Haematology Flashcards
What is myeloma?
- Bone marrow cancer
- Cancer of differentiated B lymphocytes (plasma cells)
- leads to large quantities of single type of antibody being produced
- Multiple myeloma: affects multiple areas of body
What is the pathophysiology behind myeloma?
- genetic mutation causes uncontrolled multiplication
- Accumulation of malignant plasma cells leads to progressive bone marrow failure
- Mostly occurs in IgG
- Bence Jones protein found in urine of patients (antibody light chains)
What are the risk factors for myeloma?
- age
- male
- black african
- family history
- obesity
What are the 4 key features of myeloma?
- C: elevated calcium >2.75mmol/l (inc osteoclast activity)
- R: renal impairment: creatinine >1.73mmol/l
- A: anaemia
- B: lytic bone lesions
What is monoclonal gammopathy of undetermined significance (MGUS)?
- clonal antibody produced which doesn’t correlate to particular infection
- excess of a single type of antibody
- may progress to myeloma
What is smouldering myeloma?
- progression of MGUS
- premalignant
How is myeloma investigated?
- serum protein electrophoresis
- FBC and U&E
- urine electrophoresis (Bence-Jones proteins)
- X-ray for osteolytic lesions
What is the treatment for myeloma?
- Bisphosphonates
- thalidomide
- corticosteroids: dexamethasone - augments action of chemotherapies
What is sickle cell anaemia?
- single point 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?
- neoplastic, clonal proliferation of lymphoid cells
- Cancer of the white blood cells
- 2 categories: Hodgkin’s and non-Hodgkin’s (aggressive or indolent)
What is the aetiology of indolent lymphoma?
- Primary Immunodeficiency
- Secondary Immunodeficiency e.g. HIV; Recipients of Transplant
- Infection e.g. EBV; Helicobacter Pylori
- Autoimmune Disorders
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
- lactate dehydrogenase raised
- Reed-Stenberg test: abnormally large B cells with multiple nuclei: Hodgkin’s (owl eyes)
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
How is lymphoma treated?
- Hodgkin’s: DBVD: doxorubicin, bleomycin, vinblastine, dacarbazine
- NH: R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone
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 are the 3 Myeloproliferative Disorders and what is the definition?
- uncontrolled proliferation of a single stem cell type
- primary myelofibrosis
- polycythaemia vera
- essential thrombocythaemia
What is myelofibrosis?
- cytokines released from proliferating cells
- leads to proliferation of a cell line > fibrosis of bone marrow
- can cause anaemia and low WBC
- haematopoiesis occurs in liver and spleen > hepato and splenomegaly > portal hypertension
What type of cell line does primary myelofibrosis affect and what are the investigations?
- haematopoeitic
- investigations: anaemia, high/low wbc count, teardrop shaped RBC on blood film, varied rbc size, blast cells
How do Myeloproliferative Disorders present?
- systemic: fatigue, weight loss, night sweats, fever
- anaemia
- splenomegaly
- low wbc (infection)
- low platelets (bleeding, petechiae)
- portal hypertension (ascites, varices, abdominal pain)
- raised rbc (thrombosis, red face)
What is the cell line affected in polycythaemia vera and what are the investigations?
- erythroid
- raised Hb ( >16.5g/dL in men or >16g/dL in women)
What cell line is affected in primary thrombocythaemia and what are the investigations?
- megakaryocyte
- primary thrombocythaemia > 450*10^9/l
What are the 3 key signs of polycythaemia vera?
- conjunctival plethora
- ruddy complexion
- splenomegaly
How are Myeloproliferative Disorders investigated?
- bone marrow biopsy (aspiration > dry due to scar tissue)
- JAK2, MPL and CALR gene testing
How is primary myelofibrosis managed?
- Ruxolitinib
- erythropoietin injections
- analgesia for splenic discomfort
How is polycythaemia treated?
- aspirin 75mg daily
- venesection
- hydroxycarmabide 500mg daily
- aim to keep haemtocrit <0.45
How is thrombocytosis treated?
- aspirin 75mg daily: reduces blood clot development
- hydroxycarmabide 500mg daily
- aim to keep platelets 150-400
What is pernicious anaemia?
- 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 weekly depending on severity
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 aplastic anaemia?
- pancytopenia where the bone marrow fails
- deficiency in red cells, white cells and platelets
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
How is iron deficiency anaemia investigated?
- 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 transfusion
- iron infusion
- oral iron (ferrous sulphate)
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 investigations other than MCV, Hb and blood film can be done for haemolytic anaemia and what are the results?
- reticulocytes high (immature rbc)
- haptoglobin low (used up clearing fragments)
- LDH high (high cell turnover)
- bilirubin high
What are the complications of sickle cell anaemia?
- inc risk of infection
- avascular necrosis
- pulmonary hypertension
- CKD
- acute chest syndrome
How is sickle cell anaemia managed?
- antibiotic prophylaxis prevents against infection
- hydroxycarbamide stimulates production of 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?
- MC in Under 5 (and over 45) – acute lymphoblastic leukaemia
Over 55 – chronic lymphocytic leukaemia
Over 65 – chronic myeloid leukaemia
Over 75 – acute myeloid leukaemia
How does leukaemia present?
- fatigue
- fever
- failure to thrive (kids)
- lymphadenopathy
- abnormal bleeding/bruising
How is leukaemia diagnosed?
- FBC
- blood film
- LDH
- GOLD: bone marrow biopsy
How is leukaemia managed?
- chemotherapy and steroids
- radiotherapy
Describe acute lymphoblastic leukaemia
- malignant change in lymphocyte precursor cell
- acute proliferation of B-lymphocytes
- peaks in children 2-4yrs
- associated with Downs
- blood film shows blast cells
Describe chronic lymphocytic leukaemia
- chronic proliferation of well differentiated lymphocyte: usually B lymphocytes
- smear or smudge cells on blood film
Describe chronic myeloid leukaemia
- chronic, accelerated and blast phase
- chronic: 5yrs, raised white count
- accelerated: patients become more symptomatic and immunocompromised
- blast: even higher proportion of blast cells + blood
- associated with Philadelphia chromosome (t9:22)
Describe acute myeloid leukaemia
- can be transformation from myeloproliferative disorder or myelofibrosis
- 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
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 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)
- in adult women (malignancy, HIV, autoimmune)
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 IgG
What is thrombotic thryombcytopenic purpura and how does it present?
- inherited
- deficiency in enzyme clearing vWF so aggregation at endothelial injury sites
- symptoms: 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 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 autoimmune haemolytic anaemia?
- mediated by antibodies causing extravascular haemolysis and spherocytosis
- divided by optimal binding temp to RBC
What are the 2 types of autoimmune haemolytic anaemia and their treatments?
- Cold: IgG mediated - steroids
- Warm: IgM mediated, keep warm
What is tumour lysis syndrome?
- rapid cell death when starting chemo for rapidly proliferating blood cancers
- causes rise in urate, K, phosphate > renal failure
- 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
