Haematology (paeds + GP) Flashcards
What is sickle cell anaemia?
- mutation in β global gene > HbS
- Autosomal recessive
- HbS polymerises when deoxygenated
- Blocks blood vessels > ischaemia, sequestration (away from organs)
- chronic haemolysis > low baseline Hb
How is sickle cell anaemia diagnosed?
- 1st line: sickle solubility test: cloudy looking
- Gold: HPLC, capillary electrophoresis (Hb separated based on size and charge)
What are some complications of sickle cell disease?
- sequestration in liver/spleen
- thrombosis (DVT, PE)
- acute chest syndrome
- aplastic crisis
- vaso-occlusive crisis
What is lymphoproliferative disease?
- Cancer of the white blood cells
- 2 categories: Hodgkin’s and non-Hodgkin’s (aggressive or indolent)
How does lymphoma present?
- lymphadenopathy > neck, armpit, groin
- non-tender, rubbery nodes
- b symptoms: fever, night sweats, weight loss
- pain after drinking alcohol (Hodgkin’s)
- recurrent infection
How is lymphoma investigated?
- lymph node biopsy: core needle or excision node
- raised LDH
- Reed-Stenberg test: abnormally large B cells with multiple nuclei: Hodgkin’s (owl eyes)
How is lymphoma treated?
- Hodgkin’s: DBVD: doxorubicin, bleomycin, vinblastine, dacarbazine
- NH: R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone
What is pernicious anaemia and the pathophysiology?
- B12 deficiency
- parietal cells produce intrinsic factor for B12 absorption in ileum
- antibodies form against parietal cells or intrinsic factor
How does pernicious anaemia present?
- peripheral neuropathy, paraesthesia
- loss of proprioception
- visual changes
- mood/cognitive changes
- lemon yellow skin
- angular chelitis and glossitis
How is pernicious anaemia diagnosed?
- testing for auto-antibodies
- 1st line: intrinsic factor antibody
- can also test for gastric parietal cell antibodies
How is pernicious anaemia treated?
- dietary: oral replacement with cyanocobalamin
- 1mg of IM hydroxycobalamin every other day/3x week for 2 weeks then 3 monthly
What is mean corpuscular volume (mcv) and what are the reference ranges?
- microcytic: <80
- normocytic: 80-95
- macrocytic: >95
- normal range: 120-165g/l in women or 130-180g/l in men
What are the causes of microcytic anaemia?
- T – Thalassaemia
- A – Anaemia of chronic disease
- I – Iron deficiency anaemia
- L – Lead poisoning
- S – Sideroblastic anaemia
What are the causes of normocytic anaemia?
- A – Acute blood loss
- A – Anaemia of Chronic Disease
- A – Aplastic Anaemia
- H – Haemolytic Anaemia
- H – Hypothyroidism
What is megaloblastic anaemia?
- megaloblastic: results from impaired DNA synthesis. Rather than dividing, the cell continues to grow becoming abnormally large.
- B12 deficiency
- folate deficiency
What are the causes of normoblastic macrocytic anaemia?
- hypothyroidism
- alcohol excess
- liver disease
What are the causes of iron deficiency anaemia?
- blood loss: menorrhagia, IBD, GI bleeding
- dietary insufficiency in children
- poor iron absorption
- increased requirements during pregnancy
How is iron absorbed in the GI tract?
- mainly absorbed in duodenum and jejunum
- stomach acid needed to keep iron in soluble Fe2+ form
- changes to Fe3+ when acid drops so PPIs interfere
- travels around the blood as Fe3+ bound to transferrin
What is seen on investigation of iron deficiency anaemia?
- low transferrin saturation and ferritin
- high total iron binding capacity: space for transferrin molecules to bind
- FBC
- blood film: Howell Jolly bodies
How is iron deficiency anaemia managed?
- OGD/colonoscopy if no clear cause
- blood/iron infusion
- oral iron (ferrous sulphate): take for 3 months after corrected for replenishment
How does iron deficiency anaemia present?
- koilonychia (spoon shaped nails)
- angular chelitis
- atrophic glossitis
- brittle hair and nails
What is thalassaemia?
- genetic defect in protein chains making up Hb
- autosomal recessive
- defects in α chains > α thalassaemia
- defects in β chains > β thalassaemia
What is the presentation of thalassaemia?
- fatigue
- pallor
- jaundice
- gallstones
- splenomegaly: RBC fragile so more damaged collected by spleen
- pronounced forehead and cheekbones: bone marrow expands
How is thalassaemia diagnosed?
- FBC
- Hb electrophoresis
- DNA testing
How is α thalassaemia managed?
- monitoring FBC
- blood transfusions
- splenectomy
- bone marrow transplant
How is β thalassaemia managed?
- monitoring
- transfusions
- iron chelation to prevent overload
What is haemolytic anaemia and how does it present?
- destruction of RBC leading to anaemia
- splenomegaly
- jaundice: bilirubin released during destruction
How is haemolytic anaemia investigated?
- FBC: normocytic anaemia
- blood film shows schistocytes (fragments)
- direct Coombs test: +ve in autoimmune haemolysis
What are the complications of sickle cell anaemia?
- infection
- avascular necrosis
- pulmonary hypertension
- CKD
- acute chest syndrome
How is sickle cell anaemia managed?
- Abx prophylaxis for infection
- hydroxycarbamide stimulates HbF
- blood transfusion
- bone marrow transplant
What are the different types of sickle cell crises?
- vaso-occlusive: sickle shaped cell clogs capillaries
- aplastic: temporary loss of creation of new RBC
- splenic sequestration: RBC block flow into spleen > splenomegaly > hypovolaemic shock
What is acute chest syndrome?
- results from sickle cell anaemia
- fever/resp symptoms + new infiltrates on X-Ray
- can be due to infection or emboli
- may need antibiotics, transfusion, ventilation
What is leukaemia?
- cancer of stem cells in bone marrow
- classified as acute or chronic
- myeloid or lymphoid depending on cell line affected
What is the pathophysiology behind leukaemia?
- genetic mutation in precursor cells leads to excessive production of single type of abnormal WBC
- leads to suppression of other cell lines
What is the epidemiology of leukaemia?
- ALL: 2-5 years
- AML: <2 years
How does leukaemia present?
- fatigue
- fever
- failure to thrive (kids)
- lymphadenopathy
- abnormal bleeding/bruising
How is leukaemia diagnosed?
- FBC
- blood film >20% blast cells
- LDH
- GOLD: bone marrow biopsy
How is leukaemia managed?
- chemotherapy and steroids
- radiotherapy
Describe acute lymphoblastic leukaemia
- acute proliferation of B-lymphocytes
- associated with Downs
- blood film shows blast cells
How does ALL present?
- anaemia: lethargy and pallor
- thrombocytopenia: easy bruising
- neutropenia: frequent infection
- bone pain
- hepato/splenomegaly
Describe acute myeloid leukaemia
- blood film: high proportion of blast cells
- may have Auer rods in cytoplasm
What is PT?
- prothrombin time: the time taken for blood to clot via the extrinsic pathway
- factor VII is the only factor in this pathway and rarely deficient so this measures overall clothing factor synthesis
- affected by liver disease, vit K deficiency, warfarin levels
What is INR?
- international normalised ratio
- calculated from PT: 1.0 represents the global average
- used to monitor patients on warfarin
- higher - takes longer to clot
What is APTT?
- activated partial thromboplastin time
- time taken for blood to clot via intrinsic pathway
- can indicate issues with factor VIII, vWF, IX and XI
- heparin can cause prolonged APTT
What is Ann Arbor staging for lymphoma?
- if affected nodes are above or below diaphragm
- Stage 1: confined to one region
- Stage 2: in more than one region on same side of diaphragm
- Stage 3: affects nodes above and below diaphragm
- Stage 4: widespread involvement inc non-lymphatic organs
What are some types of Non-Hodgkin’s lymphoma?
- Burkitt: associated w EBV, malaria, HIV
- MALT: affects mucosa-associated lymphoid tissue (H. pylori)
- Diffuse large B cell
What are risk factors for Non-Hodgkin’s lymphoma?
- HIV, EBV, malaria, H. pylori
- Hep B/C infection
- exposure to pesticides and trichloroethylene
- family history
What is von Willebrand’s disease?
- type 1: reduced amount of vWF
- type 2: defective vWF
- type 3: little/no vWF
- important in platelet adhesion and binds to factor VIII
- autosomal dominant
How does von Willebrand disease present?
- bleeding gums with brushing
- epistaxis (nose bleeds)
- menorrhagia
- heavy bleeding
- family history
How is von Willebrand disease investigated?
- APTT prolonged
- Low factor VIII
- immunoassay of vWF
How is von Willebrand disease managed?
- desmopressin: stimulates release of vWF
- infused vWF and factor VIII
- tranexamic acid
What is the presentation of haemophilia?
- spontaneous haemorrhage, bleeding into joints and muscles
- intracranial haemorrhage and cord bleeding in newborns
- bleeding: gums, GI, urinary tract, retroperitoneal space
How is haemophilia diagnosed?
- bleeding scores: prolonged APTT
- coagulation factor assays (factor VIII/IX)
- genetic testing
How is haemophilia managed?
- prophylaxis: infusions of factor VIII/IX
- avoid NSAIDs and contact sport
- desmopressin and tranexamic acid (antifibrinolytic)
What is haemophilia?
- X linked recessive inherited bleeding disorders
- almost exclusively affect males, women would need 2 affected X copies
- A: deficiency in factor VIII
- B: deficiency in factor IX
What are the normal reference ranges for neutrophils?
- neutrophilia: high - acute bacterial infection
- neutropenia: low - myeloma, lymphoma
What are the normal reference ranges for platelets?
- thrombocytosis: high - myeloproliferative disorders
- thrombopenia: low - 150x10^9 - ITP
What are the normal reference ranges for lymphocytes?
- lymphocytosis: high - leukaemia
- lymphocytopenia: low - infection
What is immune thrombocytopenic purpura (ITP) and who does it affect?
- autoimmune platelet destruction
- in children 2-6 (post viral infection)
How does ITP present, how is it diagnosed and how is it treated?
- symptoms: purpuric rash, easy bleeds
- diagnosis: thrombocytopenia, inc megakaryoblasts
- prednisolone and IV immunoglobulins
What is thrombotic thryombcytopenic purpura and how does it present?
- inherited
- deficiency in enzyme clearing vWF so aggregation at endothelial injury sites
- causes platelets to clump in vessels
How does TTP present?
- purpuric rash
- menorrhagia
- AKI
- anaemia
- neuro symptoms
How is TTP diagnosed and treated?
- diagnosis: thrombocytopenia, schistocytes, dec ADAMTS13
- treatment: plasmapheresis, prednisolone, rituximab
How does malaria present and how is it diagnosed and treated?
- anaemia, blackwater fever, hepatosplenomegaly
- blood film
- treatment: quinine and doxycycline
What is aplastic anaemia?
- pancytopenia where the bone marrow fails
- deficiency in red cells, white cells and platelets
What is sideroblastic anaemia?
- ineffective erythropoesis due to defective Hb synthesis
- leads to inc iron absorption, iron loading in bone marrow
- cardiac, endocrine and liver damage due to iron deposition
What is tumour lysis syndrome?
- rapid cell death when starting chemo for rapidly proliferating blood cancers
- causes rise in urate, K, PO4 > renal failure
- low calcium
- prevention with hydration and allopurinol
What is disseminated intravascular coagulopathy?
- widespread activation of coagulation due to release of procoagulant agents
- clotting factors and platelets consumed > inc risk of bleeding
What is hereditary spherocytosis?
- sphere shaped RBC
- easily destroyed
What is the epidemiology and inheritance of hereditary spherocytosis?
- MC inherited haemolytic anaemia in northern Europeans
- autosomal dominant
How does hereditary spherocytosis present?
- jaundice
- anaemia
- gallstones
- splenomegaly
- crises
What is aplastic crisis?
- increased anaemia, haemolysis and jaundice
- BM doesn’t create new reticulocytes
- triggered by parvovirus
How is hereditary spherocytosis diagnosed?
- family history and clinical
- spherocytes on film
- mean corpuscular haemoglobin conc is raised
- reticulocytes raised
How is hereditary spherocytosis managed?
- folate supplementation
- splenectomy
- transfusion in crises
