Haematology

Question 1

Sickle cell disease
- Definition
- Pathophysiology
- Risk factors (2)
- Symptoms (2)
- Signs (7)
- DD (4)
- Investigations (8)
- Management - acute crisis, prophylaxis
- Complications (9)
- Extra facts

Answer 1

• Definition: an inherited hemoglobinopathy where autosomal recessive mutation in beta globin gene which encodes haemoglobin beta subunit. Life expectancy is 58 years
• Pathophysiology: Normal haemoglobin has 4 globin chains + 4 haem molecules - Normal HbA has 2 alpha and 2 beta chains. GAG to GTG nucleic acid substitution causing glutamic acid to valine which results in a HbS allele. If one allele then a carrier (HbAS) (assymp) and if homozygous (HbSS) then sickle cell disease. In deoxygenated state HbS tetramers bind to each other and can polymerise distorting the shape + becomes rigid. The abnormal shape makes it more fragile leading to haemolytic anaemias
• Risk factors: black african/caribbean, asian, STRONG family history
• Symptoms: intermittent acute pain vaso-occlusion (back, legs, knee) precipitated by hypoxia/infection, exercise, dehydration. Dactylitis
• Signs: pallor, fatigue (anaemia), jaundice (hemolysis), fever, digital redness, tachycardia, tachypnoea
• DD: gout, pancreatitis, appendicitis, cholecystitis
• Investigations: antenatal screening, newborn blood spot test, haemoglobin electrophoresis (appears around 6 months when HbF decreases), high performance liquid chromatography, blood film (nucleated rbc, howell jolly bodies, sickle shaped rbcs), bloods (fbc, reticulocyte count, iron studies), xray long bones (infarctions), cxr (infiltrates may indicate acute chest syndrome)
• Management:
  Sickle cell/ Acute pain crisis - paracet/nsaids, fluids, oxygen, abx. Advice to avoid alc, strenuous ex, stay warm, abx prophylaxis penicillin V
  Prophylactic treatment - hydroxycarbamide (stimulates HbF), blood transfusions, bm transplant curative
  Other - Flu jab annual, pneumococcal every 5 years, hep b if receiving as chronic sleep damage due to infarction causing increased susceptibility to infections
• Complications: pul htn, leg ulcers, priapism, ckd, stroke, aplastic crisis (parvovirus b19)
  AVN - vaso-occlusive crisis where blood cells clog in capillaries causing distal ischaemia causing swelling + fever
  Spleen sequestration crisis: rbc block flow in spleen so enlarges + pooling blood = severe anaemia + hypovolaemic shock where blood transfusions and fluid needed. Can lead to spleen infarction and hyposplenism inc risk to encapsulated bacteria (strep pneum, haem influ)
  Acute chest syndrome: vessels in lung clogged (sob, fever, pain, hypoxia, pul infiltrates) - analgesia, hydration, blood transfusions, abx, oxygen, ventilation
• Extra facts
  Common causes of death are stroke, infection (pneumonia, meningitis, sepsis) in children
  HbS allele is survival adv against plasmodium falciparum in carriers hence selective advantage to pass on this mutation in areas of high malaria such as africa

Question 2

Lymphoma:
- Definition
- Causes (3)
- Risk factors (3)
- Symptoms (6)
- Signs (2)
- DD (2)
- Investigations (5)
- Management
- Complications (5)
- Extra facts: staging

Answer 2

Lymphoma:

• Definition: malignancy of lymphocytes in the lymphatic system divided into Hodgkin’s (better prognosis) and non hodgkins
• Causes: infection, genetic factors, environmental
• Risk factors: epstein barr virus, immunosuppression/organ transplant, other cancers, HIV, fam history
• Symptoms: palpable mass, B systemic symptoms (weight loss, night sweats, fever), lethargy, anorexia
• Signs: non tender lymphadenopathy (cancerous cells proliferating inside nodes), mediastinal lymphadenopathy with cough/wheeze/SVC obstruction
• DD: reactive lymphadenopathy (recent infection or lymphadenitis where tender/fluctuant), leukaemia
• Investigations: bloods (FBC rules out infection, U+Es including LDH inc to rule out tumour lysis syndrome before treatment begins), USS, CXR, CT full body, lymph node biopsy for definitive diagnosis (if non hodgkins Reed Sternberg cells which are cancerous b lymphocytes with 2 nuclei)
• Management: if airway compromise high dose steroids and airway support. If SVCO stent veins. Then chemo/radio. Then lifelong follow up
• Complications: tumour lysis syndrome (rapid lysis of tumour cells causes large release hence hyperphosphataemia, hyperkalaemia, hypocalcaemia, hyperuricaemia leading to kidney damage deranging U+Es + inc LDH so hyperhydration and allopurinol and if very severe dialysis), neutropenia, alopecia, sub-fertility, infections, tissue fibrosis (from radiotherapy)
• Extra facts: Lugano classification
  Stage 1: disease in single group nodes or single organ
  2: in 2 or more groups of nodes or organs on same side of diaphgram
  3: on both sides
  4: diffuse involvement

Question 3

Acute lymphoblastic leukaemia:
- Definition
- Pathophysiology
- Risk factors (1)
- Symptoms (6)
- Signs (3)
- DD (3)
- Investigations (5)
- Management
- Complications (4)
- Extra facts

Answer 3

Acute lymphoblastic leukaemia:

• Definition: malig disorder of the stem cells in the bm. Most common paed cancer in 2-5yrs
• Pathophysiology: mutation of lymphoid precursor cells (which become wbcs) create an uncontrolled capacity for self renewal and developmental arrest so in bm leads to proliferation hence excessive production of immature wbc blast cells leading to drop in functional rbcs, wbcs + platelets
• Risk factors: downs, kleinfelters, radiation exposure
• Symptoms: lethargy/pale/sob/dizzy (anaemia due to bm failure), easy bruising/bleeding (thrombocytopenia due to bm failure), fevers/infections (leukopenia due to bm failure), bone pain (increased pressure in hyperplastic bm), weight loss, headache/seizures (CNS involvement or cytokine release or leucostasis (inc plasma viscosity due to high wcc), fever, testicular enlargement (tissue infiltration)
• Signs: pale, excessive bruising, lymphadenopathy, hepatosplenomegaly (due to infiltration by cancer cells)
• DD: non accidental injury, immune deficiency, reactive lymphadenopathy
• Investigations: bloods (fbc within 48 hours (pancytopenia OR anaemia + thrombocytopenia + lymphocytosis (due to blast cells in circulation)), blood film (blast cells), cxr (mediastinal mass?), bm aspirate/trephine to confirm diagnosis, LP
• Management: resus + hyperhydration if high wcc to stop hyperviscosity, steroids if mediastinal mass, abx if infection, UKALL 2011 protocol which is intravasc chemo/orally/intrathecally)/ blood products / prophylactic anti fungals. Maintenance treatment 2 years for F and 3 years M. Regular follow up for 5 years then yearly
• Complications: infertility, stunts growth, AVN, peripheral neuropathy, mucositis, neutropenic sepsis
• Extra facts: 90% survival. Prognosis determined by:
  Age 1-10 yrs better
  WCC>50 at presentation poor
  Female better prognosis
  CNS involvement poor

Question 4

Pancytopenia:
- Definition
- Causes (4)
- Symptoms (3)
- Investigations (3)
- Management
- Complications (2)

Answer 4

Pancytopenia:

• Definition: low rbc (anaemia) + low wbc (leukopenia) + low platelets (thrombocytopenia)
• Causes: bm infiltration (acute leukaemia/lymphoma, chemo/radio), genetic condition, vit b12/folate def, autoimmune conditions which attack bm, drug attacking blood cells (rifampicin), liver cirrhosis
• Symptoms: pale/tired/fatigue/sob/dizzy, high rates infection, petechiae/bleeding/heavy periods
• Investigations: bloods (fbc, clotting, u+es, g&s), blood culture, bm biopsy
• Management: blood transfusion, hsct, don’t give nsaids or contact sports, hand hygeine
• Complications: increased risk of infection + bleeding

Question 5

Acute myeloid leukaemia:
- Definition
- Pathophysiology
- Risk factors (3)
- DD (4)
- Symptoms (5)
- Signs (4)
- Investigations (4)
- Management
- Complications (6)
- Extra facts

Answer 5

Acute myeloid leukaemia:

• Definition: genetic mutations in myeloid sc
• Pathophysiology: myeloid scs (usually becomes mature rbcs/wbcs/platelets) get uncontrollable capacity for self renewal and development arrest creating immature blasts. Now there is less room for healthy cells causing infection, anaemia, bleeding due to bm failure. These blasts can also infiltrate other tissues. There’s also systemic effects where cytokines released by these cells increasing plasma viscosity (due to high WCC)
• Risk factors: Down’s, Li Fraumeni syndrome, affected sibling
• DD: ALL, iron def anaemia, immune thrombocytopenic purpura ITP, immunodeficiency
• Symptoms: pale / lethargic / sob (anaemia), fever / recurrent infections (neutropenia), petechiae (thrombocytopenia) , bone pain / testicular enlargement / hepatosplenomegaly (tissue / bm infiltration), fever / malaise / headache (cytokine release/leucostasis)
• Signs: pale (anaemia), bruising (thrombocytopenia), hepatosplenomegaly, lymphadenopathy
• Investigations: bloods (fbc (pancytopenia), blood film (blasts), cxr, bm aspirate + trephine definitive diagnosis (under light microscopy shows myeloblasts with Auer rod inclusions)
• Management: chemo - 2 cycles. 1 to induce remission + 2 reduce risk relapse. Can also give haematopoietic sc transplant, bm transplant if not working
• Complications: neutropenic sepsis, myelosuppression, N+V, mucositis, hair loss, reduced fertility (cyclophosphamide), cardiotoxicity (doxorubicin), tumour lysis syndrome
• Extra facts:
  66% 5 year survival. If low cytogenetic abnormalities at diagnosis better prospects
  Spreads to CNS, skin, gums
  AML diagnosed when 20% or more blasts which have morphologic + histochemical characteristics of FAB subtypes (M0-M7)

Acute vs chronic leukaemia: acute is impaired cell differentiation so get lots of malignant precursor cells where chronic is excess prolif of mature cells but cell diff unaffected

Question 6

Anaemia in children:
- Definition
- Causes (7)
- Symptoms (6)
- Signs (7)
- Investigations
- Management
- Complications (2)
- Extra facts - categorising anaemia

Answer 6

Anaemia in children:

• Definition: low level of hemoglobin in blood (a protein found in rbcs which carries oxygen
• Causes: iron deficiency due to diet, blood loss from menstruation, sickle cell, thalassemia, leukaemia, hered spherocytosis/eliptocytosis, helminth infection
• Symptoms: tired, sob, headaches, dizzy, palpitations, pica + hair loss (specific to iron deficiency)
• Signs: pale, conjunctival pallor, tachycardia, tachypnoea, koilonychia / angular chelitis / atrophic glossitis / brittle hair + nails (all iron def), jaundice (hemolytic), bone deformities (thalass)
• Investigations: bloods (fbc (hb + mcv), blood film, reticulocyte, ferritin (if <30 confirms anaemia, but if > doesn’t exclude as can be raised in infection/inflamm), b12/folate, bilirubin (raised in hemolysis)), direct coombs test (autoimmune hemolytic anaemia), hb electrophoresis
  High reticulocyte count = big production rbcs to replace lost ones due to hemolysis/ blood loss
• Management: underlying cause, iron supplements, blood transfusion
• Complications: poor growth/development, fatigue
• Extra facts: categorising anaemia

1. Microcytic anaemia = low MCV indicates small RBC
   TAILS: thalassemia, anaemia chronic disease, iron def anaemia, lead poisoning, sideroblastic anaemia
   Thalassemia is defects in a or b chains which can hemolyse and conseq get extramed haemopoesis which can cause bone changes, impaired growth and iron overload
2. Normocytic anaemia
   Acute blood loss, anaemia chronic disease, aplastic anaemia, hemolytic anaemia, hypothyroidism
3. Macrocytic anaemia -
   Can be either
   Megaloblastic anaemia (impaired DNA synthesis so grows instead of dividing due to vit def): b12/folate def
   Normoblastic: alc, reticulocytosis (hemolytic anaemia or blood loss), hypothyroid, liver disease, azathioprine

Question 7

Anaemia in infancy:
- Causes (5)

Answer 7

Anaemia in infancy:
- Causes:

1. Physiologic: normal dip 6-9 weeks as high hb levels at birth causes high oxy levels causing - fb so erythropoietin production suppressed
2. Prematurity: in first few weeks of life esp bc less time receiving iron in utero from mum, rbc creation can’t keep up with rapid growth in first few weeks, reduced erythropoietin levels, freq blood tests
3. Hemolysis (hemolytic disease of newborn, hered spherocytosis, G6PD def)
   Hemolytic disease newborn: rhesus d - mum has R+ ag baby so when born mum makes ab and sensitised. During 2nd preg mum ab crosses placenta into fetus and attach to fetus rbc leading to hemolysis hence anaemia and high bilirubin levels hence jaundice. A direct coombs test will be + = is a test to see if ab attached to rbcs. + if acquired conditions such as transfusion reaction/SLE, - if inherited conditions (spherocytosis, thal, scd, g6pd def)
4. Blood loss
5. Twin twin transfusion

Question 8

Hyposplenism:
- Definition
- Causes (5)
- Pathophysiology
- Investigations (3)
- Management

Answer 8

Hyposplenism:

• Definition: reduced or absent function of spleen
• Causes: coeliac disease, sickle cell, splenectomy (trauma/b thalassemia, hered spherocytosis), graves, congenital asplenia
• Pathophysiology: spleen major component of reticuloendothelial system and is needed for ab mediated phagocytosis of encapsulated organisms (strep pneum, neiss meningitidis, haemophil) hence can lead to systemic bacterial infection
• Investigations: splenomeg if scd, blood smear (howell jolly bodies (remnants if rbc nucleus typically removed by spleen), siderocytes (abnormal iron found in rbc)), uss to see spleen
• Management: immunisation with pneumococcal, meningococcal, haemophilus vaccines (if undergoing splenectomy give vaccines 14 days before, splenectomy not recommended if <4yrs bc risk of bacterial infection), prophylactic abx

Question 9

Disseminated intravascular coagulation DIC:
- Definition
- Pathophysiology
- Causes (4)
- Symptoms (3)
- Signs (4)
- Investigations
- Management
- Complications (3)

Answer 9

Disseminated intravascular coagulation DIC:

• Definition: dysregulated blood clotting
• Pathophysiology: intravascular activation of the coag cascade causes fibrin webs to form in small vessels and platelets to aggregate causing thrombosis. Also clotting factors used up in clotting pathway so inc risk of bleeding
• Causes: sepsis, complications during childbirth, malig, major trauma
• Symptoms: unusual bleeding (wounds/venepuncture sites/mucosal mems), widespread bruising, new onset confusion
• Signs: signs bleeding, petechia or purpura, livedo reticularis, signs of circ collapse
• Investigations: bloods (fbc (thrombocytopenia), clotting times (aptt, pt inc), D dimer (inc))
• Management: treat cause, platelet transfusion/ fresh frozen plasma if PT/APTT inc, heparin, cryoprecipitate if low fibrinogen
• Complications: kidney failure, multi organ failure, haemorrhage