Haematology

Question 1

What are lymphomas? Accumulate where causing what? Histologically divided into what 2 types?

Answer 1

Malignant proliferations of lymphocytes
Lymph nodes–> lymphadenopathy, also in peripheral blood or infiltrate organs
Hodgkins- have characteristic cells with mirror-like image nuclei called Reed- Sternberg cells
Non-Hodgkins- do not have characteristic cells, low grade= follicular, high grade= diffuse large B cell, very high grade= Burkitt’s

Question 2

Aetiology of lymphomas?

Answer 2

Primary immunodeficiency- ataxia telangiectasia, Wiscott- Aldrich syndrome
Secondary immunodeficiency- HIV, transplant recipients
Infection- EBV, human T-lymphotropic virus, helicobacter pylori
Autoimmune disorders e.g. SLE

Question 3

Signs and symptoms of lymphomas? Investigations into lymphomas?

Answer 3

Stroke, ulcers, nodal/ extra nodal disease, compression syndrome (lump compressing structures,) systemic B symptoms- lump, loss of appetite, weight loss, sweat
FBC, DM, lymph node biopsy, immunophenotyping(antigens,) cytogenetics (karyotyping- chromosomal abnormalities, FISH- translocations,) molecular genetics (PCR- insertions/ deletions,) history and examination, CXR, ECHO, PFT, WHO performance status

Question 4

Epidemiology and suggested role in pathogenesis? Further divided into what 2 types?

Answer 4

Male predominance, EBV suggested role
Peaks of incidence= teenagers and elderly
Classical (cHL)- hallmark= Reed-Sternberg cell with mirror- image nuclei, 90-95%
Nodular lymphocyte predominant HL (NLPHL)= Reed-Sternberg VARIANT, ‘popcorn cell’

Question 5

Risk factors for HL? Clinical presentation?

Answer 5

Affected sibling, EBV, SLE, obese, post-transplantation
Painless groin lymphadenopathy, young women= cough due to mediastinal lymphadenopathy
B symptoms= weight loss, fever, night sweats
Emergency= infection, SVC obstruction with increased JVP, sensation of fullness in head, dyspnoea, blackouts, facial oedema

Question 6

Diagnosis of HL?

Answer 6

CT/MRI of chest, abdomen and pelvis for staging (Ann Arbor), lymph node excision/ bone marrow biopsy- popcorn cells
Bloods: high ESR or low Hb- worse prognosis
Immunophenotyping, cytogenetics, PET scan

Question 7

Staging of HL (Ann Arbor)? Each stage what or what?

Answer 7

I= confined to single lymph node region, II= two or more nodal areas on same side of diaphragm, III= nodes on both sides of diaphragm, IV= spread beyond lymph nodes e.g. liver/ bone marrow
A or B- A= no systemic symptoms other than pruritus (severe itching of skin,)
B= B symptoms- fever, weight loss and night sweats

Question 8

Treatment of HL? Complications of radio and chemotherapy?

Answer 8

Combination chemotherapy- ABVD: A- adriamycin, B- bleomycin, V- vinblastine, D- dacarbazine
I-A to II-A= short course ABVD followed by RT
II-A to IV-B= longer course ABVD
Radio= increases risk of second malignancies- solid tumours esp in lung, breast, melanoma, stomach, sarcoma and thyroid, increased risk of IHD, hypothyroidism and lung fibrosis
Chemo= myelosuppression, nausea, alopecia and infection, infertility

Question 9

Epidemiology and risk factor for N-HL?

Answer 9

All lymphomas without Reed-Sternberg cells, around 80%= B-cell origin, diffuse large B-cell= commonest, 20%= T-cell
More varied in terms of presentation, sub-types, treatments and outcomes, not all centre on nodes, strong link with EBV and Burkitts lymphoma
Family history= minor increase in risk

Question 10

Presentation of N-HL?

Answer 10

Nodal disease (75%) e.g. superficial lymphadenopathy
Extranodal (25%): skin- esp T-cell lymphoma, oropharynx, gut, small bowel, bone, CNS and lungs
Systemic B symptoms
Pancocytopenia- anaemia, infection and bleeding

Question 11

N-HL classified into what 2 grades? Presents and curable?

Answer 11

Low/indolent grade- e.g. follicular, slow growing, usually advanced at presentation, incurable, median survival= 9-11 years
High grade- e.g. diffuse large B-cell, usually nodal presentation, 1/3 cases have extra nodal involvement

Question 12

Diagnosis of N-HL?

Answer 12

Raised lactose dehydrogenase= worse prognosis, lymph node excision/ bone marrow biopsy- not see R-S cells/ popcorn cells
Marrow and node biopsy for classification, CT/MRI of chest, abdomen and pelvis for staging, immunophenotyping, cytogenetics

Question 13

Treatment of N-HL?

Answer 13

R-CHOP regimen: 
R- rituximab (MAb- minimal side effects) 
C- cyclophosphamide 
H-hydroxy-daunorubicin 
O-vincristine (oncovin brand) 
P-prednisolone

Question 14

Rituximab targets what? Treatment for grades of N-HL? What is Burkitts lymphoma?

Answer 14

MAb targeting CD20 expressed on B cell surface
Low grade= none may be needed, radio may be curative in localised disease
High grade= early- 3 months R-CHOP with radiotherapy, late= 6 months R-CHOP regimen with radiotherapy
Usually B cells with jaw lymphadenopathy in children

Question 15

Epidemiology of myeloma?

Answer 15

Cancer of differentiated B lymphocytes known as plasma cells, accumulation of malignant plasma cells in bone marrow–> progressive bone marrow failure
Produce excess of one type of Ig= monoclonal paraprotein
IgG(55%), IgA(20%), rarely IgM and IgD
Others= low–> immunoparesis, bone disease, hypercalcaemia, renal failure
Peak age= 70 years, more common in Afro-Caribeeans than caucasians

Question 16

Clinical presentation of myeloma? 2 things activate osteoclasts? Inhibiting osteoblasts?

Answer 16

OLD CRAB
Old age, calcium elevated, renal failure- nephrotic syndrome, Igs deposit in organs–> thirst from kidneys, anaemia- neutropenia or thrombocytopenia, bone lytic lesions- back pain= osteoclasts activated–> increased breakdown and lytic lesions
RANK ligand and IL-3
HGF and Dkk-1
Recurrent bacterial infections due to neutropenia, healthy= may cause high neutrophil count

Question 17

Diagnosis of myeloma? Diagnosis requires?

Answer 17

Blood: normocytic normochromic anaemia, raised ESR, Rouleaux formation on blood film
U&Es= high calcium, high alkaline phosphatase, Bence-jones protein in urine
PLAIN X-ray- lytic ‘punched out lesions: pepper-pot skull, vertebral collapse
Serum and urine electrophoresis- B2- macro globulin present and prognostic, fractures and osteoporosis
Monoclonal protein band in serum or urine, increased plasma cells on bone marrow biopsy, hypercalcaemia/ renal failure/ anaemia, bone lesions on skeletal survey

Question 18

Treatment of myeloma?

Answer 18

Bone pain= analgesia, avoid NSAIDs due to renal risk
Bisphosphonates e.g. zolendronate- reduce fracture rates and bone pain
Anaemia= RBC transfusion and erythropoietin
Rehydration of 3L/day
Renal dialysis- treat acute renal failure
Broad-spectrum antibiotics to treat infections quickly
Chemo= CTD- cyclophosphamide, thalidomide and dexamethasone, max 8 cycles for less fit people
VAD- in fitter people, max 6 cycles
Stem cell transplant

Question 19

4 main subtypes of leukaemia? What is leukaemia?

Answer 19

Acute lymphoblastic, acute myeloid (AML,) chronic myeloid (CML,) and chronic lymphocytic (CLL)
Presence of rapidly proliferating immature blast blood cells (can be pre-cursors of RBCs, platelets or white cells) in bone marrow that are non functional i.e. defective

Question 20

2 issues posed by leukaemia? Age of leukaemia in general?

Answer 20

Dividing rapidly but serve no function, so wasting energy, less available for making useful functional cells
Due to rapid replication, these cells take up lot of space within bone marrow, meaning little space and also food for other cells to grow
When no space in BM, leukaemia cells will be present in blood too
At any age, type varies with age, all mainly seen in childhood and CLL= elderly disease

Question 21

Epidemiology of acute myeloid leukaemia (AML)?

Answer 21

Neoplastic proliferation of blast cells derived from marrow myeloid–> basophils, neutrophils and eosinophils
Progresses rapidly with death in 2 months if untreated, commonest acute leukaemia of adults
Associated with radiation and syndromes such as Down’s

Question 22

Clinical presentation of acute myeloid leukaemia?

Answer 22

Marrow failure: anaemia- low Hb: breathlessness, fatigue, angina and claudication, pallor, cardiac flow murmur
Infection- low WCC–> infections, fever, mouth ulcers
Bleeding- low platelets–> bleeding and bruising
Hepatomegaly and splenomegaly due to infiltration, gum hypertrophy, DIC occurs in subtype of AML where release of thromboplastin

Question 23

Diagnosis and complications of acute myeloid leukaemia?

Answer 23

WCC often raised, but can be normal/ low, may be few blast cells in peripheral blood so diagnosis depends on bone marrow biopsy, differentiation from all based on: immunophenotyping and molecular methods
Infection- alert to septicaemia, causes common organisms to present oddly, with few antibodies being made

Question 24

Treatment for AML?

Answer 24

Blood and platelet transfusions, neutropenia= prophylactic antivirals, antibacterial and antifungals, allopurinol- prevents tumour lysis syndrome, IV fluids- Hickman line, chemotherapy, marrow transplantation

Question 25

Epidemiology of chronic myeloid leukaemia (CML)?

Answer 25

Most exclusively disease of adults, uncontrolled clonal proliferation of myeloid cells, occurs most often between 40-60 years, slight male predominance, rare in childhood, more than 80%= Philadelphia chromosome forms fusion gene BCR/ ABL on chromosome 22= tyrosine kinase activity stimulating cell division

Question 26

Clinical presentation of CML?

Answer 26

Symptomatic anaemia e.g. SOB, abdominal discomfort due to splenomegaly, weight loss, tiredness, pallor, fever and sweats in absence of infection, features of gout due to purine breakdown, bleeding due to platelet dysfunction

Question 27

Diagnosis of CML? Treatment of CML?

Answer 27

Blood count: very high WCC- whole spectrum of myeloid cells i.e. increased; neutrophils, myelocytes, basophils and eosinophils, low Hb- normochromic and normocytic, low platelets or normal or raised, bone marrow aspirate: hyper cellular (increased cells) Oral imatinib- specific BCR/ABL tyrosine kinase inhibitor, stem cell transplant

Question 28

Epidemiology of chronic lymphocytic leukaemia (CLL)?

Answer 28

Most common leukaemia, occurs predominantly in later life, accumulation of mature B cells escaped programmed cell death and undergone cell-cycle arrest Mutations, trisomies and deletions influence risk, pneumonia may be triggering event

Question 29

Clinical presentation of CLL?

Answer 29

Often no symptoms, presenting as surprised on routine FBC, may be anaemic or infection prone, severe= weight loss, sweats and anorexia, hepatosplenomegaly, enlarged rubbery, non-tender nodes

Question 30

Diagnosis and complications of CLL?

Answer 30

Normal or low Hb, raised WCC with very high lymphocytes, blood film: smudge cells may be seen in vitro Autoimmune haemolysis- increased infection risk due to low IgG; bacterial and viral especially herpes zoster, marrow failure

Question 31

Progression and prognosis of CLL? Tx?

Answer 31

Many stable for years and may even regress, death= often due to complication of infection, may transform--> aggressive lymphoma= Richter's syndrome 1/3 will never progress, 1/3 progress slowly, 1/3 progress actively Blood transfusions, human IV IGs, chemotherapy or radiotherapy, stem cell transplant

Question 32

What is anaemia?

Answer 32

Decrease in Hb in the blood below reference level for age and sex of individual Either due to low red cell mass (RCM) or increased plasma volume May be due to reduced production from BM or increased loss of RBCs by spleen, liver, BM and blood loss and has many causes

Question 33

What test is to whether bone marrow production is the issue? Reduction in plasma volume will lead to what? Various anaemia types classified by what? 3 major types?

Answer 33

Reticulocyte count- low= production issue, high= removal issue Falsely high Hb- seen in dehydration Mean corpuscular volume (MCV)- average volume of RBCs Hypochromic microcytic- low MCV Normochromic normocytic- normal MCV Macrocytic- high MCV

Question 34

Consequences of anaemia? Pathological consequences?

Answer 34

Reduced O2 transport, tissue hypoxia, compensatory changes: increased tissue perfusion, increased O2 transfer to tissues, increased RBC production Myocardial fatty change, fatty change in liver, aggravates angina and claudication, skin and nail atrophic changes, CNS cell death (cortex and basal ganglia)

Question 35

Non-specific symptoms of anaemia? Signs?

Answer 35

Fatigue, headaches, faintness, dyspnoea and breathlessness, angina- if pre-existing coronary disease, anorexia, intermittent claudication, palpitations May be absent even in severe anaemia, pallor, tachycardia, systolic flow murmur, cardiac failure

Question 36

3 main causes of microcytic anaemia? Rarely from what? MCV value?

Answer 36

Iron deficiency anaemia- most common, anaemia of chronic disease, thalassaemia Congenital sideroblastic anaemia, lead poisoning <80

Question 37

Iron deficiency from what causes? Average daily intake? % absorbed in duodenum? How is it absorbed?

Answer 37

Diet, menorrhagia, hookworm TB, RA, HF 15-20mg, AT into intestinal epithelial cells by HCP1, some into ferritin, not ferritin= to plasma protein transferrin, to BM into new erythrocytes, majority= Hb Rest= in reticuloendothelial cells, hepatocytes and skeletal muscles cells either as ferritin/ haemosiderin

Question 38

Signs of iron deficiency anaemia? Diagnosis?

Answer 38

Brittle hair and nails, atrophic glossitis- tongue inflammation, kolionychia- spoon shaped nails, angular stomatitis- inflammation of corners of mouth Variation in RBC shape and size Low serum ferrite Low serum iron, transferrin saturation< 19%, total iron-binding capacity (TIBC) rises compared to normal Reticulocyte count low Number of transferrin receptors increases Further GI investigations

Question 39

Tx of iron deficiency anaemia? Side effects?

Answer 39

Find and treat cause, oral iron e.g. ferrous sulfate= nausea, abdominal discomfort, diarrhoea/ constipation and black stools Ferrous gluconate if SEs bad Parenteral iron e.g. IV iron/ deep intramuscular iron in extreme cases e.g. severe malabsorption

Question 40

Anaemia of chronic disease from what disease? Can cause what?

Answer 40

CKD, rheumatoid arthritis, lupus, cancer | Shortening of red blood cell life/ reducing red blood cell production

Question 41

Main causes of normocytic anaemia? MCV value?

Answer 41

Acute blood loss, anaemia of chronic disease, endocrine disorders such as hypopituitarism, hypothyroidism and hypoadrenalism, renal failure, pregnancy 80-100 = MCV

Question 42

Main causes of macrocytic anaemia? MCV value? What is megaloblastic anaemia? Non-megaloblastic anaemia?

Answer 42

B12 deficiency(pernicious,) folate deficiency, alcohol excess MCV> 100 Inhibition of DNA synthesis i.e. B12 and folate deficiency anaemias Where erythroblasts are normal i.e. normoblastic

Question 43

Causes of folate deficiency, absorbed where? Found in what foods? Diagnosis and Tx?

Answer 43

Poor folate diet, malabsorption, pregnancy, anti-folate drugs (methotrexate) , jejunum Green veg, nuts, yeast and liver Blood film= macrocytic, erythrocyte folate level Tx= folic acid supplementation and treat underlying cause, consider supplementation during pregnancy

Question 44

Vitamin B12 absorbed where bound to what? Found in what foods? Causes of deficiency? Epidemiology? Specific sign?

Answer 44

Terminal ileum bound to intrinsic factor Meat, fish, dairy products, but not plants Atrophic gastritis, gastrectomy, Crohn's, coeliac, pernicious anaemia= parietal cells of stomach attacked so intrinsic factor not produced Common in elderly, fair-haired, blue-eyed and blood group A, more females than males Neurological problems

Question 45

What is specific for pernicious diagnosis? Investigations for pernicious anaemia, Tx, complications?

Answer 45

Intrinsic factor antibodies Blood film- macrocytic Autoantibody screen- check for IF antibodies Vitamin B12 tablets/ injections, not folic acid, dietary cause= oral B12, IM hydroxocobalamin Heart failure, angina, neuropathy

Question 46

When does haemolytic anaemia occur? Main causes? Signs and symptoms? Investigations? Tx?

Answer 46

When RBCs are destroyed before 120 days Membranopathies, enzymmopathies, haemoglobinopathies, autoimmune, infections, secondary to systemic disease Gallstones, signs: jaundice, leg ulcers, splenomegaly, signs of underlying disease FBC= reduced Hb, increased reticulocytes, Schistocytes on blood film Tx= folate and iron supplementation, immunosuppressives, splenectomy

Question 47

What does bone marrow failure result in(aplastic anaemia)? Causes? Signs/ symptoms? Investigations? Tx?

Answer 47

Reduced number of pluripotent stem cells, lack of haemopoiesis Congenital, acquired, cytotoxic drugs/ radiation, infections Increased infection susceptibility, bruising, bleeding- nose and gums esp FBC= pancytopenia, reticulocyte count- low, bone marrow biopsy- hepatocellular marrow with increased fat spaces Removal of causative agent, blood/ platelet transfusion, bone marrow transplant, immunosuppressive therapy

Question 48

What is polycythaemia? Primary causes? Secondary causes?

Answer 48

Increased Hb, packed cell volume (PCV,) and RBCs Increases bone marrow cells sensitivity to EPo= increased RBC production= polycthaemia rubra vera- genetic mutation in JAK2 gene, primary familial and congenital polycthaemia- mutation in EPOR gene More RBCs due to more circulating EPO= chronic hypoxia, poor O2 delivery, abnormal RBC structure and tumours increased EPO levels

Question 49

Symptoms of polycythaemia? Investigations and Tx?

Answer 49

May present with no symptoms, easy bleeding/ bruising, fatigue, dizziness, headaches etc FBC, bone marrow biopsy, genetic testing for JAK2 gene Blood letting, aspirin- rubra vera Secondary= treat the cause

Question 50

3 categories of red cell disorders?

Answer 50

Haemoglobinopathy- sickle cell disease, thalassemia Membranopathy- spherocytosis, elliptocytosis Enzymopathy- glucose 6 phosphate deficiency

Question 51

What is sickle cell anaemia? How do cells become sickled? Precipitated by what? Why can patients feel well despite being anaemic?

Answer 51

Autosomal recessive disease, commoner in Afro-Caribbean Point mutation of B globin gene (valine to glutamine) resulting in HS variant HbS= insoluble and polymerises when deoxygenated, become rigid, lose membrane flexibility--> shortened lifespan (haemolysis) and impaired passage through microcirculation Infection, dehydration, cold, acidosis or hypoxia HbS releases O2 to tissues more readily than normal

Question 52

Presentation of SCA in heterozygous state? In homozygous state?

Answer 52

Symptom free except in hypoxia- vasoconstriction-occlusive events may occur Vaso-occlusive events- acute pain in hands and feet (dactylitis), long bones in adults, CNS infarction, acute chest syndrome, pulmonary hypertension, anaemia- acute drop due to: splenic sequestration, bone marrow aplasia

Question 53

Long-term issues of SCA?

Answer 53

Growth and development- short until adulthood, below normal weight, sexual maturation delayed Avascular necrosis of hips and shoulders, compression of vertebrae and shortening of bones in hands and feet Osteomyelitis- due to bacteria Cardiac issues- cardiomegaly, arrhythmias, MI Neurological- TIA, fits, cerebral infarction and coma Chronic hepatomegaly, nephritis, retinopathy, spontaneous abortion

Question 54

Diagnosis and Tx of SCA?

Answer 54

Neonates= blood/ heel prick test, Hb and reticulocyte count, sickled erythrocytes on blood film, Hb electrophoresis for dx, HbSS present and absent HbA Aggressive analgesia, treat cause, fluids, folic acid, transfuse with falling Hb Transfusion, stem cell transplant, hydroxycarbamide Hypsplenic= prophylactic acid Abx, pneumococcal and meningococcal vaccination

Question 55

What is thalassaemia? Precipitation of global chains in red cell precursors and in mature red cells causes what? 2 types? Common where?

Answer 55

Autosomal recessive disease of unbalance Hb synthesis within red cell precursors/ mature red cells, with under production/ no production of one global chain Ineffective erythropoiesis and haemolysis Alpha and Beta From the Mediterranean to the Far East

Question 56

Epidemiology of Beta thalassaemia? Pathophysiology?

Answer 56

Little or no B chain production--> excess alpha chains= combine with whatever delta and gamma chains produced--> increased HbA2 (Hb delta) and HbF (Hb gamma), caused by over 200 genetic defects Defects normally point mutations--> defects in transcription, RNA splicing and modification, translation via frame shifts and nonsense codons--> highly unstable B-globin cannot be utilised Heterozygois= asymptomatic microcytosis with or without mild anaemia

Question 57

3 types of Beta thalassaemia?

Answer 57

B-thal minor- mild/absent anaemia, low MCV and MCH, iron stores and ferritin normal B-thal intermedia- moderate anaemia, transfusions not required, splenomegaly, bone abnormalities, recurrent leg ulcers and gallstones B-thal major= homozygous, presents in 1st year of life with severe anaemia, failure to thrive and chronic infections, bony abnormalities, hepatosplenomegaly

Question 58

Investigations and treatment for Beta thalassaemia?

Answer 58

FBC and film hypo chromic and microcytic anaemia, irregular and pale RBCs, increased reticulocytes and nucleated RBCs, diagnosis by Hb electrophoresis- shows increased HbF and absent/ low HbA Blood transfusions= 2-4 weekly Give iron chelation to decrease iron loading, ascorbic acid= increased urinary excretion of iron Long term folic acid Other= bone health, endocrine supplements and psychological support, promote fitness and healthy diet

Question 59

How many genes control production of alpha globin chains? Thalassaemia caused by what? 4,3,2 and 1 deletion causes what? Carriers protected from what?

Answer 59

4 genes control production, caused by gene deletions 4 deletions= no chain synthesis, Hb Barts cannot carry oxygen and is incompatible with life- infants= stillborn, pale, oedematous with huge livers and spleens 3 deletions= common in parts of Asia, low levels of HbA and Hb Barts, severe haemolytic anaemia and splenomegaly, sometimes transfusion dependent 2 deletions= asymptomatic with possible mild anaemia, 1 deletion= blood picture normal Falciparum malaria

Question 60

What are membranopathies? Symptoms? Investigations and Tx?

Answer 60

Autosomal dominant condition--> deficiency in protein use to make red cell membrane--> deformed cells-> trapped in spleen (extravascular haemolysis) Spherocytosis (vertical deformity,) elliptocytosis (horizontal deformity) Neonatal jaundice and haemolytic anaemia exacerbated during infection (splenomegaly), excess bilirubin= gallstones FBC and reticulocytes count, blood film; osmotic fragility tests (RBCs show fragility in hypotonic solutions) Tx= folic acid and splenectomy

Question 61

Epidemiology of glucose-6-phosphate deficiency? Pathophysiology?

Answer 61

Heterogenous X-linked- more common in males, Africa, around the Mediterranean and in the Middle East and SE Asia Presents with haemolytic anaemia- mutations mostly single amino acid substitutions G6PD is vital for reaction necessary for RBCs, provide NADPH which is used with glutathione to protect RBC from oxidative damage from compounds like H2O2--> reduced RBC lifespan

Question 62

Presentation of G6PD deficiency, diagnosis and Tx?

Answer 62

Most asymptomatic, may get oxidative crisis due to reduction in glutathione production, precipitated by: acute drug-induced haemolysis e.g. primaquine, sulphonamides, nitrofurantoin, quinolones, dapsone In attacks= rapid anaemia, jaundice Chronic haemolytic anaemia Neonatal jaundice Blood film= bite and blister cells, increased reticulocytes Diagnosis= enzyme assay G6PD levels= low Tx= stop offending drugs, blood transfusion may be lifesaving, splenectomy= not usually helpful

Question 63

What are platelets regulated by produced by the liver? Binds to what receptors? Lifespan and normal count of platelets? Removed by what organ?

Answer 63

Thrombopoietin--> platelet and MK receptors Decrease in platelets= less bound TPO= more TPO able to bind to MK= increased platelet production 7-10 days, normal count= 150-400 x10 9/L Spleen

Question 64

Important platelet receptors?

Answer 64

``` Thromboxane A2 (TXA2)- from arachidonic acid in platelets via cyclooxyrgenase (COX-1)--> platelet aggregation and vasoconstriction P2Y12- activated by ADP, amplifies platelet activation and helps activate glycoprotein IIb/ IIIa Glycoprotein IIb/ IIIa= fibrinogen and von Willebrand Factor receptor, aids platelet adherence and aggregation ```

Question 65

Causes of platelet dysfunction?

Answer 65

Reduced platelet number: decrease in production, increase in destruction Normal numbers but reduced function: congenital abnormality in platelet function, medication e.g. aspirin, von Willebrand disease, uraemia

Question 66

What is thrombocytopenia? What can cause decreased production? Increased destruction?

Answer 66

Deficiency of platelets in the blood Congenital- malfunctioning platelets in BM Infiltration of BM- leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis Low B12/ folate/ reduced TPO, medication, toxins e.g. alcohol, infections e.g. HIV/ TB, aplastic anaemia Myelodysplasia Autoimmune- immune thrombocytopenia purpura (ITP); primary/ secondary Hypersplenism- portal hypertension and splenomegaly, drug related immune destruction e.g. heparin induced thrombocytopenia Platelet consumption- disseminated intravascular coagulopathy (DIC), thrombotic thrombocytopenia purport (TTP)

Question 67

Is ITP or TTP more common? Antibodies coating the platelets are removed by binding to what receptors on macrophages? Clinical features? Investigations? Tx?

Answer 67

ITP Fc receptors on macrophages Easy bruising, purpura, epistaxis/ menorrhagia Reduced platelets so normal/ increased megakaryocytes, may have detection of platelet autoantibodies Corticosteroids i.e. prednisolone, splenectomy, IV IG, anti D

Question 68

Physiology of thrombotic thrombocytopenia purpura? Clinical features? Investigation? Tx?

Answer 68

Microvascular clots form in small vessels in body, resulting in low platelet count and organ damage Easy bruising, purpura, epistaxis/ menorrhagia Reduced platelets so normal/ increased megakaryocytes Tx= plasma exchange and immunosuppression, IV methylprednisolone, IV rituximab

Question 69

HbA made of what? HbF? HbA2? %s of each in an adult?

Answer 69

``` HbA= haem + 2 alpha chains + 2 beta chains HbF(foetal)= haem + 2 alpha chains and 2 gamma chains Hb delta (HbA2)= haem + 2 alpha chains and 2 delta chains HbA= 97%, HbA2= 2%, HbF= 1% ```

Question 70

Patients that might be over anti coagulated? Why may this be? Symptoms? Assessing bleeding x2?

Answer 70

Vit K antagonists e.g. warfarin, NOACs e.g. apixiban Bad pt compliance, artificial valves, new/ interacting drugs Brusing, bleeding, melena, epistaxis, hematemesis, haemoptysis APTT (activated partial thromboplastin time)= intrinsic pathway PTT(prothrombin time)= extrinsic pathway

Question 71

What is disseminated intravascular coagulation? (DIC) Causes? Tx?

Answer 71

Generation of fibrin+ consumption of platelets/ coagulation factors causing sec activation of fibrinolysis Malignancy, septicaemia, obstetric causes, trauma, infections, haemolytic transfusion reactions, liver disease Tx= treat underlying cause- maintain blood volume and tissue perfusion, may need transfusions, activated protein C Fresh frozen plasma (FFP) to replace coag factors Cryoprecipitate to replace fibrinogen and some coagulation factors Red cell transfusion in bleeding patients

Question 72

2 haemophilia types? Epidemiology? Symptoms? PTT and APTT times and pathways?

Answer 72

``` A= factor 8 deficiency, Tx= IV factor 8 B= factor 9 deficiency X-linked recessive, A= more common Anything associated with bleeding Normal PTT but prolonged APTT PTT--> extrinsic pathway, APTT--> intrinsic pathway ```

Question 73

What is tumour lysis syndrome? At risk patients?

Answer 73

Malignant cells breakdown resulting in euro, cardio and renal complications High uric acid, hyperkalaemia, hyperphoshatemia, hypocalcaemia High tumour burden, high grade disease i.e. rapid cell turnover, pre-existing renal impairment, increasing age, drugs that increase uric acid formation e.g. alcohol Tx= aggressive hydration, allopurinol or rasburicase= reduce uric acid production, monitor electrolytes, refer to dialysis if required

Question 74

What are counted as haematological emergencies? What is neutropenia defined as? At risk patients?

Answer 74

Febrile neutropenia, acute sickle cell crisis, chest crisis, spinal cord compression Temp above 38 degrees, absolute neutrophil count< 1.0 x10 9/L Chemo less than 6 weeks ago, stem cell trans/ high dose chemo within last year, aplastic anaemia, autoimmune disease, leukaemia People on methotrexate, carbimazole and clozapine

Question 75

Presentation of neutropenia and management?

Answer 75

Pyrexia, malaise, sweats/ rigors, cough, sore throat, abode pain or diarrhoea, pain/ erythema around central venous catheter, tachycardia, hypotension and raised resp rate Broad spec IV antibiotics without waiting for results within 1 hour of admission Do not catheterise

Question 76

Patients at risk of malignant spinal cord compression? Clinical presentation?

Answer 76

Bone metastasis and vertebral collapse, local tumour extension, deposition of malignant cells within cord Myeloma, lymphoma Back pain, weakness/ numbness in legs, inability to control bladder/ bowel, saddle paraesthesia, uni/bilateral leg weakness, decreased perianal sensation and anal tone, acute= tone and reflexes reduced

Question 77

Management of malignant spinal cord compression?

Answer 77

Time= nerves, strict bed rest, high dose steroid e.g. oral dexamethasone, analgesia, urgent MRI of whole spine

Question 78

What is hyper viscosity syndrome? Usually due to high levels of what? Seen in what conditions? Can be due to what? Results in what?

Answer 78

Increase in blood viscosity (thickness,) high levels of Igs Multiple myeloma and Waldenstrom macroglobulinaemia Due to high cell numbers e.g. leukaemia or polycthaemia --> vascular stasis and hypo perfusion

Question 79

Clinical presentation of hyperviscosity syndrome?

Answer 79

Mucosal bleeding, visual change due to hypo perfusion to retina, neurological disturbance due to brain hypo perfusion: vertigo, hearing loss, paraesthesia, ataxia, headache, seizure or stupor, SOB, fatigue, bruising/ bleeding, dilated retinal veins, ataxia/ nystagmus, evidence of volume overload

Question 80

Diagnosis and Tx of hyperviscosity syndrome?

Answer 80

Plasma viscosity level, CT head to exclude other causes of neurological signs, Ig levels, FBC Keep hydrated, avoid transfusion= thicker, plasmapheresis- remove circulating Igs to decrease serum viscosity, symptoms will improve