Haematology Flashcards
Treatment for glandular fever?
- Supportive therapy (fluids, analgesia) - Avoid contact sports for 6 months eels to prevent splenic rupture
What does full blood count check for
RBCs - Neutrophils - Lymphocytes - - Platelets - Eosinophils - Monocytes
Abnormal FBC for neutrophils
High = neutrophilia, caused by acute bacterial infection Low = neutropenia, caused by myeloma and lymphoma
Abnormal FBC for lymphocytes
High = lymphocytosis, caused by chronic infection Low = lymphocytopenia
Abnormal FBC for platelets
High = thrombocytosis Low = thrombocytopenia
FBC values for eosinophils and monocytes
Eosinophils - elevated in parasitic infection - Monocytes - elevated in myelodysplastic syndrome
Ideal haemoglobin and mean corpuscular volume values
Haemoglobin: - Women: 120-165g/L - Men: 130-180g/L anything less than the lower value is classed as anaemia MCV: - 80-100 femtolitres
MCV for different types of anaemia
<80 = microcytic 80-95 = normocytic >95 = macrocytic
When would you consider transfusions for anaemia?
Hb <70g/L or Hb <80g/L + cardiac comorbidity
General symptoms of anaemia
Fatigue - Headache - Dizziness - Dyspnoea (especially on exertion) - Chest pain
General signs of anaemia
Tachycardia + hypotension - Skin pallor - Conjunctiva pallor - Intermittent claudication
Signs specific to iron deficiency anaemia
Koilonchia - Angular stomatitis - Atrophic glossitis - Brittle hair and nails - Subconjunctival pallor
Signs specific to thalassaemia
Bone deformities
Signs specific to B12 deficiency anaemia
Angular stomatitis + glossitis - Lemon-yellow Skin - Neurological symptoms
Signs specific to haemolytic anaemia
Prehepatic jaundice - Dark urine
Signs specific to CKD
Oedema - Hypertension - Excoriations on the Skin
Iron deficiency anaemia
Non-inherited Fe deficiency, impairing Hb synthesis - Most common anaemia worldwide - More common in females
Aetiology of iron deficiency anaemia
- Infants: malnutrition, prolonged breastfeeding - Children: malnutrition, malabsorption - Alults: malnutrition, malabsorption, menorrhagia, pregnancy, hookworm - Elderly (60+): rare, red flag for colon cancer bleeding
NICE recommendation for iron deficiency anaemia age 60+
Urgent endoscopy
What causes malabsorption of iron?
Conditions that result in inflammation of the duodenum and jejunum - Coeliac - IBD - Crohn’s disease Medications that reduce stomach acid (eg: PPI) - Because acid is needed to keep iron as the soluble Fe2+
Hookworm as a cause of iron deficiency anaemia
Most common cause worldwide - Results in GI blood loss
Normal iron function
Absorbed - Circulated bound to transferrin - Stored as ferritin or incorporated into Hb
Diagnosis of iron deficiency anaemia
FBC = microcytic - blood film - pencil cells (smol) platelet aggregates - Iron studies
What would a blood film of iron deficiency anaemia show?
- Small, hypochromic (pale) RBCs - Target cells - non-specific Bull’s eye pattern - Howell Jolly bodies - non-specific nucleated RBCs
Fe studies in iron deficiency anaemia
Serum Fe: Low - ferritin: Low - transferrin saturation: Low - Total Iron binding capacity (and transferrin): High
Treatment for iron deficiency anaemia
blood transfusion - immediate correction but need to treat underlying cause - Iron infusion - Oral Iron
Iron infusion
eg: cosmofer - Small risk of anaphylaxis - CI during sepsis
Oral iron
- Ferrous sulphate 200mg 3x a day - SE: constipation, black stools, GI upset - If poorly tolerated, consider ferrous gluconate - Unsuitable where malabsorption is the cause of the deficiency
What is thalassaemia?
Autosomal recessive haemoglobinopathy - A type of haemolytic anaemia - Defective alpha-globin chain = alpha thalassaemia - Defective beta-globin chain = beta thalassaemia
Pathophysiology of thalassaemia
- RBCs are more fragile and break down more easily - Spleen collect all the destroyed RBCs, resulting in splenomegaly - Bone marrow expands to produce extra RBCs -> susceptibility to fractures, pronounced forehead and molar eminence
Where is thalassaemia prevalent?
Where malaria is as it is protective from it (like sickle cell)
Alpha thalassaemia
- Less common - 4 gene deletions on chromosome 16 - Associated with HbH - Can cause death in utero if severe
Beta thalassaemia
- More common - 2 gene mutations in chromosome 2 - Normal Hb isoforms, just depletion of beta chains
Presentation of thalassaemia
Failure to thrive - Hepatospenomegaly - Gallstones - Chipmunk face
Diagnosis of thalassaemia
- FBC + blood film - Hb electrophoresis - diagnostic - Xr - “hair on end” skull
FBC and blood film in thalassaemia
hypochromic (pale) RBCs - Target cells - microcytic anaemia with High reticulocytes
Treatment for thalassaemia
- Regular transfusion - Iron chelation - Splenectomy - Ascorbic acid (vit C) - Bone marrow transplant (curative)
Iron chelation
Prevents Fe overload from transfusions - Desfemoxamine - SE: deafness, cataracts
Splenectomy
- Wait till after 6 y/o - Spleen plays defensive role vs encapsulated bacteria - So wait due to risk of sepsis
What is sideroblastic aneamia?
- Defective Hb synthesis within mitochondria - Often X inherited ALA synthetase deficiency - High Fe but not used in Hb synthesis, trapped in mitochondria!
Diagnosis of sideroblastic anaemia
FBC + blood film - Fe studies
Fe studies for sideroblastic anaemia
Serum Fe: High - ferritin: High - transferrin saturation: High - Total Iron binding capacity (and transferrin): Low
FBC and blood film for sideroblastic anaemia
microcytic - Ringed sideroblasts (immature RBC) - Basophilic stippling (increased Basophilic granules)
Haemolytic vs non-haemolytic anaemia
Failing bone marrow in non-haemolytic
Types of haemolysis
Intravascular - marked by haptoglobin - Extravascular - @ Spleen - Can be both
What is sickle cell anaemia?
Autosomal recessive haemoglobinopathy affecting beta-globin chains - Commonest in africa for antimalarial properties (vs plasmoduium falciparum) - HbS variant
Pathophysiology of sickle cell anaemia
- Glutamic acid -> valine on 6th codon of beta-globin on chromosome 11 - Causes irreversible RBC sickling - RBC more fragile so less efficient - Bone marrow focuses more on reticulocytes, decreasing other cell lines (eg: causes neutropaenia) - Intra+extravascular haemolysis
Presentation of sickle cell anaemia
General anaemia symptoms + prehepatic jaundice
What are sickle cell complications (crises) precipitated by?
Cold - Hypoxia - Acidosis - Dehydration - exertion - Stress
Types of sickle cell crises
Vaso-occlusive (aka painful crisis) - Splenic sequestration - Acute Chest syndrome - Aplastic crisis (from parvovirus) - Osteomyelitis
Another common complication of sickle cell anaemia
Osteomyelitis - Usually due to s.aureus, but in those patients = salmonella
Diagnosis of sickle cell anaemia
- Sickle solubility test- Newborn heel prick test - Antenatal: Molecular genetics - Hb electrophoresis - diagnostic when above 90% HbS (number 4 has sickle cell)
FBC and blood film in sickle cell anaemia
Normocytic normochromic - increased reticulocytes - Sickled RBC - Howell Jolly bodies
Last resort treatment for sickle cell anaemia
Bone marrow transplant
Long term treatment for sickle cell anaemia
Avoid precipitants - Drugs - hydroxycarbamide (aka hydroxyurea) to increase HbF levels, folic acid supplements - transfusion + Fe chelation
Vaso-occlusive crisis
Sicke shaped RBCs clog capillaries, causing distal ischaemia - Dehydration and raised haematocrit - Can cause priapism in men (treated with aspiration of blood from the penis)
Treatment for acute complicated attacks
Low threshold for hospital admission - treat any infection - Keep warm - IV fluids - Simple analgeisa
Splenic sequestration crisis
RBCs block blood flow within the Spleen - Can cause autosplenectomy - splenomegaly - Can lead to severe anaemia and circulatory collapse (hypovolaemic shock) - Splenectomy used in cases of recurrent crisis
Aplastic crisis
Temporary loss of the creation of new RBCs - Most commonly triggered by infection with parvovirus B19 - Management is Supportive with blood transfusions - Usually resolves spontaneously within A week
Acute chest syndrome sickle cell crisis
Caused by pulmonary vessel Vaso-occlusion - Fever or resp symptoms with new infiltrates seen on Xr - Can be due to infection or Non-infective causes - Medical emergency with High mortality
Treatment for acute chest syndrome
Exchange blood transfusion - sickle cell blood replaced w healthy blood
What is G6PDH deficiency
- X linked recessive enzymopathy - Causes 1/2 lifespan + RBC degeneration
What is G6PDH?
Glucose-6-phosphate dehydrogenase - Protects RBCs from vasoxidative damage - Involved in glutathione synthesis (Protects from ROS like H2O2)
Factors that can precipitate G6PDH deficiency
Naphthelene (in moth balls (pesticide)) - Antimalarials, eg: quinine - Aspirin - Fava beans (contain glucosides that Can be oxidised into ROS) - Nitrofurantoin
G6PDH attack
Rapid anaemia + jaundice (intravascular haemolysis)
Diagnosis of G6PDH deficiency
FBC + blood film - Normal inbetween attacks - Attack: normocytic, normochromic, increased reticulocytes, heinz bodies and bite cells Low G6PDH levels
Treatment for G6PDH deficiency
Avoid precipitants - blood transfusions when attacks ensue
What is hereditary spherocytosis?
Autosomal dominant membranopathy - common in Northern Europe and America
Pathophysiology of hereditary spherocytosis
deficiency in structural membrane protein spectrin - increased Splenic recycling (Extravascular haemolysis) - Makes RBCs More spherical and rigid
Presentation of hereditary spherocytosis
- General anaemia - Neonatal jaundice - Splenomegaly - Gall stones (50%)
Treatment for hereditory spherocytosis
Splenectomy
Treatment of neonatal jaundice in hereditory spherocytosis
treated with phototherapy - risk of kernicterus if untreated (bilirubin accumulates in basal ganglia, CNS dysfunction, death)
What is autoimmune haemolytic anaemia precipiated by
Precipitated by temperature (warm most common but idiopathic)
Pathophysiology of autoimmune haemolytic anaemia
IgM autoantibodies activate compliment system by binding to cell surface of RBCs - Intra/Extravascular haemolysis
Special test for autoimmune haemolytic anaemia
Direct coombs +ve - Agglutination of RBCs with coombs reagent
Diagnosis of hereditary spherocytosis
FBC and blood film: Normocytic, normochromic, spherocytes, increased reticulocytes - Direct coombs -ve - Eosin-5-maleimide (EMA) test - Cryohaemolysis
Myelophthisic process in non-haemolytic anaemia
Bone marrow replaced with something else (eg: malignancy)
Signs of G6PDH deficiency
Neonatal or Intermittent jaundice - anaemia - Gallstones - splenomegaly
Types of malaria
- Plasmodium falciparum (most severe and dangerous, 75% in the UK) - Plasmodium vivax - Plasmodium ovale - Plasmodium malariae
Pathophysiology of malaria
- Spread by female anopheles mosquitos - When mosquito bites human, sporozoites are injected - Travel to liver - Mature into merozoites which enter blood and infect RBCs - Merozoites replicate and RBCs rupture after 48 hours, cause a systemic infection
In what forms of malaria can sporozoites lie dormant in the liver for years?
P.vivax and P.ovale - Lie dormant as hypnozoites
Presentation of malaria
Blackwater Fever (malarial haemoglobinuria) - Massive hepatosplenomegaly - pallor - jaundice - Myalgia - Headache - Vomiting
Diagnosis of malaria
- Malaria blood film - 3 samples over 3 consecutive days
Oral treatments for malaria
quinine sulphate - Doxycycline
IV treatment for malaria
Artesunate (Most effective but not licensed) - quinine dihydrochloride
Complications of P.Falciparum
Cerebral malaria Reduced GCS AKI Seizures Haemolytic anaemia (severe) DIC Oedema Multi-organ failure and death
Antimalarials
- 90% effective at preventing infections Options: - Proguanil nad atovaquone (malarone) - Mefloquine - Doxycycline
Proguanil nad atovaquone (malarone) antimalarial
Most expensive - Best side effect profile
Mefloquinne antimalarial side effects
Bad dreams - Rarely psychotic disorders or seizures
Doxycycline antimalarial side effects
- Diarrhoea and thrush (as it’s a broad spectrum antibiotic) - Makes patients sensitive to the sun, causing a rash and sunburn
Pathophysiology of CKD anaemia
Occurs in chronic diseases - Decreased Bone marrow stimulation for production of erythropoetin
Diagnosis of CKD anaemia
Normocytic and normochromic - Decreased reticulocytes due to Low erythropoetin
Pathophysiology of aplastic anaemia
Pancytopenia where bone marrow fails and stops making haematopoetic stem cells
Cause of aplastic anaemia
Idiopathic - Could be infection (EBV, parovirus B19) or congenital
Diagnosis of aplastic anaemia
FBC = Normocytic anaemia with Decreased reticulocytes - Bone marrow biopsy = hypocellularity
Complication of aplastic anaemia
increased infection risk (neutropenia) - treat with broad spectrum antibiotic and Bone marrow transplant
Causes of B12 deficiency anaemia
- Pernicious anaemia (autoimmune, most common) - Gastrectomy - Malnutrition - Intestinal problems such as Crohn’s and celiac disease - Chronic nitrous oxide use - Oral contraceptives - Vegan (cool people basically😎)
Normal metabolism of B12
- B12 binds to transcobalamin 1 in saliva (protects against stomach acid) - Bind to intrinsic factor in duodenum - Absorbed as B12-IF complex in terminal ileum
Pathophysiology of pernicious anaemia
Anti parietal and intrinsic factor antibodies = Low if - Low B12-if complexes - Less B12 absorption
Neurological symptoms of B12 deficiency
Demyelination (DDx for folate deficiency) - Symmetrical parathesia - Muscle weakness - Altered mental state
What are haematinimics?
Nutrients needed for haematopoesis (B12, folate, Fe) - Deficiencies cause Angular stomatitis and glossitis
Diagnosis of B12 deficiency
FBC + blood film (Macrocytic and megaloblasts present) - Low Serum B12 - Anti parietal and Anti if antibodies (specific in Pernicious anaemia)
What are megaloblasts?
- Hypersegmented nucleated neutrophils with 6+ lobes - Less mature DNA = less compacted around histones - So more lobes = more immature
Treatment for B12 deficiency
Dietary advice - B12 supplements (PO hydroxycobalamin)
How long do folate and B12 deficiency anaemia take to develop?
folate: months - B12 : years (More common in older patients)
Aetiology of folate deficiency anaemia
malnutrition - malabsorption - pregnancy - Trimethoprim + methotrexate (dihydrofolate reductase inhibitors) - Alcohol - Bacterial overgrowth
Symptom of folate deficiency anaemia
Angular stomatitis
Diagnosis of folate deficiency anaemia
FBC + blood film = Macrocytic + megaloblasts - Low Serum folate - Could have concomitant B12 deficiency
Treatment for folate deficiency
Dietary advice (leafy greans, brown rice) - Don’t replace folate without checking B12 - folate supplements (if concomitant with B12 def., replace B12 first as giving folate first depleted B12)
Treatment for folate deficiency during pregnancy
- Prophylactic folate 400mg for first 12 weeks - Ensure baby develops ok
Main complication of folate deficiency
CKD
Causes of non-megaloblastic anaemia
Alcohol - toxic to RBC and depletes folate and B1 - Hypothyroidism - inteference w/ EPO, multifactorial - liver disease - liver decompensated cirrhosis - NAFLD - CKD
Pathophysiology of leukaemia
Neoplastic proliferation of WBC line (myeloblasts or lymphoblasts) - Lose ability to differentiate but maintain ability to replicate - Decreased production of other haematopoetic cells (functional pancytopaenia)
General signs of leukaemia
Thrombocytopaenia - bleeding and bruising - Leukopaenia - infections - anaemia symptoms - hepatosplenomegaly - Fatigue - Failure to thrive (Children)
Acute lymphoblastic anaemia (ALL)
- Neoplastic proliferation of lymphoblasts, mostly B - Terminal deoxynucleotidyl transferase expressed - Patients typically under 6 (75%) and over 50 - Associated with Down’s syndrome
Presentation of ALL
- General leukaemia symptoms - Lymphadenopathy - CNS infiltration -> headaches, CNS palsies
Testing for leukaemia
- FBC (shows pancytopaenia) - Blood film - Bone marrow biopsy - diagnostic - Imaging (CT/CxR) - Genetic testing
Blood films for leukaemia
- ALL - increased lymphoblasts - AML - increased lymphoblasts with auer rods, myeloperoxidase positive - CLL - smudge cells (Richter’s transformation)
Presentation of AML
General leukaemia symptoms - Gum hypertrophy
Acute myelogenous leukaemia (AML)
- Neoblastic proliferation of myeloblasts - Present mostly in the elderly (over 65) - Rapid progression if not treated asap - 3 year survival 20%, 5 year survival 15%
Leukaemia bone marrow biopsies
ALL - lymphoblasts ≥20% AML - myeloblasts ≥20% CLL - pancytopaenia (except lymphocytosis) CML - increased granulocytes, blast cell percentage shows severity (diff card)
Chromosomal translocations in leukaemia
ALL - mostly t(12:21) AML - t(15:17) CLL - multifactorial CML - t(9:22) (Philadelphia chromosome)
Philadelphia chromosome in ALL
- 30% in adults 3-5% in children - Worse prognosis
AML + DIC
common subtype of AML - Acute premyelocytic leukaemia (APML)
Chronic myelogenous leukaemia (CML)
- Neoplastic myelocyte proliferation - mainly neutrophils - Adults around 60 - BCR - ABL gene fusion causing tyrosine kinase to be irreversibly switched on
What do tyrosine kinases do
Increase cell proliferation
Chronic lymphocytic leukaemia (CLL)
- Neoplastic proliferation of lymphocytes, mostly B - Most common leukaemia in adults - Over 70 year olds, men typically - 5 year survival of 75%
Blast vs cyte
Blast - immature cell, eg: myeloblast Cyte - mature cell, eg: myelocyte
Presentation of CML
General leukaemia - Massive hepatosplenomegaly when with Malaria
Presentation of CLL
General anaemia symptoms - Often asymptomatic - Rubbery Non-tender Lymphadenopathy - Might have night sweats and weight loss
What is hypogammaglobulinaemia
- Low conc. of immunoglobulins present in CLL - This is because B cells proliferate but don’t differentiate to plasma cells (which are responsible for producing Igs)
Treatment of ALL
Chemotherapy - typically good prognosis
Treatment of AML
Chemo + tretinoin (used for APML) - transfusion for anemia - Abx prophylaxis for neutropaenia - Last resort: Bone marrow transplant
What to give with chemo
✨allopurinol✨ - Chemo releases uric acid from cells which can accumulate in kidneys - This would cause tumour lysis syndrome - Allopurinol prevents it
Treatment for CML
Chemo + imantinib (tyrosine kinase inhibitor)
Severity of CML based on blast cell % in bone marrow biopsy
- <10% - Chronic (best) 2. 10-19% - Accelerated 3. ≥20% - Blast crisis (worst, could progress to AML, poorer prognosis - often happens when CML is untreated or diagnosed late)
Treatment of CLL
Watch and Wait in early stages - Monoclonal antibodies (rituximab) - Bruton kinase inhibitors (ibrutinib)- Palliative (if v old) - IV Ig for hypogammaglobulinaemia
Complicaton of CLL
Richter transformations🥲 - B cells massively accumulate in lymph nodes - Mahoosive lymphadenopathy and transformation from CLL to aggressive lymphoma - #oops
What are B symptoms
Fever - night sweats - Unintentional weight loss
Ages susceptible to lymphomas
Hodgkin: Bimodal distribution, with peaks in early 20s and in 70s Non-Hodkin: Over the age of 40
Pathophysiology of Hodgkin lymphoma
Proliferation of lymphocytes in lymph nodes, typically in the cervical, axillary or inguinal lymph nodes
Risk factors of Hodgkin lymphoma
HIV - EBV (gladular Fever) - autoimmune conditions - Family history
Presentation of Hodgkin lymphoma?
B symptoms (Hodgkin is A High grade B cell lymphoma) - Non-tender Rubbery Lymphadenopathy which becomes painful after drinking Alcohol
Other possible symptoms of Hodgkin lymphoma
Fatigue - Itching - Cough - Dyspnoea - Abdo pain - recurrent infections
Diagnosis of lymphoma
Lymph node biopsy - PET-CT/MRI Chest/Abdo/pelvis for staging - Performance status score to establish treatment
How to distinguish between Hodgkin and non-Hodgkin lymphoma?
Lymph node biopsy (core needle/excision needle) - Hodgkin’s shows Reed-Sternberg cells🦉 - Abnormally large B cells with multiple nuclei and nucleoli - These aren’t present in Non-Hodgkin lymphoma, but you can still use the biopsy to determine NHL subtype, eg: Burkitt’s shows starry sky🌌
Popcorn cells🍿
- Seen in nodular lymphocyte predominant Hodgkin’s - (a subtype of Hodgkin lymphoma) - They are a variant of Reed-Sternberg cells
Ann Arbor staging in both types of lymphoma
- One region of lymph nodes 2. 2 or more lymph nodes on same side of the diaphragm 3. Lymph nodes on both sides of the diaphragm 4. Extranodal organ spread also: a - no B symptoms b - B symptoms
Treatment of Hodgkin lymphoma
- ABVD immunochemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) - +/- radiotherapy - Marrow transplant
Side effects of chemo for Hodgkin lymphoma
Alopecia - N+v - Myelosuppression - BM Failure - infection - Infertility - leukaemia
Side effects of radiotherapy for Hodgkin lymphoma treatment
Cancer - damage to tissues - Hypothyroidism
Types of Non-Hodgkin lymphoma
- Low grade - Follicular - High grade - Diffuse large B cells - Very high grade - Burkitt’s
Febrile neutropaenia
Massive risk in patients with recent/High dose Chemo (or on carbimazole) - Fever, Tachycardia, swears, rigors, tachypnoea - treated with immediate broad spectrum antibiotics
Cells affected in Non-Hodgkin lymphoma
- B cells (90%) - T cells (10%) - NK cells (<1%)
MALT lymphoma
Affects mucosal-associated lymphoid tissue - associated with H.pylori infection or eye chlamydia infection
Burkitt lymphoma
associated with EBV, Malaria and HIV - Often causes Massive jaw Lymphadenopathy in Children
Other risk factors for Non-Hodgkin lymphoma
- Hep B or C infection - Exposure to trichloroethyline (pesticide) - Immunosuppression
Presentation of Non-Hodgkin lymphoma
B symptoms - Non-tender Rubbery Lymphadenopathy, not affected by Alcohol - Can get hepatosplenomegaly
Treatment of low-grade lymphoma
- Radiotherapy - R-CHOP Chemotherapy Rituximab (targets CD20 on B-cells) Cyclophosphamide Hydroxy-daunorubicin Oncovin (brand name for vincristine) Prednisolone
Malaria in children
- Convulsions (60-80%) - High ICP, hypoglycaemia - Rule out meningitis (examination and CSF analysis if no high ICP)
Chronic complications of sickle cell anaemia
Avasular necrosis of joints - Silent CNS infarcts - Nephropathy - ED
Pathophysiology of multiple myeloma
- Neoplastic monoclonal proliferation of a plasma cell - Results in large quantities of a single type of antibody/monoclonal paraprotein being produced (55% IgG, 20% IgA)
Monoclonal gammopathy of undetermined significance (MGUS)
- Too much Ig released by abnormal plasma cells - <10% BM plasma cells - Asymptomatic - 1% of cases develop into myeloma
Smouldering myeloma
- Progression of MGUS with higher levels of antibodies - Premalignant, more likely to progress to myeloma than MGUS - Waldenstrom’s macroglobulinaemia is a type of smouldering myeloma with excessive IgM specifically
Epidemiology of myeloma
- Around 70 years old - Afro-Carribeans - Male - Obesity - 1% of cancers are myeloma
Presentation of multiple myeloma (🦀)
HyperCalcaemia Renal failure Anaemia Bone lesions
What are anaemia and bone lesions caused by in multiple myeloma?
Bone marrow failure
What are hypercalcaemia and bone lesions caused by in multiple myeloma?
Increased osteoclast bone resorption due to cytokines released by plasma and stromal cells
What is renal failure caused by in multiple myeloma?
- Hypercalcaemia -> calcium oxalase renal stones - Immunoglobulin light chain deposition - Bence Jones protein in pee
Testing for multiple myeloma
FBC and blood film - U+E = renal Failure - Bone profile = hypocalcaemia and increased ALP - Serum electrophoresis - urine dipstick - Bence Jones protein - Xr
FBC and blood film for multiple myeloma
Normocytic normochromic anaemia - raised ESR - Rouleaux formation in blood film (aggregation of RBCs)
Serum electrophorisis in multiple myeloma
- Ig paraprotein ‘M spike’ - Hypergammaglobulaemia for that specific Ig
X-ray for multiple myeloma
- Pepper pot skull - Osteolytic lesions -> “punched out holes”
Confirmatory diagnosis of multiple myeloma
- Bone marrow biopsy required - >10% plasma cells - NICE recommends full body MRI (if not, then CT or Xray in that order of preference)
Treatment of multiple myeloma
- Bisphosphonates (eg: alendronate) to decrease octeoclastic activit and increase osteoblastic activity - protects bones Older patients: - Anti-myeloma chemotherapy - Consider BM stem cell transplant
Plasma viscocity in multiple myeloma
- Increased due to large amounts of immunoglobulins in blood Complications: - Easy bruising and bleeding - Reduced or loss of sight due to vascular disease in the eye - Purple discolouration of extremities - Heart failure
Pathophysiology of polycythaemia vera
A High concentration of erythrocytes in the blood - due to JAK2V617 mutation - the affected Bone marrow Can also produce excessive Platelets and white blood cells
Relative vs absolute polycythaemia
Relative: - Normal number of erythrocytes, reduction in plasma - Causes include obesity, dehydration execessive alcohol and increased erythropoetin Absolute: - Increased number of erythrocytes - Primary and secondary
Primary vs secondary polycythaemia
Primary: Polycythaemia vera - abnormality in the bone marrow Secondary: Disease outside the bone marrow causing overstimulation of the bone marrow
General symptoms of polycythaemia
- Erythromalagia (fig 1) - Reddish plethoric complexion - Blurred vision - Headache + dizziness (features nonspeifically related to hyperviscosity)
Symptoms unique to polycythaemia vera
- Itchy after a bath (contact with warm water) 🛁 - Hepatosplenomegaly
Diagnosis of polycythaemia vera
FBC = High WCC, High Platelets, High RBCs - High Hb - Genetic tests JAK2V617 positive
Treatment of polycythaemia vera
Non-curative, main aim is to maintain a normal blood count Low-risk: - Venesection regularly (often used solely) - Low dose aspirin High risk: - Consider chemotherapy (hydroxycarbamide) for patients at high risk of thrombus (60+, background of thrombosis)
Thrombosis chart
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Differential diagnoses of abnormal or prolonged bleeding
Thrombocytopaenia (Low Platelets) - Haemophilia A and B - Von Willebrand disease - Disseminated Intravascular coagulation (secondary to sepsis)
Pathophysiology of ITP
autoimmune - antibodies (Usually IgG) created against platelet, causing platelet destruction - Specifically, Gpiib/iiia on Platelets are destroyed
Types of ITP
Type 1: Children 2-6, post viral infection, acute + severe Type 2: Adult women w malignancy, HIV or other autoimmune condition. Chronic + mild
Ge symptoms of thrombocytopaenia (all of the symptoms of ITP)
Purpuric rash - Easy bleeds - Mennhoragia Fig1. shows A Purpuric rash
Diagnosis of ITP
FBC - raised WCC, Low Hb, Low Platelets - increased Bone marrow megakaryocytes (due to negative feedback)
Treatment of ITP
First line: Prednisolone + IV IgG this decreases splenic platelet destruction Second line: Splenoctomy
Pathophysiology of TTP
- ADAMTS13 (VWF cleaving protein) deficiency - VWF remain as multimers and aggregate at endothelial injury sites - Incidence same as Type 2 ITP
Symptoms unique to TTP
AKI - Fever - haemolytic anaemia - Neurologicla symptoms
Diagnosis of TTP
- Same FBC as ITP - Raised billirubin and creatinine - Blood smear: schistocytes - RBCs; microangiopathic haemolytic anaemia - Genetic testing shows low ADAMTS13
Treatment of TTP
First line: Plasmapharesis Second line: Prednisolone + rituximab
What’s EBV associated with?
Many conditions inc: - Hodgkin’s lymphoma - Burkitt’s lymphoma - Nasopharyngeal carcinoma
Incidence and spread of EBV
- 15-24 years old - Spread via saliva or bodily fluids
Symptoms of EBV
Varied mild symptoms: - Fever - Tonsilitis - Hepatosplenomegaly - Cough Self limiting 2-4 weeks
Diagnosis of EBV
(Not with a green viral swab like most viruses) - FBC = Atyptical lymphocytes on blood film - Serology = EBV Igs with clotted sample - ELISA TEST
Types of HIV
HIV-1 - More common, Most virulent - HIV-2 - Less common, Less virulent
Transmission of HIV
Retrovirus - Sexual transmission - Sharing needles
Risk factors of HIV
Sharing needles, needle stick injury - MSM - unprotected anal sex
Pathophysiology of HIV
- HIB gp120 binds to CD4 on TH - Endocytoses RNA + enzymes - Reverse transcriptase RNA -> DNA - Integrase; viras DNA integrated into host’s - Protein synthesis - Viral proteins + RNA exocytose and take part of CD4+ cell CSM - Increased viral copies, decreased CD4+ (TH cells)
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- CD4+ dip then ‘set point’ 2. Clinical latency (years) 3. Symptoms 4. AIDS (CD4+ <200/mm3)
AIDS definining conditions
- CMV (eg: collitis -> owl eyes) - Pneomocystis jirovecci pneumonia - Kaposi sarcoma (fig1) - Cryptosporadium (fungal) infection - TB - Toxiplasmosis - Lymphomas
Diagnosis of HIV
history + Anti HIV Ig, P24 Ab (Elisa testing) - Monitor Progression - HIV RNA copies + CD4 count
Treatment for HIV
HAART - highly active antiretroviral therapy - 3 drugs <, reverse transciptase inhibitors - Aim is to maintain CD4 count and decrease HIV RNA copies
Epidemiology of haemophilia?
X linked recessive clotting factor deficiency so way more common in males
Types of haemophilia
A - Factor 8 deficiency, most common B - Factor 9 deficiency, also known as Christmas disease🎄 C - Factor 11 deficiency, very rare
Presentation of haemophilia
Spontaneous bleeds - Haemarthrosis (bleeding into joint) - V. Easy bruising - Epistaxis🤧
When do most cases of haemophilia present?
in neonates or early childhood - Intercranial haemorrhage, haematomas, cord bleeding
Diagnosis of haemophilia
Normal PT, long APTT (as only intrinsic pathway is affected) - Low CF assay (which factor depends on type)
Treatment for haemophilia A and B
A - high intensity IV factor 8 + desmopressin (releases F8 stored in vessel walls) every two days B - IV factor 9
Pathophysiology of Von Willebrand disease
- Autosomal dominant mutation of VWF gene on chromosome 12 - Defect in quality or quantity of VWF - VWF is responsible for the basis of the platelet plus -> more spontaneous bleeding and bruising - Most common inherited bleeding disorder
Presentation of Von Willebrand disease
Mucocutaneous bleeding: - Epistaxis - GI bleeds - Mennhoragia - Bleeding gums with brushing 🪥 - Heavy bleeding during surgery
Diagnosis of Von Willebrand disease
- Normal PT, long APTT - Normal factor 8/9 assay - Low VWF
Treatment of Von Willebrand disease
- Desmopressin (releases VWF from endothelial Weibel palade bodies) - IV factor 8 can also be infused for 2 weeks in severe cases - Tranexemic acid (antifibrinolytic)
Pathophysiology of DIC
- Tissue damage causes release and activation of tissue factor - Widespread activation of coagulation cascade and therefore platelet activation (crisis) - Platelets unnecessarily consumed + microthrombose in small blood vessels - Tissue plasminogen activator activated, leads to increased fibrinolysis - clotting removed - Lack of systemic platelets -> increased bleed risk
Aetiology of DIC
Trauma - sepsis (eg: meningococcal meningitis) - Malignancy
Diagnosis of DIC
Low Platelets - Low fibrinogen - increased D-dimer - long PT and APTT
Presentation of DIC
bleeding (epistaxis, bruising, rash, GI bleeding) - Acute resp distress syndrome
Treatment for DIC
treat underlying cause - Fresh frozen plasma to replace clotting factor - Cryoprecipitate to replace fibrinogen - platelet transfusion
Risk factors for G6PDH deficiency
X-linked recessive (men) - West African, Mediterranean, Asian
Heparin-induced thrombocytopenia
- Antibodies bind to heparin after administration -> prothrombotic state - Onset of emboli - Platelets <50%, D-dimer high - Treatment: stop heparin, anticoagulate
Pathophysiology of haemolytics uraemic syndrome
- Paediatric condition - Following infection with shiga-toxin producing bacteria like E.Coli/Shigella (typically 5 days after gastroenteritis) - Microvascular clot formation, deposition of platelets and fibrin in small vessels
Presentation of haemolytic uraemic syndrome
- Mostly self limiting but presents as medical emergency - AKI (oliguria, haematuria, hypertension) -> uraemia - Hameolytic anaemia - Thrombocytopaenia
Diagnosis of haemolytic uraemic syndrome
FBC - blood smear - differentiate from TTP with ADAMTS13 testing
FBC in haemolytic uraemic syndrome
Thrombocytopaenia - anaemia - High reticulocytes - High LDH - High bilirubin
Pathophysiology of tumour lysis syndrome
Collection of metabolic disturbances occuring with rapid destruction of Neoplastic cells Following Chemotherapy - More common in aggressive treatment of haem malignancies
Signs of tumour lysis syndrome
Hyperuricaemia, hyperkalaemia, hyperphosphataemia - hypocalcaemia - AKI
Types of haemostasis
Primary: Initiation and formation of platelet plug - platelet activation Secondary: Formation of the fibrin clot - coagulation cascade
PT/INR
- Work out INR using equation: Patient PT/Reference PT - Normal INR: 0.8 - 1.2 INR could be high due to: - Anticoagulants (eg: warfarin usually INR of 2-3) - Liver disease - Vit K deficiency - DIC
What is prothrombin time? (PT)
- Coagulation speed through extrinsic pathway - Normally 10-13.5s
What is activated partial thromboplastin time? (APTT)
- Coagulation speed through intrinsic pathway - Usually 35-45s - Patient on heparin may be 60-80
Other values measured for coagulation
- Bleeding time - Thrombin time - Fibrinogen -> fibrin time (usually 12-14s)
Treatment of haemolytic uraemic syndrome
Supportive fluids - antibiotics
Supportive treatment for multiple myeloma
Bisphosphonates - blood transfusion/EPO injection - antibiotics and pain-killers as needed - GCSF to boost Neutrophils - Radiotherapy - Kyphoplasty occasionslly indicated - Psychological support
What to give patients with sickle cell painful crisis?
IV fluids - Analagaesia - NSAIDs - Oxygen if Low - broad spectrum antibiotics due to neutropaenia
Two types of non-Hodgkin lymphomas
aggressive - quick onset but Can be treated - Indolent - worse prognosis
Indolent lymphoma
- Slow growing and advanced on presentation - “Incurable” - High on Ann Arbour scale - Median survival 9-12 years variable across and within subtypes
B symptoms of lymphomas
Fevers - night sweats - weight loss
Aetiology of indolent lymphoma
Primary and secondary immunodeficiency - infection - autoimmune disease
What are myelodysplastic syndromes?
Bone marrow cells fail to make adequate numbers of healthy blood cells - abnormal cells crowd out healthy Normal cells
What haematocrit is concerning in polycythaemia vera?
> 45%
Diagnostic pathway for thrombocytosis
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Diagnosis of thrombocytosis
- Ferritin 221, Serum iron 15, % iron saturation 23% - Blood film: Platelet anisocytosis (Platelets with size variation)- BCR::ABL1 no rearrangement on FISH - JAK2V617F mutated
Most common causes of splenomegaly
infection - liver disease - autoimmune conditions (eg: SLE, rheumatoid arthritis) Once excluded these: myeloproliferative neoplasms and lymphomas
What is bud chiari
Thrombus in hepatic artery - Increasing pressure - Leading to enlarged Spleen
What is multiple myeloma characterised by?
Monoclonal protein in Serum or urine - Lytic Bone lesions/ CRAB end organ damage - Excess plasma cells in Bone marrow
Reasons for decrease in RBCs
Decreased production - Iron, folate or B12 deficiency - Bone marrow failure Increased loss - Bleeding - Haemolysis
Causes of macrocytosis
folate or B12 deficiency - Reticulocytosis - raised Igs - Hypothyroidism - Alcohol - Bone marrow Failure, esp. myelodysplastic syndromes - Drugs, eg: methotrexate (inhibits folate metabolism), hydroxyurea
How much folate is needed daily?
0.1-0.2mg/day Isn’t stored
Where is folate absorbed?
In the proximal jejunum
Aetiology of AML
- Down’s syndrome - Radiation
Diagnosis of Hodgkin lymphoma
FBC: anaemia, High ESR - High LDH - CxR - Wide mediastinum - blood film - Reed Sternberg cells
Symptoms of G6PDH deficiency
Fatigue - Palpitations - Dyspnoea - pallor
Classic features of myeloma
Osteoporosis - Nephrotic syndrome - Hypercalcaemia - Thrombocytopaenia
What is the precursor condition to developing multiple myeloma?
Mammyloid gammopathy of undetermined significance
Symptoms of post thrombotic syndrome
Skin hyperpigmentation - Venous ulcers due to poor circulation in the leg - leg swelling
What percentage of patients with DVT get post-thrombotic syndrome?
30%
What to do if someone is at high risk for DVT
Ultrasound scan and give anticoags while waiting for results
What is antithrombin 3 deficiency
- Inherited (or aquired in nephrotic syndrome) - Antithrombin 3 inhibits factor Xa by binding to its co-factor heparin
HB structures
95% - HbA - 2x alpha - 2x beta 5% - HbA2 - 2x alpha - 2x delta Fetal - Fetal - 2x alpha - 2x gamma Sickle cell - 2x alpha - 2x HbS HbH - 4 x beta
What to give in suspected neutropaenic sepsis
One of the piperacillin (broad spec antibiotics) with tazobactam - Do blood cultures - IV fluids and Oxygen
Affects of warfarin and heparin on APTT and PT
heparin increases APTT - Warfarin increases PT
How does DIC cause infection
High clotting factors uses up platelets so systemic defences are down
What does ferritin increase in?
Infection - as it is an acute phase reactant
What conditions is autoimmune haemolytic anaemia secondary to?
leukaemia - lymphomas - SLE - any sort of infections (eg: EBV)
What is aplastic anaemia?
Pancytopaenia with hypocellular bone marrow
Signs of essential thrombocytosis
splenomegaly - Erythromelalgia (red or blue discolouration in peripheries with burning sensation) - Livedoreticularis
Risk factors for aquired haemophilia
Age >60 - IBD - Diabetes - pregnancy/ postnatal - Malignancy
Types of microcytic anaemia
Thalassaemia Anaemia of chronic disease Iron deficiency Lead poisoning Sideroblastic 🐒
