulation * increased risk of intracranial haemorrhage

Answer 199

a subtype of Acute Myeloid Leukemia they characteristically present with, represents 11% of AML cases * Hypercellular, abnormal hypergranular promyelocytes +++ * characteristically have Auer rods * Immunophenotyping: CD34, HLA-DR -ve / MPO, CD13, CD33 +ve * Rapid interphase FISH analysis: _PML-RARA rearrangement t(15;17)_ * PCR: PML-RARA confirmed by real time PCR

Answer 200

* raising WCC * the rapid differentiation of promyelocytes results in the release of cytokines resulting in target organ damage e.g lungs causing ARDS * Dyspnoea, fever, weight gain oedema * Txt: by stopping ATRA and dexamethasone

Answer 201

* Induction treatment with **ATRA - All-trans retinoic acid (Vitamin A)** * binds to the receptor and induces differentiation of the promyelocytes which allows the cells to progress along normal myeloid differentiation → Risk of *Differentiation syndrome,* occurs in 15% of patients. All the promyelocytes simultaneously differentiate and then enter into circulation and causing infiltration of the tissues e.g the Lungs resulting in ARDS * 2nd cycle consolidation treatment with more ATRA or **Arsenic trioxide**

Answer 202

* Neutropenia * Marked thrombocytopenia * Primitive myeloid blast cells * Auer rods seen

Answer 203

* taken from the iliac crest with patient curld up * Look at the bone marrow aspirate, BM trephine (keeps bone marrow intact) * Flow cytometry * Molecular analysis - mutations in known AML genes: * DNMT3A (DNA methyltransferase gene) = poor risk * CEBPA (myeloid transcription factor) = good risk * GATA2 (myeloid transcription factor) = neutral * FLT3 and NPM1

Answer 204

* Insertion of PICC line * Patient commenced on standard “DA 3+10” chemotherapy regime: (causes pancytopenia) * Daunorubicin (anthracycline) – infusions days 1, 3, 5 * Cytarabine (nucleoside analogue) – bd infusions days 1-10 * Daily platelet support to maintain above 50 x 10⁹/L * Red cell transfusions to maintain above 90g/L * Broad-spectrum antibiotics started for neutropenic fever, high CRP: * Tazocin * Teicoplanin and also give antifungal treatment

Answer 205

* High early mortality due to haemorrhrage * Initial management is to prevent bleeding * Overall prognosis today is 80-90% survival at 10 years * usually presents in young people which helps with prognosis

Answer 206

Binet Staging: this is classified by the number of lymphoid tissues involved (e,g spleen, lymph nodes of the neck, groin and under arms), and the presence of Anemia and Thrombocytopenia * **stage A** (monitored) * fewer than three areas of enlarged lymphoid tissue * no anaemia * no thrombocytopenia * \* lymphadenopathy in the neck, axillary, inguinal as well as the splenic involvement, are each considered as "one group," whether unilateral (one-sided) or bilateral (on both sides) * **stage B** * three or more areas of enlarged lymphoid tissue * no anaemia * no thrombocytopenia * **stage C** * patients have anaemia and/or thrombocytopenia regardless of lymphadenopathy

Answer 207

Most common leukaemia. It is slowly progressing that begins in the lymphocytes of bone marrow and extends into the blood. This causes painless enlarged lymph nodes, pain in upper left side of abdomen, night sweats, weight loss, and fever

Answer 208

* **Ibrutinib:** Bruton tyrosine kinase inhibitor * Haemorrhagic colitis * Hypertension * Arrhythmias * **Rituximab**: targets B lymphocytes via binding to CD20 * **Venetoclax**: Bcl-2 (B-cell lymphoma - 2) inhibitor * Tumour lysis: prevented by weekly step-wise escalation of venetoclax daily dose over 5 weeks (when the WCC normalises) * twice weekly tumour lysis syndrome blood monitoring with each increment → all medications are targeting B cells therefore likely to develop immune paresis (low Ig's) increasing risk of opportunistic infections

Answer 209

likely to progress to non-Hodgkins Lymphoma

Answer 210

* a complication of Venetoclax (Bcl-2 inhibitor) * it is a result of mass cell apoptosis caused by the drug, releasing the cell contents causing * Hyperkalaemia, hyperphosphataemia, hypocalcemia and raised creating presenting in renal failure * can cause arrhythmias due to high potassium * Treated with * Hydration, IV * *_Rasburicase*_ to break down urate then _*Allopurinol_*, to prevent urate nephropathy

Answer 211

* Type of lymphoproliferative disorder * Lymphocyte count \> 5x10⁹/L * Splenomegaly + lymphadenopathy * CLL work-up: * Diagnosis by morphology and immunophenotyping * Staging by Binet system (A,B,C) * Management is determined by p53 mutation or deletion (del17p) * these patients have a more targeted therapies required more targeted therapies from the onset * IgVH mutation stats can also help to determine prognosis

Answer 212

* Treatment is indicated for marrow failure (cytopenias): * If p53 wild-type: * First line treatment with chemo-immunotherapy regime FCR: * Fludarabine, cyclophosphamide, rituximab (anti-CD20 monoclonal Ab) * If less fit then for Bendamustine/Rituximab or Chlorambucil/Obinutuzumab treatment * If p53 mutated or deleted, or relapsed CLL disease then for targeted therapy: * Ibrutinib (oral BTK inhibitor = Bruton’s tyrosine kinase) * Venetoclax (oral BCL2 inhibitor = anti-apoptotic protein) * Idelalisib (oral PI3K inhibitor = B cell receptor signalling protein) * If CLL is complicated by AIHA or ITP, then treat with steroids (prednisolone)

Answer 213

* Triggers apoptosis of CLL cells )sometimes causing tumour lysis syndrome) * Results in eradication of detectable MRD in a proportion of patients * Venetoclax approved in 2016 for patients with CLL: * with 17p deletion or *TP53* mutation or relapse post-first line chemo-immunotherapy

Answer 214

* Anaemia * low platelets * High white cells - mainly neutrophils * High B12 levels and LDH levels * Blood film * Leucoerythroblastic blood film (red cells with a nucleus) * bone marrow is under stress and is releasing premature red cells and myeloid cells * Myelocytes * Teardrop red cells

Answer 215

* Hypercellular on bone marrow aspirate * Excess myeloid cells with left shift * Reticulin fibrosis grade 3 on trephine * Abnormal megakaryocytes * Mild increase in CD34+ve blasts * +ve JAK2 V617F mutation

Answer 216

* **Hydroxycarbamide** 500mg daily initially - to lower white cells * causes reduction in splenomegaly * **Allopurinol** 300mg daily for gout and urate nephropathy prevention * **Ruxolitinib** (JAK2 inhibitor)

Answer 217

* Splenomegaly causing abdominal pain * can cause pain radiating to the shoulder due to irritation of the diaphragm C3,4,5 * _Fatigue_ * Nightsweats * Itchiness (pruritis) * Bone pain * Weight loss

Answer 218

* Essential thrombocytopenia → polycythemia vera * both can form Myelofibrosis * Myelforbisos → Acute Myeloid Leukaemia

Answer 219

* Confirm diagnosis by JAK2 mutation analysis * If -ve, rule out reactive thrombocytosis * Raised inflammatory markers? * Malignancy, infection, bleeding etc? * Bone marrow biopsy – increased megakaryocytes? * If age \< 60 and plts \< 1500 and no hx of VTE then Aspirin only * If \> 60 or plts \> 1500 or previous VTE or other significant risk factors, then add Hydoxycarbamide to maintain platelets in normal range

Haematology Flashcards

(253 cards)