Haematology Flashcards

Question

Define: poikilocytosis

Answer 1

RBCs show more variation in SHAPE than is normal

Answer 2

RBCs are SMALLER than normal

Answer 3

RBCs are LARGER than normal

Answer 4

RBC that is smaller than normal

Answer 5

RBC that is larger than normal

Answer 6

Round macrocytes Oval macrocytes Polychromatic macrocytes

Answer 7

When a patient is deficient in vitamin K or folic acid

Answer 8

Cell initially polychromatic if released prematurely from bone marrow before maturation Ribosomal RNA gives unusual colour

Answer 9

RBCs that are smaller than normal or an anaemia with small red cells

Answer 10

RBCs that are bigger than normal or an anaemia with large red cells

Answer 11

RBCs that are normal or an anaemia with normal sized red cells

Answer 12

A third Due to disk shape of the red cell Centre has less haemoglobin-> therefore paler

Answer 13

The cells have a larger area of central pallor than normal | Results from lower haemoglobin content and conc and a flatter cell

Answer 14

The cells lack central pallor | Can occur because they are thicker than normal or have an abnormal shape

Answer 15

Spherocytes | Irregularly contracted cels

Answer 16

Uniform density, very round Reduced diamete Lack central pallor Gradual change

Answer 17

Dense but outline is irregular | Lost their central pallor

Answer 18

Loss of cell membrane without loss of an equivalent amount of cytoplasm Cell is forced to round up Can be hereditary spherocytosis

Answer 19

Oxidant damage to the cell membrane and to haemoglobin | Some people may be deficient in enzyme so can't protect from oxidant damage

Answer 20

Increased blue tinge to the cytoplasm of a RBC | Indicates RBC is young

Answer 21

Polychromasia OR Reticulocyte stain (more reliable)

Answer 22

Exposes living red cells to new methylene blue, which precipitates as a network or ‘reticulum’

Answer 23

``` Spherocytes Irregularly contracted cells Sickle cells Target cells Elliptocytes Fragment ```

Answer 24

Schistocytes (fragments produced by splitting of cell)

Answer 25

Cells with an accumulation of haemoglobin in the centre of the area of central pallor

Answer 26

Obstructive jaundice Liver disease Haemoglobinopathies Hyposplenism

Answer 27

Elliptical in shape | Occurring in hereditary elliptocytosis and in iron deficiency

Answer 28

Sickle or crescent shaped | Result from the polymerization of haemoglobin S when it's present in a high concentration

Answer 29

When a red cell has fragmented into schistocytes | Can form due to abnormal stress on a RBC or the cell is intrinsically normal

Answer 30

Stack of red cells resembling a pile of coins | Caused by alterations in plasma proteins which stop RBCs repelling each other as they normally do

Answer 31

Agglutinates are irregular clumps rather than tidy stacks

Answer 32

Result from antibody on the surface of the cells

Answer 33

Inclusions | Nuclear remnant in a red cell

Answer 34

Lack of splenic function

Answer 35

Too many WBCs

Answer 36

Too few WBCs

Answer 37

Too many neutrophils

Answer 38

Too many neutrophils

Answer 39

Too many lymphocytes

Answer 40

Too many eosinophils

Answer 41

Too many platelets

Answer 42

Too few platelets

Answer 43

Too many RBCs

Answer 44

Too many reticulocytes

Answer 45

Too few lymphocytes NB. Not called lymphocytopenia

Answer 46

Infectious mononucleosis (glandular fever) Sometimes called atypical mononuclear cells

Answer 47

Toxic granulation is heavy granulation of neutrophils It results from infection, inflammation and tissue necrosis (but is also a normal feature of pregnancy)

Answer 48

Neutrophil has increased in average number of lobes or segments (around 5 is called segmented)

Answer 49

Lack of vitamin B12 or folic acid

Answer 50

``` Age Gender Ethnic origin Physiological status Altitude Nutritional status Cigarette smoking, alcohol intake ```

Answer 51

Hb rises with altitude Lower amount of oxygen available Greater erythropoietin drive to kidney

Answer 52

Carefully defined reference population Samples collected from healthy volunteers with defined characteristics Analysed using same instrument and techniques that will be used for patient

Answer 53

Gaussian distribution can be analysed by determining mean and standard deviation Mean +/- 2SD as 95% range

Answer 54

True (a result within the 95% range determined from apparently healthy people may still be bad for your health)

Answer 55

g/L | Used to be g/dL

Answer 56

White blood cell count in a given volume of blood (× 109/l)

Answer 57

Red blood cell count in a given volume of blood (× 1012/l)

Answer 58

Haemoglobin concentration (g/l)

Answer 59

Packed cell volume (l/l)

Answer 60

Haematocrit (l/l)

Answer 61

Mean cell volume (fl)

Answer 62

Mean cell haemoglobin (pg)

Answer 63

Mean cell haemoglobin concentration (g/l)

Answer 64

the number of platelets in a given volume of blood (× 109/l)

Answer 65

Counted in large automated instruments, by enumerating electronic impulses generated when cells flow between a light source and a sensor or when cells flow through an electrical field Initially counted visually, using a microscope and a diluted sample of blood

Answer 66

Now measured by an automated instrument Initially measured in a spectrometer (convert Hb to stable form with cyanide and measure light absorption at a specific wave length)

Answer 67

Centrifuging a blood sample

Answer 68

Determined indirectly by light scattering or by interruption of an electrical field Can be calculated bydividing the total volume of red cells in a sample by the number of red cells in a sample, i.e. by dividing the PCV by the RBC

Answer 69

Amount of haemoglobin in a given volume of blood divided by the number of RBCs in the same volume Hb/RBC

Answer 70

Amount of Hb in a given volume of blood / proportion of sample represented by the RBCs Hb/PCV or Hb/hct Electronically measured with light scattering-> plots

Answer 71

The MCH is the absolute amount of haemoglobin in an individual red cell The MCHC is the concentration of haemoglobin in a red cell (measures the average amount of Hb in an individual RBC) - Related to shape of the cell

Answer 72

The MCH tends to parallel the MCV

Answer 73

Is there leucocytosis or leucopenia? Why? Which cell line is abnormal? Are there any clues in the clinical history? Is there anaemia? Are there any clues in the blood count? Are the cells large or small? Are there any clues in the clinical history? Is there thrombocytosis or thrombocytopenia? If so, are there any clues in the blood count? Are there any clues in the clinical history? Interpret - WBC and differential - Hb - MCV - Platelet count Then look at the other measurements

Answer 74

See the cause e.g. of a patient's anaemia

Answer 75

Too many red cells in the circulation

Answer 76

Hb, RBC and PCV/Hct are all increased compared with normal subjects of the same age and gender

Answer 77

Start with a clinical history and physical examination (splenomegaly, abdominal mass or cyanosis could be relevant) Next compare with an appropriate normal range

Answer 78

Neonate= highest Lower in children than adults Lower in women than in men

Answer 79

High Hb, RBC and PCV/Hct Pseudopolycythaemia or apparent polycythaemia

Answer 80

When the abnormalities result from an increase in the number of circulating red cells

Answer 81

Medical negligence Blood doping (illicit erythropoietin) From the action of erythropoietin that is appropriately elevated e.g. as a result of hypoxia Tumour secreting erythropoietin (often renal tumour) Abnormal function of the bone marrow (polycythaemia vera which is a myeloproliferative neoplasm)

Answer 82

Intrinsic bone marrow disorder A myeloproliferative neoplasm - > Inappropriately increased erythropoiesis - > Thick blood (hyperviscosity) - > Can cause vascular obstruction

Answer 83

Blood can be removed to thin the blood | Venosection then drug

Answer 84

Reduce bone marrow production of RBCs with drug

Answer 85

Probably due to hypoxia

Answer 86

Carcinoma of the kidney

Answer 87

Pointer to polycythaemia vera

Answer 88

Reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender Hb is reduced Usually RBC and the PVC/Hct are also reduced

Answer 89

Due to reduction of the absolute amount of haemoglobin in the blood stream OR (OCCASIONALY) results from increased volume of plasma rather than a decrease in the amount of haemoglobin

Answer 90

It results from an increase in plasma volume Because excess fluid in the circulation is excreted

Answer 91

Reduced production of RBCs/Hb in the bone marrow Loss of blood from the body Reduced survival of red cells in the circulation Pooling of red cells in a very large spleen

Answer 92

MECH= might be reduced synthesis of haemoglobin in the bone marrow CAUSE= could be either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin

Answer 93

Microcytic (usually also hypochromic) Normocytic (usually also normochromic) Macrocytic (usually also normochromic)

Answer 94

Defect in haem synthesis | Defect in globin synthesis (thalassaemia)

Answer 95

Iron deficiency | Anaemia of chronic disease

Answer 96

Defect in alpha chain synthesis (a thalassaemia) | Defect in beta chain synthesis (B thalassaemia)

Answer 97

Usually from abnormal haemopoiesis so the RBC precursors continue to synthesize haemoglobin and other cellular proteins but they fail to divide normally This means red cells end up larger than normal

Answer 98

Delay in maturation of the nucleus while the cytoplasm continues to mature and cell continues to grow Causes macrocytic anaemia

Answer 99

Abnormal bone marrow erythroblast (morphological change in RBC precursors within BM) Larger than normal and shows nucleo-cytoplasmic dissociation (asynchronous maturation)

Answer 100

Young red cells are about 20% larger than mature red cells | So increased proportion of reticulocytes-> increased average cells size (MCV increased)

Answer 101

Lack of vitamin B12 or folic acid Drug use of drugs interfering with DNA synthesis Liver disease and ethanol toxicity Recent major blood loss with adequate iron stores Haemolytic anaemia (reticulocytes increased)

Answer 102

Recent blood loss Failure of production of red cells Pooling of red cells in the spleen

Answer 103

Peptic ulcer, oesophageal varices, trauma Failure of production of RBCs Hypersplenism e.g. portal cirrhosis

Answer 104

Early stages of iron deficiency or anaemia of chronic disease Renal failure Bone marrow failure or suppression Bone marrow infiltraion

Answer 105

Anaemia resulting from shortened survival of red cells in circulation

Answer 106

Intrinsic abnormality of the red cells Extrinsic factors acting on normal red cells (can also have extrinsic factors interacting with RBCs that have an intrinsic abnormality)

Answer 107

Intrinsic Extrinsic Inherited= form abnormalities in the cell membrane, Hb or enzymes in the RBC Acquired= from extrinsic factors e.g. micro-organisms, chemicals or drugs that damage the red cell Intravascular= very acute damage to the red cell Extravascular= defective red cells are removed by the spleen (Can be partly intravascular and partly extravascular)

Answer 108

Abnormal red cell membrane e.g. spherocytosis Abnormal Hb e.g. SCA Defect in glycolytic pathway e.g. pyruvate kinase deficiency Defect in enzymes of pentose shunt e.g. G6PD deficiency DON'T NEED TO KNOW SPECIFIC EGS OF CAUSES

Answer 109

Damage to red cell membrane e.g. AIHA or snake bite Damage to whole red cell e.g. MAHA Oxidant exposure, damage to red cell membrane and Hb e.g. dapsone or primaquine DON'T NEED TO KNOW SPECIFIC EGS OF CAUSES

Answer 110

Square ends= polymerisation form 1 HbS HbS from one parent HbA from the other

Answer 111

Haemolytic anaemia

Answer 112

Patient develops immune response against its own RBCs

Answer 113

Membrane (hereditary spherocytosis) Haemoglobin (SCA) Glycolytic pathway (pyruvate kinase deficiency) Pentose shunt (glucose-6-phosphate dehydrogenase deficiency)

Answer 114

Membrane- immune (autoimmune haemolytic anaemia) Whole red cell- mechanical (microangiopathic haemolytic anaemia) Whole red cell- oxidant (drugs and chemicals) Whole red cell- microbiological (malaria)

Answer 115

Inherited, intrinsic defect of red cell membrane After entering circulation, cells lose membrane in the spleen and become spherocytotic Red cells become less flexible and are removed prematurely by the spleen- extravascular haemolysis Bone marrow responds-> increased RBC output -> polychromasia and reticulocytosis Haemolysis-> increased bilirubin production, jaundice and gallstones

Answer 116

Causes haemolytic anemia or chronic compensated haemolysis

Answer 117

More Osmotic fragility test

Answer 118

Splenectomy (effective but has risks so only in severe cases) Good diet important (prevent secondary folic acid deficiency doesn't occur) Nowadays in Western countries- food supplement with folic acid or take 1 tablet daily

Answer 119

Important enzyme in the pentose phosphate shunt | Protects the RBC from oxidant damage

Answer 120

In the blood stream e.g. during infection | Or may be exogenous

Answer 121

Foodstuffs e.g. broad beans Chemicals e.g. naphthalene Drugs e.g. dapsone, primaquine

Answer 122

Hemizygous males (can be homozygous females) Because gene for G6PD is usually on the X chromosome

Answer 123

Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant

Answer 124

Appearance of considerable numbers of irregularly contracted cells Haemoglobin denatured and formed round inclusions known as Heinz bodies (detected by specific test)

Answer 125

Round inclusions formed when haemoglobin is denatured | Removed by the spleen, leave a defect in the cell

Answer 126

Blood transfusion | Then prevention

Answer 127

Production of autoantibodies directed at red cell antigens Immunoglobulin bound to RBC membrane is recognised by splenic macrophages which remove parts of RBC membrane-> spherocytosis Combo of cell rigidity (from spherocytes) and recognition of antibody/complement-> removal of cells from circulatoin by the spleen

Answer 128

Immunoglobulin bound to RBC membrane is recognised by splenic macrophages which remove parts of RBC membrane-> spherocytosis

Answer 129

Finding spherocytes and an increased reticulocyte count Detecting immunoglobulin on the red cell surface Detecting antibodies to red cell antigens or other autoantibodies in the plasma

Answer 130

Use of corticosteroids and other immunosuppressive agents | Splenectomy for severe cases

Answer 131

Iron deficiency

Answer 132

Renal carcinoma

Answer 133

Iron is an essential element due to its ability to gain and lose electrons easily and also its ability to bind oxygen

Answer 134

``` Ribonucleotide reductase Cyclo-oxygenase Succinate dehydrogenase Cytochrome a, b, c Cytochrome P450 Catalase Haemoglobin (MOST IRON) Myoglobin ```

Answer 135

Holds onto oxygen | Consequences of iron deficiency seen in blood

Answer 136

Haem (and iron) + globin Each haem group is associated with a single globin chain Haem sits in a pocket formed by the globin chain

Answer 137

Consists of a ring of carbon, hydrogen and nitrogen atoms In its centre is an iron atom in the ferrous (Fe2+) state Heme combines reversibly with oxygen

Answer 138

``` 20mg iron/day Fortunately iron is recycled Women need more (lose because of menstruation) Men need 1mg/day Women need 2mg/day ```

Answer 139

Desquamated cells of skin and gut | Bleeding =menstruation or pathological

Answer 140

Human diet provides 12-15mg iron/day BUT most eaten iron is not absorbed Iron occurs in most natural foods especially: - Meat and fish(haem iron) - Vegetables - Whole grain cereal - Chocolate

Answer 141

Can’t absorb ferric iron Fe3+ (Can only absorb ferrous iron Fe2+) Worsened by tea Improved by orange juice

Answer 142

There are no regulated mechanisms for iron excretion

Answer 143

Diet= increase in haem iron, ferrous iron Intestine= acid (duodenum), ligand (meat) Systemic= iron deficiency (anaemia/hypoxia and pregnancy)

Answer 144

High iron - high hepcidin - low ferroportin- low absorption When hepcidin binds to and induces degradation of ferroportin-> iron is stuck in enterocytes-> shed-> iron is effectively lost from body

Answer 145

Only known iron exporter in mammals | Protein controlled by peptide hormone (hepcidin)

Answer 146

Hepcidin is a peptide hormone (25 AA hormone, highly conserved in all vertebrates) Binds to and induces degradation of ferroportin-> iron is stuck in enterocytes-> shed-> iron is effectively lost from body Reduces iron entering blood from duodenum, macrophages and hepatocytes

Answer 147

Enterocytes of the duodenum Macrophages of the spleen which extract iron from old or damaged cells Hepatocytes

Answer 148

Ion in diet-> IC iron to ferritin-> iron in plasma (transferrin)

Answer 149

Transferrin is the major EC iron binding protein (very abundant) Holds onto iron in the circulation Forms stable complexes with iron and more than 40 other metal ions It cannot transport iron inside the cells where it is needed

Answer 150

Can't transport iron into cells Transferrin-iron interacts with the transferrin receptor and is internalised As the pH drops iron is released and transferrin receptors are recycled

Answer 151

Toxic Insoluble Need iron binding proteins and transport systems

Answer 152

Hormone secreted by the kidneys that increases the rate of production of RBCs in response to falling levels of oxygen in the tissues

Answer 153

Anaemia-> tissue hypoxia-> increase in erythropoietin-> red cell precursors (survive, grow, differentiate)

Answer 154

Anaemia in patients who are unwell | No obvious cause (no bleeding, marrow infiltration or iron/B12 or folate deficiency)

Answer 155

C-reactive protein Erythrocyte sedimentation rate Acute phase response- increases in ferritin, FVIII, fibrinogen, immunoglobulins

Answer 156

Chronic infections e.g. TB/HIV Chronic inflammation e.g. RhA/SLE Malignancy Miscellaneous e.g. cardiac failure

Answer 157

Cytokines prevent the usual flow of iron from duodenum to red cells-> BLOCK IN IRON UTILISATION ``` Cytokines e.g. TNFa and interleukins: Stop erythropoietin increasing Stop iron flowing out of cells Increase production of ferritin Increase death of red cells ``` THEREFORE Make less RBCs More RBCs die Less availability of iron (stuck in cells/ferritin)

Answer 158

Bleeding MAIN CAUSE e.g. menstrual/GI Increased use e.g. growth/pregnancy Dietary deficiency e.g. vegetarian Malabsorption e.g. coeliac

Answer 159

Male Women over 40 Post menopausal women Women with scanty menstrual loss

Answer 160

Upper GI endoscopy - oesophagus, stomach, duodenum Take duodenal biopsy Colonoscopy IF FIND NOTHING Small bowel meal and follow through

Answer 161

Blood tests GI investigations Check urinary blood loss (renal cancer) Antibodies for coeliac disease

Answer 162

``` MCV (mean cell volume) Serum iron Ferritin Transferrin (= total iron binding capacity, TIBC) Transferrin saturation ```

Answer 163

Serum iron | Haemoglobin electrophoresis- confirms an additional type of haemoglobin is present

Answer 164

LOW in iron deficiency HIGH in chronic disease BUT ferritin can be normal despite iron deficiency (e.g. RhA plus bleeding ulcer)

Answer 165

Raised CRP | Raised ESR

Answer 166

TRANSFERRIN Iron deficiency: transferrin goes up Chronic disease: Normal or even low TRANSFERRIN SATURATION Iron deficiency: Low saturation Chronic disease: Normal

Answer 167

Suggests iron deficiency | He needs to have upper and lower GI endoscopies to look for a source of bleeding

Answer 168

``` Hb= LOW MCV= LOW Serum iron= LOW Ferritin= LOW Transferrin= HIGH Transferrin saturation= LOW ```

Answer 169

``` Hb= LOW MCV= LOW or N Serum iron= LOW Ferritin= HIGH or N Transferrin= NORMAL/LOW Transferrin saturation= NORMAL ```

Answer 170

``` Hb= LOW MCV= LOW Serum iron= NORMAL Ferritin= NORMAL Transferrin= NORMAL Transferrin saturation= NORMAL ```

Answer 171

``` Hb= LOW MCV= LOW Serum iron= LOW Ferritin= NORMAL Transferrin= LOW Transferrin saturation= NORMAL/LOW? ```

Answer 172

BLOOD FILM Small, pale, strange shapes (including pencil cells) BONE MARROW Stain for iron

Answer 173

DNA synthesis | Integrity of the nervous system

Answer 174

Severe anaemia | Can be fatal

Answer 175

DNA synthesis | Homocystine metabolism

Answer 176

Needed for production of deoxythmidine from deoxyuridine (important for DNA synthesis)

Answer 177

All rapidly dividing cells are affected | Including bone marrow, epithelial surfaces of mouth and gut, gonads, embryos

Answer 178

``` Anaemia (macrocytic and megaloblastic)-> weak, tired, short of breath Jaundice Glossitis and angular cheilosis Weight loss, change of bowel habit Sterility ```

Answer 179

Macrocytic and megaloblastic

Answer 180

``` Vitamin b12/folate deficiency Liver disease or alcohol Hypothyroid Drugs e.g. azathioprine Haematological disorders (e.g. myelodysplasia, aplastic anemia, reticulocytosis) ```

Answer 181

Erythroblast Normoblast: early/intermediate/late Reticulocyte Circulation RBC

Answer 182

Bone marrow

Answer 183

Anisocytosis Large red cells Hypersegmented neutrophils Giant metamyelocytes

Answer 184

False (can cause macrocytosis but not megaloblastic change in BM)

Answer 185

False (macrocytic)

Answer 186

``` Check folate Thyroid function test Liver function test B12 Reticulocyte count Blood film ```

Answer 187

Fresh leafy veg | Destroyed by overcooking/canning/processing

Answer 188

Ignorance Poverty Apathy N.B. elderly alcoholics

Answer 189

PHYSIOLOGICAL Pregnancy Adolescence Premature babies PATHOLOGICAL Malignancy Erythoderma Haemolytic anaemias

Answer 190

FBC and blood film | Folate levels in blood

Answer 191

History- diet, alcohol, illness | Exam- skin disease/alcoholic liver disease

Answer 192

Megaloblastic, macrocytic anaemia Neural tube defects in developing foetus Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

Answer 193

Prevents neural tube defects e.g. spina bifida, anencephaly

Answer 194

0.4mg prior to conception and for first 12 weeks

Answer 195

VERY HIGH Atherosclerosis Premature vascular disease MILDLY ELEVATED CV disease Probably arterial thrombosis Possibly venous thrombosis

Answer 196

Bilateral peripheral neuropathy Subacute combined degeneration of the cord (posterior and pyramidal tracts of SC) Optic atrophy Dementia

Answer 197

Enlarged tongue Premature grey hair ``` HISTORY Paraesthesia Muscle weakness Difficulty walking Visual impairment Pyschiatric disturbance Neurological problems ``` EXAM Absent reflexes and upgoing plantar responses

Answer 198

Poor absorption Reduced dietary intake (vegans at risk, stores last 3-4 years) Infections/infestations (e.g. abnormal bacterial flora, tropical sprue, fish tapeworm)

Answer 199

In small intestine 2 methods 1. Slow and innefficient 1% in duodenum 2. B12 combines with intrinsic factor (made by stomach parietal cells) and then B12-IF binds to ileal receptors Then B12 is stored (saturated stores-> excess B12 excreted in urine)

Answer 200

Intact stomach Intrinsic factor Functioning small intestine

Answer 201

Reduced IF due to: - Post gastrectomy - Gastric atrophy - Antibodies to IF or parietal cells B12 needs to combine with IF and then b12-IF binds to ileal receptors-> B12 absorptionn

Answer 202

Autoimmune condition associated with severe lack of intrinsic factor Normally around 60y old with family hx Males have decreased life expectancy

Answer 203

Intrinsic factor antibodies - Occasionally found in other conditions Parietal cell antibodies - 90% adults with PA - 16% normal females over age of 60 - Increased in relative of patients with PA

Answer 204

Crohns Coeliac disease Surgical resection

Answer 205

H pylori Giardia Fish tapeworm Bacterial overgrowth

Answer 206

Metformin Proton pump inhibitors e.g. omeprazole Oral contraceptive pill

Answer 207

``` Antibodies to parietal cells and intrinsic factor Antibodies for coeliac disease Breath test for bacterial overgrowth Stool for H Pylori Test for Giardia ```

Answer 208

Schilling test

Answer 209

Measure methylmalonyl acid Measure homocysteine Look for anti-intrinsic factor antibodies Treat as B12 deficiency until you get all of the results back

Answer 210

Injections of B12…. 1000ug 3x/week for 2 weeks Thereafter every 3 months IF NEUROLOGICAL INVOLVMENT B12 injections alternate days until no further improvement – up to 3 weeks Thereafter every 2 months

Answer 211

2. Folate, B12, thyroid function, liver function

Answer 212

PRIMARY HAEMOSTASIS Vessel constriction Formation of an unstable platelet plug (platelet adhesion and aggregation) SECONDARY HAEMOSTASIS Stabilisation of plug with fibrin (blood coagulation) Dissolution of clot and vessel repair (fibrinolysis)

Answer 213

First stage of haemostatic plug formation Mainly important in small blood vessels Local contractile response to injury, precise mechanisms uncertain

Answer 214

PROLIFERATION (in bone marrow) Stem cell precursors (2n) undergo nuclear replication to form megakaryocytes and become multinucleate 2-4-8-16 MATURATION WITH GRANULATION (in bone marrow) CIRCULATION Each megakaryocyte produces 4000 platelets

Answer 215

``` Microtubules and actomyosin Glycogen Phospholipid membrane Open cannalicular system Mitochondrion Receptor for thrombin Alpha granules Dense granules Surface glycoprotein ``` NO NUCLEUS

Answer 216

GFs Fibrinogen Factor V vWF

Answer 217

ADP ATP Serotonin Ca2+

Answer 218

GpIa GpIb GpIIb/IIIa

Answer 219

Recruitment of platelets from flowing blood to site of injury

Answer 220

Between adhesion and aggregation

Answer 221

Vascular injury-> damaged endothelium which exposes collagen in the sub-endothelial matrix Sub-endothelial collagen binds to VWF and recruits them to endothelial surface Rheological shear forces of flowing blood through vessel then unravels the VWF on the endothelial surface Unravelled VWF has exposed binding site (Gp1b) therefore platelets bind Platelets also bind to Gp1a under low shear forces Binding recruits the platelets to site of vessel damage

Answer 222

Glycoprotein

Answer 223

VWF are in a globular conformation so binding sites are hidden from platelets

Answer 224

Unravelled VWF has exposed binding site (Gp1b) therefore platelets bind Platelets can also bind directly to the exposed collagen via Gp1a but this is only under low shear forces

Answer 225

Conversion from passive to interactive functional cell Cell spreads and flattens-> changed membrane composition Present new proteins on their surface (GpIIb/GpIIIa) Platelets bound to collagen on VWF release ADP and thromboxane which activate platelets Collagen and thrombin also activate platelets

Answer 226

ADP Thromboxane Collagen Thrombin

Answer 227

Activated platelets bind more tightly to the collagen and VWF via GpIIb/IIIa GpIIb/IIIa also binds fibrinogen, which develops the platelet plug

Answer 228

Helps slow bleeding and provides a surface for coagulation

Answer 229

Blood coagulation Stops blood loss Complex biochemical process

Answer 230

Circulate as inactive precursors (zymogens ) Then activated by specific proteolysis (to form either as serine protease zymogens or cofactors)

Answer 231

Liver – most plasma haemostatic proteins Endothelial cells – VWF. TM, TFPI Megakaryocytes – VWF, FV

Answer 232

Endothelial cells-> prostacyclin Platelets-> thromboxane A2

Answer 233

``` Membrane phospholipid -> PHOSPHOLIPASE-> Arachidonic acid -> COX-1 (aspirin)-> Endoperoxides (PGG2, PGH2) -> PROSTACYCLIN SYNTHETASE-> Prostacyclin (pGI2) ```

Answer 234

Prostacyclin is a potent inhibitor of platelet function

Answer 235

Potent inducers of platelet aggregation when secreted

Answer 236

``` Membrane phospholipid -> PHOSPHOLIPASE-> Arachidonic acid -> COX-1 (aspirin)-> Endoperoxides (PGG2, PGH2) -> THROMBOXANE SYNTHETASE-> Thromboxane A2 ```

Answer 237

Antiplatelet agents ADP receptor antagonists= clopidogrel, prasugrel COX1 antagonist= aspirin GpIIb/IIIa antagonist= abciximab, tirofiban, eptifibatide Combo used during interventions (angioplasty, stents)

Answer 238

Platelet count

Answer 239

``` Normal= 150-400 x 109/L No spontaneous bleeding but bleeding with trauma= 40-100 x 109/L Spontaneous bleeding common= <40x 109/L Severe spontaneous bleeding (e.g. treatment of leukaemias)= <10 109/L ``` Auto-ITP= around 40x 109/L

Answer 240

Purpura Multiple bruises Ecchymoses

Answer 241

Bleeding time | Platelet aggregation

Answer 242

Standardised incision and cuff with 40mm pressure Bleeding time normally 3-8 minutes Used to check platelet-vessel wall interaction, when platelet count is normal, e.g. renal disease

Answer 243

Measures functional defect of platelets | E.g. vWF disease, inherited platelet defects

Answer 244

Liver= most coagulation proteins Endothelial cells= vWF Megakaryocytes (platelets)+ Factor V, vWF

Answer 245

Intrinsic pathway Extrinsic pathway Common pathway

Answer 246

Initiated when FXII is activated (not biologically as important) FVIIIa is the only cofactor, all other activated clotting factors are serine proteases Coagulation not triggered down intrinsic pathway

Answer 247

Primary driver of clotting cascade Initiated when TF on surface of cells (which normally do not come into contact with blood) are exposed to plasma clotting factors (TF + FVII -> TF-FVIIa complex) TF-FVIIa then activates FIX and FX FXa activates prothrombin (ProT) inefficiently leading to the generation of trace amounts of thrombin Thrombin can then activate FVIII and FV, which function as non-enzymatic cofactors for FIXa and FXa, respectively FIXa-FVIIIa catalyses the conversion of increased quantities of FXa FXa-FVa catalyse enhanced generation of thrombin (more efficient by bypassing initial step) Thrombin at the site of vessel damage converts fibrinogen (Fbg) to fibrin (Fbn), which is the molecular scaffold of a clot

Answer 248

Prothrombin-> thrombin | Thrombin converted fibrin to crosslinked fibrinq

Answer 249

FVa (nascent clotting factor activated by FXa), FVIIIa (secreted clotting factor activated by FIXa), platelets accelerate thrombin generation 10, 000 fold

Answer 250

Surface of platelet

Answer 251

Nascent clotting factors (II, VII, IX, X) with glutamic acid + vitamin K in liver Secreted clotting factors (II, VII, IX, X) and y-caboxyglutamic acid

Answer 252

Nascent clotting factors (II, VII, IX, X) with glutamic acid + vitamin K in liver (INHIBITED BY WARFARIN) Secreted clotting factors (II, VII, IX, X) and y-caboxyglutamic acid (INHIBITED BY WARFARIN- affect attachment to platelet membrane phospholipid)

Answer 253

HEPARIN= Immediate anticoagulation in venous thrombosis and pulmonary embolism WARFARIN= Long term anticoagulation following venous thrombosis and for treatment of atrial fibrillation

Answer 254

Accelerates the action of plasma inhibitor antithrombin (which is a direct inhibitor of thrombin and other proteinases) Factors VIII and V are activated by trace amount of thrombin and become cofactors so need to inactivate them

Answer 255

Direct inhibitor of thrombin and other proteinases (coagulation factors e.g. factor Xa) Loop goes into active sites of factor 10a and inhibits it Forms irreversible complex which is then cleared

Answer 256

``` Unfractured heparin (low molecular weight= 1500-25000) LMW heparin binds to thrombin and makes it inhibit factor 10a quicker ``` High molecular weight (5000-25000) heparin forms a bridge pulling 2a molecules together

Answer 257

Platelet count Bleeding time Platelet aggregation

Answer 258

APTT- intrinsic PT- extrinsic TCT/TT- being phased out Full blood count (platelets)

Answer 259

Initiates coagulation through FXII and detects abnormalities in Intrinsic and Common Pathways Test (with PT) for causes of bleeding disorders

Answer 260

Initiates coagulation through tissue factor and detects abnormalities in Extrinsic and Common Pathways Test (with APTT) to monitor heparin therapy in thrombosis Used for monitoring warfarin treatment in thrombosis

Answer 261

Add thrombin Being phased out Shows abnormality in the fibrinogen to fibrin conversion

Answer 262

Normally no interaction between plasminogen (plasma protein, zymogen) and tissue plasminogen activator tPA (plasma protein, proteinase) Interact when fibrin clot forms (both attracted to its surface) Plasmin starts to break down fibrin clot Fibrin degradation products (FDP) elevated in DIC

Answer 263

Therapeutical thrombolysis for myocardial infarction (clot blusters)

Answer 264

Small amount of factor VIIa producing a large amount of thrombin

Answer 265

Coagulation inhibitory mechanisms prevent this 1) Antithrombin (affects IXa, Xa and thrombin IIa) 2) Protein C anticoagulant pathway (with protein C and protein S) Deficiencies of antithrombin, protein C and protein S are important risk factors for thrombosis

Answer 266

``` Easy bruising Gum bleeding Frequent nosebleeds Bleeding after tooth extraction Post operative bleeding ``` Women= menorrhagia, post partum bleeding

Answer 267

Epistaxis not stopped by 10 mins compression or requiring medical attention/transfusion Cutaneous haemorrhage or bruising without apparent trauma (esp. multiple/large) Prolonged (>15 mins) bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound (spontaneous GI bleeding leading to anaemia) Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions of the uterus Heavy, prolonged or recurrent bleeding after surgery or dental extractions

Answer 268

Lack of a specific factor - Failure of production: congenital and acquired - Increased consumption/clearance Defective function of a specific factor - Genetic defect - Acquired defect- drugs, synthetic defect, inhibition

Answer 269

PLATELETS Thrombocytopenia Drugs VWF Von Willebrand disease THE VESSEL WALL Hereditary vascular disorders Scurvy, steroids, age

Answer 270

Failure of platelet production by megakaryocytes Shortened half life of platelets Increased pooling of platelets in an enlarged spleen (hypersplenism) and shortened half life

Answer 271

Bone marrow failure eg: leukaemia, B12 deficiency Accelerated clearance eg: immune (ITP), DIC

Answer 272

Autoimmune thrombocytopenic purpura (auto-ITP)= very common cause of thrombocytopenia Antiplatelet antibodies-> sensitised platelet-> sensitised platelet binds to macrophage

Answer 273

Hereditary absence of glycoproteins or storage granules

Answer 274

Glanzmann’s thrombasthenia= abnormality of platelets (contain defective/low levels of glycoprotein IIb/IIIa), rare coagulopathy Bernard Soulier syndrome= rare autosomal recessive coagulopathy (bleeding disorder) that causes a deficiency of glycoprotein Ib (GpIb), the receptor for von Willebrand factor Storage Pool disease= Storage pool deficiencies are a group of disorders caused by problems with platelet granules (alpha or beta granules)

Answer 275

Deficiency of VWF (Type 1 or 3) VWF with abnormal function (Type 2)

Answer 276

Binding to collagen and capturing platelets | Stabilising Factor VIII Factor VIII may be low if VWF is very low

Answer 277

Inherited (rare) hereditary haemorrhagic telangiectasia | Connective tissue disorder affect vessel wall

Answer 278

Scurvy Steroid therapy Ageing (senile purpura) Vasculitis

Answer 279

``` Immediate Prolonged bleeding from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma or surgery ```

Answer 280

A small red or purple spot caused by bleeding into the skin

Answer 281

Platelet count Bleeding time (PFA100 in lab) Assays of von Willebrand Factor Clinical observation

Answer 282

Deficiency of any coagulation factor results in a failure of thrombin generation and hence fibrin formation (from conversion from fibrinogen)

Answer 283

Failure to generate fibrin to stabilise platelet plug (problem iwth haemostasis) Loose plug insufficient to stop flow

Answer 284

The primary platelet plug is sufficient for small vessel injury But in larger vessels it will fall apart Fibrin formation stabilises the platelet plug

Answer 285

Deficiency of coagulation factor production - Hereditary (factor VIII/IX, haemophilia A/B) - Acquired (liver disease, dilution, anticoagulant drugs) Increased consumption - Acquired (DIC, autoantibodies)

Answer 286

Factor VIII and IX (Haemophilia) - > Severe but compatible with life - > Spontaneous joint and muscle bleeding Prothrombin (Factor II) -> Lethal Factor XI -> Bleed after trauma but not spontaneously Factor XII -> No excess bleeding at all

Answer 287

Deficiencies of coagulation factor production LIVER FAILURE Most coagulation factors are synthesised in the liver DILUTION Red cell transfusions no longer contain plasma Major transfusions require plasma as well as RBC and platelets

Answer 288

Disseminated intravascular coagulation (DIC)= increased consumption (an acquired coagulation disorder) Generalised activation of coagulation – Tissue factor Associated with sepsis, major tissue damage, inflammation Consumes and depletes coagulation factors Platelets consumed Activation of fibrinolysis depletes fibrinogen Deposition of fibrin in vessels causes organ failure

Answer 289

Superficial cuts do not bleed (platelets) Bruising is common, nosebleeds are rare Spontaneous bleeding is deep, into muscles and joints Bleeding after trauma may be delayed and is prolonged frequently restarts after stopping

Answer 290

Hallmark of haemophilia | Bleeding into joint spaces

Answer 291

PLATELET/VASCULAR Superficial bleeding into skin, mucosal membranes Bleeding immediate after injury COAGULATION Bleeding into deep tissues, muscles, joints Delayed but severe (often prolonged)

Answer 292

Screening tests (clotting screen) Factory assays Tests for inhibitors

Answer 293

``` Prolonged 85s (26-32 normally) ``` NB. PT normal

Answer 294

``` Mild factor deficiencies von Willebrand disease Factor XIII deficiency (cross linking) Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders (e.g. uraemia) (Thrombotic disorders) ```

Answer 295

Rare but disorders of fibrinolysis can cause abnormal bleeding ``` Hereditary= antiplasmin deficiency Acquired= drugs e.g. tPA an disseminated intravascular coagulation ```

Answer 296

Sex-linked recessive disorder

Answer 297

Autosomal disorder Type 2 (1) AD (dominant)- common Type 3 AR (recessive)

Answer 298

Autosomal recessive | Not very common

Answer 299

FAILURE OF PRODUCTION/FUNCTION Replace missing factor/platelets (prophylactic/therapeutic) Stop drugs IMMUNE DESTRUCTION Immunosuppression (e.g. prednisolone) Splenectomy for ITP INCREASED CONSUMPTION Treat cause Replace as necessary

Answer 300

Plasma= contains all coagulation factors Cryoprecipitate= rich in fibrinogen, FVIII, VWF, FXIII Factor concentrates= concentrates available for all factors except factor V Recombinant forms of FVIII and FIX are available

Answer 301

Pooled platelet concentrates available

Answer 302

``` Factor replacement therapy Platelet replacement therapy DDAVP Tranexamic acid Fibrin glue/spray ```

Answer 303

Vasopressin derivative 2-5 fold rise in VWF-VIII (VIII>vWF) Releases endogenous stores so only useful in mild disorders

Answer 304

Inhibits fibrinolysis Widely distributed – crosses placenta Low concentration in breast milk Useful adjunctive therapy (IV, oral, mouthwash)

Answer 305

DECREASED- Coagulation factors, platelets INCREASED- Fibrinolytic factors, anticoagulant proteins

Answer 306

DECREASED- Fibrinolytic factors, anticoagulant proteins INCREASED- Coagulation factors, platelets

Answer 307

1 pint (max. every 4 months)

Answer 308

Balance between benefits vs risks When no safer alternative available If massive bleeding (and plain fluids not sufficient) or if anaemia (and iron/B12/folate not appropriate)

Answer 309

A and B antigens on red cells formed by adding one or other sugar residue onto a common glycoprotein and fucose stem on red cell membrane (O has neither A nor B sugars- stem only)

Answer 310

Antigens are determined by corresponding genes Gene codes for enzyme which adds N-acetyl galactosamine to common glycoprotein and fucose stem B gene codes for enzyme which adds galactose A and B genes are co-dominant O gene is recessive

Answer 311

A and B genes are co-dominant | O gene is recessive

Answer 312

Person has antibodies against any antigen not present on own red cells IgM naturally occurs from birth (complete antibody- fully activates complement cascade to cause haemolysis of red cells)

Answer 313

IgM antibodies interact with corresponding antigen-> agglutination

Answer 314

``` A= A ag, anti-B ab B= B ag, anti-A ab O= nil ag, anti-A and anti-B ab AB= A and B ag, no ab ```

Answer 315

``` O= 47% A= 42% B= 8% AB= 3% ```

Answer 316

Plasma and cells

Answer 317

Test with known anti-A and anti-B reagents Select donor unit of same group (ag matter) X-match: patient's serum mixed with donor red cells should not react (react-> agglutinates then incompatible)

Answer 318

RhD | +ve (if have D antigen) or -ve (if not)

Answer 319

D codes for D antigen on red cell membrane (positive) | d codes for no antigen and is recessive (negative)

Answer 320

85% RhD positive | 15% RhD negative

Answer 321

Can make anti-D antibodies after they are exposed to the RhD antigen (by transfusion of RhD positive blood or in women pregnant with RhD positive fetus)

Answer 322

IgG antibodies

Answer 323

Patient must, in future, have RhD neg blood (otherwise his anti-D would react with RhD positive blood)

Answer 324

HDN= haemolytic disease of the newborn If RhD neg mother has anti-D and in next pregnancy fetus is RhD pos then mother's IgG anti-D antibodies can cross placenta This-> haemolysis of fetal red cells If severe: hydrops fetalis, death

Answer 325

Transfuse blood of same RhD group (no harm to give RhD neg to a pos patient but wasteful) Use O neg when emergency blood

Answer 326

Give O neg

Answer 327

Other antigens e.g. Rh group- C, c, E, e, Kell, Duffy, Kidd etc. 8% patients will form Ab to one or more of these antigens Once have formed antibody, must use corresponding antigen negative blood or else risk of delayed haemolytic reaction

Answer 328

Before each transfusion episode, test patient's blood sample for red cell antibodies So test ABO, RhD and do an 'antibody screen' of their plasma

Answer 329

A (AO) or B (BO) positive Woman passes an O Man passes an A or O

Answer 330

A positive | B negative

Answer 331

Use parts needed More efficient= less waste as patients don't need all components Some components degenerate quickly if stored as whole blood Red cells concentrated- as plasma removed which avoids fluid overloading patient

Answer 332

Anticoagulant

Answer 333

By centrifuging whole bag Red cells bottom Platelets middle Plasma top Then squeeze each layer into satellite bags and cut free (closed system)

Answer 334

Red cells Platelets Plasma

Answer 335

Fresh frozen plasma

Answer 336

FFP Cryoprecipitate Plasma for fractionation (not UK)- pools thousands of donors

Answer 337

1 unit from 1 donor- packed cells (fluid plasma removed) Shelf life 5 weeks; stored at 4oC Filter to remove clumps/debris Rarely need frozen red cells (poor recovery on thawing)

Answer 338

1 unit from 1 donor (300ml) can get small packs for children Stored at -30oC (frozen within 6h) of donation to preserve coag factors Shelf life 2 years Must thaw 20-30 mins before use (too hot-> proteins cook)

Answer 339

12-15ml/kg= usually 3 units Need to know blood group- no x-match just choose same group (as contains ABO abs which could-> haemolysis)

Answer 340

If bleeding and abnormal coag test results (PT, APTT) - Monitor response- clinically and by coag tests Reversal of warfarin (anticoagulant) e.g. for urgent surgery (if PCC not available) Other conditions occasionally NOT JUST TO REPLACE VOLUME/FLUID LOSS

Answer 341

From frozen plasma thawed at 4-8oC overnight residue remains Contains fibrinogen and factor VIII Same as FFP (store at -30oC for 2years) Standard dose= from 10 donors (5 in a pack)

Answer 342

If massive bleeding and fibrinogen very low Rarely hypofibrinogenaemia

Answer 343

1 pool from 4 donors (=standard adult dose_ or from 1 donor by apheresis (cell separator machine) Shelf life 5 days only (risk of bacterial infection) Store at 22oC (room temp) constantly agitated

Answer 344

Most haematology patients with bone marrow failure (if platelets <10 x10^9/L) Massive bleeding or acute DIC If very low platelets and patient needs surgery If for cardiac bypass and patient on anti-platelet drugs 1 pool is usually enough- rarely need more

Answer 345

``` Doesn't need platelets Needs FFP (fresh frozen plasma) with all the factors ```

Answer 346

Doesn't need platelets | Need FFP and cryoprecipitate (alone not enough)

Answer 347

Fractionated (like oil) Factor VIII and IX Immunoglobulins

Answer 348

For haemophilia A and B respectively (males) Factor VIII for von Willebrand's disease Heat treated- viral inactivation Recombinant factor VIII or IX alternatives increasingly used, but expensive

Answer 349

IM: Specific- tetanus, anti-D, rabies IM: Normal globulin- broad mix in population (e.g. HAV) IVIg- pre-op in patients with ITP or AIHA

Answer 350

``` 4.5% useful in burns, plasma exchange etc. Probably overused (not indicated in malnutrition) ``` 20% salt poor For certain severe liver and kidney conditions only

Answer 351

Weight limits Frequency of donations (limit) Test for infections and question risk behaviour (avoid high risk donors) Use voluntary, unpaid donors All blood tested for hep B, hep C, HIV, HTLV, syphilis and some tested for CMV (virus) or for HEV

Answer 352

Prion disease- vCJD

Answer 353

All plasma pooled to make fractionated products now obtained from USA (UK plasma- some used for FFP, the rest thrown away) All blood components have white cells filtered out (leucodepleted) in case white cells are essential for uptake of vCJD prion into brain to cause disease

Answer 354

3.4mg Fe per g of Hb

Answer 355

64-64.5 kDa

Answer 356

Transferrin with ferrittin provides Fe which goes to mitochondrion Heme produced in mitochondrion AAs-> ribosomes-> a and B chains form a2B2 globin -> haemoglobin (with heme)

Answer 357

CHROMOSOME 16- EMBRYO Gower 1 Portland Gower 2 CHROMOSOME 11- FETUS F CHROMOSOME 11- ADULT F A2 A

Answer 358

Hb A= a2b2 96-98% Hb A2= a2d 1.5-3.2% Hb F= a2y2 0.5%-0.8%

Answer 359

Deoxyhaemoglobin

Answer 360

Concentration of 2,3-DPG H+ concentration (pH) CO2 in RBCs Structure of Hb

Answer 361

Beta (B) thalassaemia

Answer 362

Deletion or mutation in B globin genes | Reduced or absent production of B globin chains

Answer 363

``` Mainly Mediterranean countries (Greece, Cyprus, Southern Italy) Arabian peninsula Iran Indian subcontinent Africa Southern China South-east Asia ```

Answer 364

Most thalassemias are inherited as recessive traits. Thalassemia is autosomal dominant in a very small percentage of beta thalassaemia cases A person who has only one mutated or defective gene typically does not experience symptoms and is called a carrier (thalassaemia trait)

Answer 365

FBC Microcytic hypochromic indices Increased RBCs relative to Hb FILM Target cells, poikilocytosis but no anisocytosis Hb EPS/ HPLC a-thal= normal HbA2 and HbF (+/- HbH) B-thal= raised HbA2 and raised HbF GLOBIN CHAIN SYNTHESIS/ DNA STUDIES Genetic analysis for B-thal mutations and Xmnl polymophism (in B) and a-thalassaemia genotype

Answer 366

``` Alpha chain precipitates Pappenheimer bodies (with Perls stain) ```

Answer 367

Anemia A pale and listless appearance. Poor appetite Dark urine (a sign that red blood cells are breaking down) Slowed growth and delayed puberty Jaundice (a yellowish colour of the skin or whites of the eyes) An enlarged spleen, liver, or heart

Answer 368

``` Transfuse patient as early as possible Phenotyped red cells Aim for pre-transfusion Hb 95-100g/L Regular transfusion 2-4 weekly If high requirement, consider splenectomy ```

Answer 369

Serum ferritin Liver biopsy T2 cardiac and hepatic MRI

Answer 370

>2500 associated with significantly increased complications Acute phase protein Check 3 monthly if transfused otherwise annually

Answer 371

Rarely performed

Answer 372

<20ms- increased risk of impaired LF function | Check annually or 3-6 monthly if cardiac dysfunction

Answer 373

Very common combo in SE Asia | Clinically variable in expression (can be as severe as b thalassaemia major)

Answer 374

Lack of awareness of the problems Lack of experience of health care providers Availability of blood Cost and compliance with iron chelation therapy Availability of and very high cost of bone marrow transplant

Answer 375

``` Counselling and health education for thalassaemics, family members and general public Extended family screening Pre-marital screening Discourage marriage between relatives Antenatal testing Pre-natal diagnosis (CVS) ```

Answer 376

Up to 10% Caribbeans and 25% sub-Saharan Africans carry sick gene 200,000 affected births annually worldwide

Answer 377

2 normal alpha chains 2 variant beta chains Point mutation at codon 6 of the gene for B globin Glutamic acid replaced by valine

Answer 378

Glutamic acid= polar, soluble Valine= non polar, insoluble Differences in polarity-> influences solubility of the molecule and the potential bonds that the globin chains can form

Answer 379

Deoxyhaemoglobin S is insoluble (due to valine substition) AHbS polymerises to form fibres called "tactoids" Allows deoxy Hb molecule to form intertetramer contacts (STABILISE STRUCTURE) and long polymers of HbS form within RBCs

Answer 380

AHbS polymerises to form fibres called tactoids in deoxyhaemoglobin S

Answer 381

Sickling of red cell - Distortion (polymerisation initially reversible with formation of oxyHbS)-> RIGID - Dehydration-> DEHYDRATED - Increased adherence-> ADHERENT Also membrane changes but aren't fully understood

Answer 382

Sickle cell anaemia and compound heterozygous states (C, SB thalassaemia) Genetically simple, clinically heterogenous NB. Sickle cell disease incorporates SCA and all other conditions that can lead to a disease syndrome due to sickling

Answer 383

1. Shortened red cell lifespan (120->20 days)- haemolysis ``` Anaemia Gall stones (due to increased red cell breakdown products) Aplastic crisis (parovirus B19) ``` 2. Blockage to microvascular circulation (vaso-occlusion) Tissue damage and necrosis (infarction due to clogging up of blood vessels by distorted, sticky red cells-> tissue death) Pain Dysfunction

Answer 384

Gilbert syndrome

Answer 385

Shortened red cell lifespan (120-> 20 days) Sickle-shape Anaemia is partly due to reduced erythropoietic drive as haemoglobin S is a low affinity haemoglobin

Answer 386

Hyposplenism -> infections because as patients age, spleen shrinks and splenic activity doesn't check infections it normally can (e.g. malaria or pneumococcal sepsis)

Answer 387

Dactylitis Avascular necrosis Osteomyelitis Particularly at risk= weight bearing femoral head and the fingers

Answer 388

Distinguished by the presence/absence of reticulocytes Both require urgent transfusion

Answer 389

Inflammation of a digit-> swelling into sausage shape and become painful

Answer 390

``` Bones/joints Skin Spleen Lungs Urinary tract Brain Eyes ```

Answer 391

Acute chest syndrome | Chronic damage- pulmonary hypertension

Answer 392

Haematuria (papillary necrosis) Impaired concentration of urine (hyposthenuria) Renal failure Priapism

Answer 393

Stroke | Cognitive impairment

Answer 394

Proliferative retinopathy

Answer 395

Most common cause of death in adults with SCD Medical emergency Present with crisis-> become hypoxic Infiltrates affecting both bases

Answer 396

Pulmonary hypertension correlates with the severity of haemolysis Probably because the free plasma haemoglobin resulting from intravascular haemolysis scavenges NO and causes vasoconstriction Associated with increased mortality

Answer 397

8% Most common 2-9 yrs involves major cerebral vessels

Answer 398

Symptoms rare before 3-6 months Dactylitis Splenic sequestration Infection (pneumococcal)

Answer 399

Switch from fetal to adult Hb synthesis | HbS predominates

Answer 400

``` Infection Exertion Dehydration Hypoxia Psychological stress ```

Answer 401

42 years in males | 48 years in females

Answer 402

``` 21% painful crises 14% chest syndrome 9% renal failure 7% infection 6% perioperative ```

Answer 403

``` General Prevention of early mortality Painful crisis Exchange transfusion Haemopoietic stem cell transplantation Induction of HbF ```

Answer 404

``` GENERAL Folic acid Penicillin Vaccination Monitor spleen size Blood transfusion for acute anaemic events, chest syndrome and stroke Pregnancy care ``` PREVENTION OF EARLY MORTALITY Prophylaxis against pneumococcal infection Monitoring for acute splenic sequestration

Answer 405

``` Pain relief (opioids) Hydration Keep warm Oxygen if hypoxic Exclude infection: Blood and urine cultures + CXR ```

Answer 406

Stroke | Acute chest syndrome

Answer 407

<16 yr with severe disease Survival 90-95% Cure 85-90%

Answer 408

Hydroxyurea | Butyrate

Answer 409

``` Hb low (6-8g/dl) Reticulocytes high (except in aplastic crisis) Film= sickled cells, boat cells, target cells and Howell Jolly bodies Solubility test ``` Definitive diagnosis= eletrophoresis or high performance liquid chromatography

Answer 410

In presence of a reducing agent oxyHb converted to deoxy Hb Solubility decreases Solution becomes turbid Does not differentiate AS from SS (SCA)

Answer 411

Electrophoresis or high performance liquid chromatography separates proteins according to charge On cellulose acetate membrane

Answer 412

``` Trait= A and S (heterozygous for Bs) Normal= A (homozygous for normal) SCA= S (homozygous for Bs) ```

Answer 413

HbAS Normal life expectancy and blood count Usually asymptomatic Rarely painless haematuria NB. caution: anaesthetic, high altitude, extreme exertion

Answer 414

All lineages of WBC reduced

Answer 415

Production of blood cells in marrow

Answer 416

NORMAL Polyclonal healthy/reactive MALIGNANT Abnormal/clonal Leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative

Answer 417

HSC= Haemopoietic stem cells Precursor to X (leads to Y) ``` Pre T (-> T cell) Pre B (-> B cell) BFU-E (-> RBCs) Meg-CFC (-> megakaryocyte/platelets) GM-CFC (-> granulocytes, monocytes) ```

Answer 418

From HSC Burst forming unit erythroid -> RBCs

Answer 419

From HSC Megakaryocytic colony forming cells -> Megakaryocyte/platelets

Answer 420

From HSC Granulocyte, monocyte colony forming cells -> Monocytes and granulocytes

Answer 421

``` BM Myeloblast Promelocyte Myelocyte Metamyelocyte ``` PERIPHERAL BLOOD Neutrophil

Answer 422

Patients have all stages of precursors NB. Can also be in patients who have received chemo and treated with GST

Answer 423

Cytokines influence differentiation and proliferation DNA directs this DNA damage-> cancer (leukaemia/lymphoma/myelomea

Answer 424

ERYTHROID Erythropoietin LYMPHOID IL2 MYELOID G-CSF M-CSF Damage-> leukaemia, lymphoma and myeloma

Answer 425

``` BM Myeloblasts Promelocytes Myelocytes Metamyelocytes ``` PERIPHERAL BLOOD Phagocytes= granulocytes (neutrophils, eosinophils, basophils) and monocytes

Answer 426

BM Lymphoblasts PERIPHERAL BLOOD T lymphocytes B lymphocytes NK cells

Answer 427

Increased cell production and/or cell survival | Decreased cell production and/or cell survival

Answer 428

``` Reaction= infection, inflammation Malignant= leukaemia, myeloproliferative ```

Answer 429

Failure of apoptosis (e.g. acquired cancer causing mutations in some lymphomas)

Answer 430

``` Impaired BM function B12 or folate deficiency BM failure (aplastic anaemia, post chemo, metastatic cancer, haematological cancer) ```

Answer 431

Immune breakdown

Answer 432

Immature cells proliferating and differentiating from stem cells in BM-> mature cells responding to infection in peripheral blood Haemopoietic cancers (leukaemia) in BM-> immature and mature cells in peripheral blood

Answer 433

Increased eosinophil number REACTIVE (normal haemopoiesis) Stimulated by inflammation Parasitic infestation Allergic disease (e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophlia) Neoplasms esp. Hodgkin's, T-cell NHL Hypereosinophilic syndrome Increased cytokine production (distant tumour, haemopoietic or non haemopoietic) PRIMARY (MALIGNANT) (abnormal haemopoiesis) Autonomous cell growth Cancers of haemopoietic cells Leukaemia (myeloid or lymphoid, chronic or acute) Myeloproliferative disorders Malignant chronic eosinophlic leukaemia (PDGFR fusion gene)

Answer 434

Malignant haematopoiesis HSCs have DNA damage-> increased proliferation-> increased number of platelets/granulocytes/monocytes

Answer 435

History and exam (e.g. for enlarged spleen) Haemoglobin and platelet count (usually not just WCC that is raised) Automated differential (recognises different WBCs) Examine blood film (automated machine may have failed to recognise different populations) WBCs abnormal, what about red cells/platelets? More than one kind of white cell affected? (Neuts/eos/monocytes/lymphocytes) Mature or immature cells?

Answer 436

MATURE 1) Lymphocytes= reactive (?viral) or primary (?chronic lymphocytic leukaemia) 2) All lineages or only one of neuts. eos, baso -> ?reactive infection MATURE/IMMATURE Neutrophils, myelocytes and basophils ?Chronic myeloid leukaemia IMMATURE Blasts and low Hb, low platelets ?Acute leukaemia

Answer 437

150-400 x 10^9/l

Answer 438

4-11 x 10^9/l

Answer 439

2.5-7.5 x 10^9/l

Answer 440

1.5-3.5 x 10^9/l

Answer 441

0.2-0.8 x 10^9/l

Answer 442

0.04-0.44 x 10^9/l

Answer 443

0.01-0.1 x 10^9/l

Answer 444

PHAGOCYTES Neutrophils Eosiphils Monocytes IMMUNE CELLS Lymphocytes

Answer 445

Present in BM, blood and tissues Life span 2-3 days in tissues (hours in PB) 50% circulating neutrophils are marginated (not counted in FBC)

Answer 446

Minutes-> demargination Hours-> early release from BM Days-> increased production (x3 in infection)

Answer 447

Neutrophilia >7.5x109/l Toxic granulation Vacuoles- cytoplasmic vacuolation

Answer 448

Chronic leukaemia Chronic myeloid leukaemia Neutrophilia and precursor cells (myelocytes)

Answer 449

Infection Tissue inflammation (e.g. colitis, pancreatitis) Physical stress, adrenaline, corticosteroids Underlying neoplasia Malignant neutrophilia Myeloproliferative disorders CML

Answer 450

Localised and systemic infections Acute bacterial, fungal, certain viral infections Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections

Answer 451

``` Rare but seen in certain infections and primary haematological disorders TB, brucella, typhoid Viral; CMV, varicella zoster Sarcoidosis Chronic myelomonocytic leukaemia (MDS) ``` NB. Sometime circulating blasts can be recognised as monocytes by machine So look at blood film

Answer 452

INFECTION Bacterial INFLAMMATION Auto-immune Tissue necrosis NEOPLASIA (cells not part of malignant population) All types

Answer 453

INFECTION Parasitic INFLAMMATION Allergic (asthma, atopy, drug reactions) NEOPLASIA (cells not part of malignant population) Hodgkin's NHL

Answer 454

Pox viruses

Answer 455

Chronic (TB, brucella)

Answer 456

``` MATURE (lymphocytes) Reactive (secondary) to infection Primary disorder E.g. CLL E.g. Autoimmune/inflammatory disease ``` IMMATURE (lymphoblasts) Primary disorder (leukaemia, lymphoma) E.g. Acute lymphoblastic leukaemia

Answer 457

PRIMARY Monoclonal lymphoid proliferation e.g. CLL SECONDARY (reactive) Polyclonal response to infection, chronic inflammation or underlying malignancy

Answer 458

``` EBV CMV Toxoplasma Infectious hepatitis Rubella Herpes infections ```

Answer 459

Infection Autoimmune disorders Neoplasia Sarcoidosis

Answer 460

EBV infection of B-lymphocytes via CD21 receptor Infected B-cell proliferates and expresses EBV associated antigens Cytotoxic T-lymphocyte response Acute infection resolved resulting in lifelong clinical infection

Answer 461

Morphology Immunophenotype Gene re-arrangement

Answer 462

Using (B cells) light chain restriction POLYCLONAL Kappa and lambda MONOCLONAL Kappa only or lambda only

Answer 463

Imuunoglobulin genes (Ig) and T cell receptor (TCR) genes undergo recombination in antigen stimulated B cells or T cells With primary monoclonal proliferation all daughter cells carry identical configuration of Ig, or TCR gene Detected by Southern Blot analysis

Answer 464

``` Parasitic infestation (schistosomiasis) Underlying lymphoma (HL or NHL) Allergic autoimmune disorder (asthma/urticaria) ```

Answer 465

Could be leukaemia (CML can have normal mature lymphocytes) Peripheral blood immunophenotype - If there is positive CD5 cells= typical feature of CLL

Answer 466

``` Positive CD5 cells Monoclonal cells (Kappa B cell results) ```

Answer 467

Raised WCC With anaemia and thrombocytopenia Marrow completely packed with blasts Normal cells not able to proliferate