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🧫 Haematology
Name the causes of each of the following:
- 4 genes, they need at least one functional copy to be compatible with life
- Symptomatic when they have ≥ 2 copies
- Minor: Heterozygous
- Intermedia
- Major: Homozygous
- Failure to thrive in the first year of life
- Microcytic anaemia
- Prominent forehead
- Prominent cheek bones
- Marked poikilocytosis (speculated tear‐drop cells)
- Target cells
- Numerous erythroblasts
- Regular blood transfusions: Provide healthy, functional RBCs → Prevents intrinsic, dysfunctional erythropoiesis
- Iron chelation therapy (e.g. desferrioxamine) to prevent iron overload
See normocytic, can be microcytic or normocytic.
- Menorrhagia
- GI bleed
- Low dietary intake
- Malabsorption, e.g. Crohn's/Coeliac
- Shortness of breath
- Fatigue
- Palpitations
- Koilonychia
- Conjunctival pallor
- Angular stomatitis
- Oesophageal webs (Plummer-Vinson syndrome)
Investigations:
- Microcytic anaemia
- ↓ MCHC (Hypochromia)
- ↑ RDW (Anisocytosis)
- ↓ Ferritin (although this is an acute phase reactant so could be normal)
- ↑ Total iron binding capacity
- ↓ Transferrin saturation
Management:
Transfuse the patients if they have a Hb (but check local guidelines):
- ACS < 80 g/L
- Without ACS < 70 g/L
- Abdominal pain & neurological symptoms combined
- Blue lines on gum margins
- Inability to produce haem → Microcytic anaemia
- Intermittent porphyria
- Ineffective erythropoiesis → ↑ iron absorption & deposition in bone marrow, liver, heart & endocrine organs
- Congenital: Inherited in many different ways
- Drugs: Alcohol, lead poisoning, isoniazid
- Microcytic anaemia
- ↑ Ferritin
- ↑ Iron
- Pappenheimer bodies
Blood loss may cause anaemia (but may not initially), if the patient has sufficient iron stores to maintain normal red cell output then it will be normocytic.
- Chronic disease/inflammation → IL-6 release → ↑ hepcidin → ↓ Fe absorption
- Initially: Normocytic, normochromic
- Long-term: Microcytic, hypochromic
- ↓ TIBC
- ↑ Ferritin (acute phase reactant)
- ↑ RDW: Red cell distribution width will be increased due to a combination of both macrocytes and microcytes, that average out to be normocytic
- ↑ Ferritin: High because it is an acute phase reactant so stimulated by disease activity
Crohn's disease
- Micro: Fe deficiency due to blood loss from chronic bleeding.
- Macro: Low B12 absoption due to terminal ileum inflammation.
- ↓ Hb
- ↑ reticulocytes
- Idiopathic
- Congenital: Fanconi anaemia, dyskeratosis congenita
- Drugs: Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
- Infections: Parvovirus, hepatitis
- Radiation
- Leukaemia: ALL, AML
Types:
- Autosomal dominant inheritance
- Defect in the erythrocyte membrane → Breakdown by splenic macrophages
- Aplastic crisis in parvovirus infection
- Management: Splenectomy
- X-linked recessive
- ↓ G6PD → Oxidative RBC stress → Intravascular haemolysis
- Trigger: Patient ate fava beans, got an infection or started on antimalarial
- Result: Develop jaundice & anaemia following this
- Neonatal jaundice (High prevalence in African, Asian & Mediterranean people)
- Splenomegaly
- Heinz bodies (blood film)
- G6PD enzyme assay
- Sulph-drugs: Sulphonamides, sulphasalazine, sulfonylureas
- Ciprofloxacin
- Anti-malarials: primaquine
- Gender: G6PD only males
- Blood film: G6PD Heinz bodies
- Folate supplementation: ↑ RBC production
- Consider splenectomy
- Autosomal recessive
- Decreased water solubility of deoxy-Hb
- HbS polymerisation → RBC sickle
- Sickle cells are fragile → Haemolysis → Blocking of small blood vessels → Infarction
- 4-6 months → This is when foetal haemoglobin degrades and they rely on their own
- FBC - Microcytic anaemia, reticulocytosis
- LFT: Unconjugated hyperbilirubinaemia
- Blood film: Sickle cells, target cells, reticulocytes, Howell-Jolly bodies
- Haemoglobin electrophoresis +/- genetic testing
- Splenic infarction → Hyposplenism → Howell-Jolly bodies
- Priapism (painful, persistent erection) requiring aspiration of blood
- Severe anaemia
- Hypovolaemic shock
- Splenic infarction
- Fever/respiratory symptoms
- New infiltrates on CXR
- Infective: Pneumonia/bronchiolitis
- Non-infective: Pulmonary vaso-occlusion/fat emboli
- Failure of the bone marrow to produce any RBCs
- Parvovirus B19
This is rare, Hb drops due to increased haemolysis
- Avoid dehydration
- PenV prophylaxis
- Pneumococcal polysaccharide vaccine every 5 years
- Long-term hydroxyurea (stimulates HbF)
- Supportive
- Treat infection, keep warm, hydrated, analgesia
- Antibiotics if required
- Exchange transfusions
See microcytic anaemia.
- Direct coombs test
Two types:
- Extravascular: Spleen tags cells for phagocytosis
- CLL
- Lymphoma
- SLE
- Steroids: Immunosuppression is effective
- Intravascular: IgM causes complement to directly break down RBCs
- Mycoplasma
- EBV
- Lymphoma
- Cold agglutinins (IgM-complement complexes)
- ↓ serum haptoglobins
- Treat the underlying infection
- Immunosuppression is less effective compared with warm AIHA
Causes:
- Transfusion reactions
- Stop immediately & flush line
- Slow transfusion & give paracetamol
- Temporarily stop & antihistamine
- Mechanical (e.g. metallic heart valve)
- Microangiopathic haemolytic anaemia
- HUS: Haemolytic uraemic syndrome
- Triad: Microangiopathic haemolytic anaemia + thrombocytopenia + AKI
- Schistocytes on blood film
- DIC: Disseminated intravascular coagulation
- TTP: Thrombotic thrombocytopaenic purpura
- Paroxysmal nocturnal haematuria
- Complement system attacks the RBCs due to receptor mutation
- Haematuria in the morning
- Predisposed to thrombosis (DVT/PE)
- Smooth muscle dystonia
- Infectious: Malaria
- Plasmodium schizonts
- Hypersplenism (e.g. in liver cirrhosis)
Investigations:
- FBC
- Normocytic anaemia
- ↑ reticulocytes
- Blood film:
- Spherocytes
- Schistocytes
- Sickle cells
- LDH
- LFT: Bilirubin
- Serum haptoglobin
- ↓ in intravascular haemolysis (its role is to mop up excess Hb)
Gout
- Haemolysis → ↑ urate
See Endocrinology.
- Malabsorption
- ↓ dietary intake
- Crohn's
- Coeliac
- Pernicious anaemia
- Autoimmune parietal cell destruction → ↓ intrinsic factor → ↓ B12 absorption
- Intrinsic factor antibody
- Gastric parietal cell antibody
- Dietary IF replacement
- IM B12 injections, 3 monthly
- Hypersegmentation
- B12 concentration
- If B12 is low and you replace folate → Subacute combined degeneration of the cord
- Alcohol
- Liver dysfunction
- Pregnancy
- Reticulocytosis
- Intrinsic pathway: APTT
- Extrinsic: PT
- Tissue factor pathway inhibitor (TFPI): Forms complex with Xa which binds to VIIa:TF complex forming an inactive quaternary complex
- Anti-thrombin binds to Va/thrombin forming an inactive complex
- Heparin acts through this channel
- Protein C/S: Protein S activates protein C → Protein C inactivates Va & VIIIa
- Warfarin inhibits production of II, VII, IX, X
- Autosomal dominant
- Promotes platelet adhesion to damaged endothelium
- Stabilises factor VIII → Deficiency leads to VIII inactivity
- Partial reduction (80%)
- Abnormal vWF
- Complete lack of vWF (autosomal recessive) → Very severe
Platelet-pattern superficial bleeding:
- Easy bruising: Petechiae / purpurae
- Epistaxis
- Menorrhagia
- Normal PT
- Prolonged APTT
- Factor VIII decreased activity
- Prolonged bleeding time
- Only managed if the patient has been symptomatic:
- Tranexamic acid → Mild bleeding
- Desmopressin → Stimulates vWF release
- vWF & F.VIII infusion
- A: Factor VIII
- B: Factor IX
- X-linked recessive
Neonate/young child with severe large deep bleeds into soft tissue, joint & muscle:
- Haemarthrosis (bleeding into joints/muscles)
- Intracranial haemorrhage/haematoma
- Haematuria
- Serum factor VIII
- ↑ APTT
- ↔︎ Bleeding time
- Acutely for both: Tranexamic acid
Specifically:
- Haemophilia A: Cryoprecipitate (Factor VIII, fibrinogen, von Willebrand factor and factor XIII)
- Haemophilia B: IV infusion of factor IX (Replace the missing clotting factors)
There are two main causes:
- B12/folate deficiency
- Liver failure: ↓ Thrombopoietin
- Disorders affecting bone marrow production, e.g. leukaemia
- Disseminated intravascular coagulopathy (DIC)
- Coagulation cascade → Fibrin formation & polymerisation
- Fibrin formation → Plasmin formation → Clot breakdown
- Large insult (e.g. sepsis) → Excessive TF release → Formation of hundreds of small clots using up all platelets
- ↓ Platelets
- ↑ APTT
- ↑ PT
- ↑ Bleeding time
- Immune thrombocytopenia (ITP)
- Post-viral infection or vaccination
- Petechiae
- Bleeding (e.g. epistaxis)
- FBC: Isolated low platelets
- Conservative: Natural course 1-2 weeks
- Platelet transfusion if severe bleeding
- Thrombotic thrombocytopenic purpura (TTP)
- Focal neurology
- Haemolysis (Microangiopathic → Schistocytes)
- Thrombocytopenia
- Haemolytic uraemic syndrome (HUS)
- Bile duct occlusion → ↓ fat emulsion → ↓ absorption of fat soluble vitamins ADEK
- Red freckles on lips
- Recurrent epistaxis
- Other features: Brain, liver, lung bleeds
- Autosomal dominant
Arteriovenous malformations (AVMs)
- Arteries flow directly into veins rather than capillaries → High pressure blood flow in veins → Vein tears and irritation → Bleeding
- Defect in factors that normally inhibit the coagulation cascade → Excessive coagulation
Types:
- Antiphospholipid syndrome
- Persistent antiphospholipid antibodies associated with a variety of clinical features characterised by thromboses and pregnancy-related morbidity.
- History of systemic lupus erythematosus
- History of other autoimmune rheumatological disorders
- History of other autoimmune diseases
- History of autoimmune haematological disorders
- Lupus anticoagulant
- Anticardiolipin antibody
- Anti-β2-glycoprotein I
- LMWH initially before bridging to warfarin (or if pregnant remain on LMWH until after delivery)
- Lifelong warfarin:
- Target 2-3
- Target 3-4 (if VTE while on warfarin)
- Factor V Leiden (Most common hereditary)
- Factor V is resistant to deactivation by protein C → Overly active factor V → Increased coagulation
- Protein C/S deficiency
- Individuals from Southeast Asian heritage
- Protein C → Activated protein C → Breakdown of factor Va & VIIIa
- Antithrombin deficiency
Our main goals are management of acute thrombosis and prevention of thrombosis recurrence and pregnancy morbidity.
(via protein S)
- Well's score for DVT (2-level)
- ≥ 2
- Proximal leg doppler within 4 hours
- D-dimer if negative
- D-dimer
- Positive: Doppler within 4 hours
- If this isn't possible give LMWH
- Initial: LMWH
- Stop after 5 days or when the INR ≥ 2
- If using a DOAC, no heparin bridging is needed.
- Long-term: Warfarin/DOAC
- Provoked: 3 months
- Unprovoked: 6 months / lifelong
- Thrombophilia
- Antiphospholipid antibodies
ALL CeLLmates have CoMmon AMbitions:
- ALL < 5 years / > 45 years
- CLL > 55 years
- CML > 65 years
- AML > 75 years
- ↓ WCC (& neutropenic) → Infections
- ↓ Hb → Anaemia, lethargy, SOB
- ↓ Platelets → Bleeding
- Splenomegaly → Abdominal discomfort
- Bone pain
- Leukaemia
- Meningococcal septicaemia
- Vasculitis
- ITP
- HSP
- Non-accidental injury
- Acute: Blast cells
- Chronic: Mature cells
- Chemotherapy
- Risk of tumour lysis syndrome
- Steroids
Types:
- Children - Accounts for 80% of childhood leukaemia - Good prognosis
- Down's syndrome
- Adults (> 45 years) - Poor prognosis
- High WCC
- Lymphocytosis
- Adults (> 55y)
- Warm AIHA
- High-grade lymphoma (Richter's transformation)
- Smudge cells - Represent fragile WBCs
- > 75 years - Most common leukaemia in adults
- Auer rods
- Acute promyelotic leukaemia
- Presents in ~ 30 y/o with AML & DIC features
- Philadelphia chromosome [t(9;22) Bcr-Abl translocation]
- May have pseudo Pelger-Huet cells on blood film
- Massive splenomegaly
- Chronic (~ 5y): Often asymptomatic
- Accelerated: Blast cells take up 10-20% of blood
- Blast: > 30% of blast cells in blood → Pancytopenia & symptoms
- Acute leukaemia - AML (80%)
- Immunosuppression - Imatinib
Types:
Bimodal:
- ~ 20 years
- ~ 75 years
- Asymmetrical, painless lymphadenopathy
- Can be painful when drinking alcohol
- Night sweats
- Fever
- Weight loss
- Prurius - itching
- B-symptoms
- Lymphocyte depletion
- Age > 45 years
- Male
- High WCC
- EBV
- HIV
- High socioeconomic class
- Jewish ancestry
- Normocytic anaemia of chronic disease
- Eosinophilia
- Nodular sclerosing
- LDH (non-specific)
CT/MRI showing lymphadenopathy in:
- Stage 1: 1 area
- Stage 2: > 1 area, same side of diaphragm
- Stage 3: > 1 area, opposite sides of diaphragm
- Stage 4: Extra-nodal sites
- Reed-Sternberg cells (multiple nuclei) present in the centre
- Chemotherapy
- Radiotherapy
- Lymphadenopathy is usually widespread
- No Reed-Sternberg cells
- More common in adults
- Raised serum LDH
- B-symptoms
- Lymphadenopathy/organomegaly
- Anaemia
Types:
- Asymmetrical face swelling
- EBV
- C-myc
- 'Starry sky' appearance
- H. pylori chronic stomach inflammation → Mucosa associated lymphoid tissue
- Triple therapy to eradicate H. pylori
Most common lymphoma in U.K.
- Rapidly growing painless mass in > 65y
- Hepatitis C
- Calcium: Hypercalcaemia
- Renal failure: Antibodies block the tubule flow
- Anaemia: Bone marrow infiltration
- Bone pain/fractures: ↑ Osteoclast activity caused by cytokines released by plasma cells
- Bleeding: Thrombocytopenia
- Infection
- Urine Bence-Jones protein
- Serum-free Light-chain assay
- Serum Immunoglobulins
- Serum Protein electrophoresis
- Normal ALP (differentiates from bone metastases where ALP will be high)
- Normal phosphate
- Rouleaux: Stacks of aggregated RBCs
- Bone marrow aspirate & biopsy: > 10% plasma cells in bone marrow
- Punched out lytic lesions
- Raindrop skull
- Bisphosphonates: Zolendronic acid
- Suitable for transplant: Allogenic/autologous HPSC transplant
- Not suitable: MPT → Melphalan, prednisolone, thalidomide
- JAK-2
- PV: Hb > 185/165
- ET: Platelets > 600
- AML
Types:
- Cell line proliferation → Fibroblast stimulation → Bone marrow fibrosis → Pancytopenia
- Haematopoiesis can happen in liver & spleen causing enlargement
- 'Dry tap' because the bone marrow is filled with fibrosed tissue
- Poikilocytosis (varying sizes)
- Tear drop RBCs
- Pruritus (intense)
- Joint pain: Gouty arthritis
- Clots: Hyperviscosity of blood
- AML transformation
- Venesection
- Aspirin
- Dehydration: Pseudopolycythaemia (high RBC : plasma)
- COPD: ↓ SpO₂ → ↑ EPO → Polycythaemia
- Obstructive sleep apnoea
- Altitude
- Platelets are an acute phase reactant so are raised in stress e.g. infection/surgery
- Burning sensation in the hands
- Lung
- Reticulocytes → Haemolytic anaemia
- Spherocytes → AIHA, hereditary spherocytosis
- Heinz bodies → G6PD, ɑ-thalassaemia
- Auer rods → AML
- Smudge cells → CLL
- Howell-Jolly bodies → Hyposplenism/splenectomy, severe anaemia
- Target cells → Fe deficiency anaemia / splenectomy
- Schistocytes (fragmented RBCs) → HUS, DIC, TTP, metallic valves
- Anisocytosis (variation in RBC size) → Myelodysplastic syndrome
- Sideroblasts (immature RBCs containing Fe blobs) → Myelodysplastic syndrome
For the following blood films:
- Name the features seen on the film.
- Name the disease associated with these features.
- Target cells
- Thalassaemia/hyposplenism/sickle cell
- 'Tear drop' poikilocytes (poik - oddly shaped RBCs)
- Myelofibrosis - Large megakaryocytes stimulate fibroblasts
- Howell-Jolly bodies (remnants of the RBC nucleus, typically removed by the spleen)
- Hyposplenism
- Schistocytes
- Cold AIHA/mechanical heart valve/DIC (Any mechanical trauma)
- Acanthocytes
- Abetalipoproteinemia
- High grade lymphoma
- Leukaemia
- Combination chemotherapy
- Chemotherapy → Tumour cell breakdown → Release of cell contents into blood stream
- ↑ K⁺
- ↑ PO₄³⁻
- ↓ Ca²⁺
- ↑ Urea
- End organ damage:
- ↑ serum creatinine
- Cardiac arrhythmia
- Seizure
- IV allopurinol
Treat each individual electrolyte abnormality:
- IV rasburicase: Breaks down urea OR lactulose (longer acting)
- Treat other electrolyte abnormalities as normal
- Binds to plasmin → Plasmin can't break down fibrin clot
- Menorrhagia
- Trauma: IV bolus slowly infused
- Phenytoin
- Chloramphenicol
- Carbamazepine
- Quinine
- Immunological:
- Acute haemolytic
- Non-haemolytic febrile
- Allergic/anaphylaxis
- Infective
- Transfusion-related acute lung injury (TRALI)
- Transfusion-associated circulatory overload (TACO)
- Other: Hyperkalaemia, iron overload, clotting
- Urgent (major haemoorhage): STAT
- Non-urgent: 90 mins – 2 hours
- Haemorrhage < 100 x 10⁹
- Not unwell < 30 x 10⁹
- Prothrombin complex concentrate
- Fresh frozen plasma
- Cryoprecipitate
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