Haem Flashcards
ITP
Ab against gp2b/3a, chronic in adults vs acute post-infection/ vacc in kids
= older F, petechiae, bleeding
Inv - FBC (v PLT), blood film
-> oral pred, IVIg (^PLT quicker)
Evans syndrome: AIHA + ITP
Transfusion: non-haemolytic febrile reaction
Ab reacting with white cell fragments, more likely in platelet transfusion
= fever, chills
-> slow / stop, paracetamol
Transfusion: minor allergic reaction
Foreign plasma proteins
= itchy, urticaria
-> temp stop, antihistamine
Transfusion: anaphylaxis
IgA deficiency patients who have anti IgA Ab
= hypotension, wheezing, SOB, angioedema
-> stop, IM adrenaline
Transfusion: acute haemolytic reaction
ABO incompatibility e.g., human error
= fever, abdo pain, hypotension
-> stop, fluids, check identity, direct Coombs/ type/ XM
Transfusion: TACO vs TRALI
TACO
Rate too fast, pre-existing HF
= pulmonary oedema, HYPERtension
-> slow or stop, IV loop, oxygen
TRALI
Host neutrophils activated by donor blood
= non-cardio pulm oedema, fever, HYPOtension
-> stop, oxygen
DIC
Normally coagulation and fibrinolysis are balanced, unregulated in DIC due to tissue factor release
Causes - sepsis, trauma, malignancy, obstetric issues
Inv - v platelets, v fibrinogen, ^ fibrinogen degradation products, ^PT / APTT, schistocytes (microangiopathic HA)
Iron Deficiency Anaemia
Causes - blood loss, diet (meat, green leafy veg), poor absorption, ^iron requirements
= fatigue, SOB on exertion, palpitations, pallor, spoon nails, hair loss, glossitis, angular stomatitis
Inv - FBC, v ferritin (correlates to iron stores but APR), v transferrin sat, ^TIBC, ^transferrin, film (diff sizes and shapes, pencils)
-> oral ferrous sulphate (for 3m after corrected), if no tolerated and need surgery then use IV iron
Hereditary Spherocytosis
AD, extravascular haemolytic anaemia, defect of cytoskeleton so destroyed by spleen
= FTT, jaundice, gallstones, splenomegaly, aplastic crisis (parvovirus)
Inv - ^reticulocytes, ^MCHC, film (sphere), EMA binding test
-> support or transfuse acute, longer term splenectomy and folate replacement
G6PD deficiency
X linked recessive, most common RBC defect, v glutathione so more prone to oxidative stress,
RF - Meditaranean/ African descent
Triggers - Fava beans, sulpha drugs, anti-malarials, ciprofloxacin
= neonatal Jaundice, gallstones, splenomegaly,
IV haemolysis, Heinz bodies, bite and blister cells.
Inv - diagnose with G6PD enzyme levels 3m after attack
Acute Intermittent Prophyria
AD, rare, issue in the biosynthesis of haem, leads to toxic accumulation of porphobilinogen and aminolaevulinic acid
RF - F, 20-40yrs
= abdo pain, vomiting, motor neuropathy, depression, HTN, ^HR, red urine on standing
-> avoid triggers, IV haem arginate (or IV glucose) for acute attacks
Antiphospholipid syndrome
Acquired disorder, can be 2nd to SLE
= arterial/ venous thrombi, recurrent fetal loss, thrombocytopenia, livedo reticularis, pre-eclampsia
Inv - paradoxical ^APTT, v PLT, anticardiolipin Ab
-> low dose aspirin for primary prevention, lifelong warfarin for 2nd prevention (target 2-3, 3-4 if more)
*In pregnancy + LMWH from when fetal heart beat is seen until 34 weeks
Aplastic Anaemia
Pancytopenia and hypoplastic bone marrow
Causes - idiopathic, may be presenting feature of AML/ ALL, Fanconi anaemia, parvovirus, hepatitis, chloramphenicol, phenytoin, sulpha, benzenes, radiation
= 30yrs, normo normo anaemia, leukopenia, thrombocytopenia
Autoimmune Haemolytic Anaemia
Causes - idio, 2nd to SLE, lymphoma, EBV, methyldopa
= anaemia, ^reticulocytes, ^LDH, ^BR, +ve Coombs, film (sphero, reticulo)
Warm
Most common, IgG causes haemolysis at room temp (extravascular)
-> steroids +/- rituximab
Cold
IgM causes haemolysis at 4 degree (intravascular)
Beta Thalassaemia
AR
Major (no beta globulin chains, chr 11)
= 1yr, FTT, hepatosplenomegaly, microcytic anaemia
^HbA2, ^HbF, no HbA
-> repeated transfusions, iron chelation to avoid overload
Trait
= no symptoms, mild hypochromic microcytic anaemia
^HbA2
Situation with CMV negative blood
Needed for:
- granulocyte transfusions
- intra uterine transfusions
- neonates <28 days post-expected delivery
- pregnancy
Irradiated Blood
Depleted of T cells to prevents GvH disease
Needed for:
- granulocyte transfusions
- intra uterine transfusions
- neonates <28 days post-expected delivery
- bone marrow/ stem cell transplant
- Hodgkin lymphonma
(NOT pregnancy and HIV)
FFP
Used for clinically significant but not major bleeds where PT / APTT >1.5
Also prophylaxis before risky surgery
Cryoprecipitate
Factor 8 , VwF, fibrinogen, factor 13 and fibronectin
Used for clinically significant but not major bleeds where fibrinogen (<1.5)
Prothrombin Complex Concentrate
Used for emergency reversal of AC in those with severe bleed or IC bleed
Burkitts Lymphoma
High-grade B cell cancer caused by c-myc t(8:14)
Endemic form (jaw, Africa, EBV) vs sporadic (abdo tumour, HIV)
Inv - microscopy (starry sky)
-> chemo, rasburicase (prevents tumour lysis, ^phos/K/uric, v Ca, renal failure)
AML
Most common acute leakamia in adults
Causes - primary or 2nd to myeloproliferative
= anaemia (pale, tired), neutropenia (frequent infections), thrombocytopenia (bleeds), splenomegaly, bone pain
Promyeloctyic M3
- Translocation 15:17, 25yrs, Auer rods, DIC, vPLT
CML
95% Philadelphia chromosome - BCR-ABL t(9:22)
= 65yrs, anaemia, weight loss, sweating, massive splenomegaly
Inv - ^granulocytes at diff maturations, thrombocytosis, v ALP
-> imatinib (TK inhibitor)
Comp - blast transformation (80% AML)
CLL
Monoclonal proliferation of B cells, most common adult leukaemia
= asymp, lymph, anorexia, weight loss, bleeding, recurrent infections
Inv - FBC (^WCC, v Hb, v PLT), film (smear cells: crushed little lymphocytes), immunophenotyping
Comp - warm AIHA, Richter’s (high grade NH lymphoma, suddenly unwell), hypogammaglobulinemia
Factor V Leiden
Most common inherited thrombophillia, activated protein C resistance
Factor V is inactivated much more slowly
= VTE
Fanconi Anaemia
AR
= aplastic anaemia, ^risk of AML, neuro issues, short stature, thumb/ radius abnormalities, cafe au lait spots
G vs H disease
Multi-system complication of bone marrow transplantation (also solid organs), poor prog
T cells in donor tissue mount an immune response against host cells
Acute (<100 days)
= painful maculopapular rash, TENS-like, jaundice, watery/ bloody diarrhoea, n+v, fever
Chronic (>100 days)
= scleroderma, viitiligo, lichen planus, keratoconjunctivitis sicca, corneal ulcer, scleritis, dysphagia, oral ulcers, ileus, lung disease
-> IV steroids
IV vs EV causes of haemolysis
In IV free haem binds to haptoglobin (-> saturated)
IV
- mismatched blood transfusion
- G6PD def
- Heart valves, TTP, DIC, HUS
- paroxysmal nocturnal haemoglobinuria
- Cold AIHA
EV
- Sickle cell, thalassemia
- Hereditary spherocytosis
- hemolytic disease of newborn
- Warm AIHA
Haemophilia
X linked recessive disorder of coagulation, A (factor 8) vs B (factor 9)
= bleeding into joints, prolonged bleeding
Inv - ^APTT but other tests normal (bleeding time, PT, thrombin time)
Hodgkin Lymphoma
Malignant proliferation of lymphocytes
RF - 20 and 75yrs, HIV, EBV, AI, FHx
= non tender asymmetrical nodes, pain on drinking alcohol (10%), weight loss, night sweats, itchy, fever
Inv - v Hb, ^eos, ^LDH, CXR (MS mass), node biopsy (Reed-Sternberg cells, multiple nuclei)
-> chemo
Hodgkin - types and staging
Subtypes
Nodular sclerosing - most common, good prog, F
Mixed - lots of RS cells, good prog
Lymphocyte predominant - best prognosis
Lymphocyte depleted - worst prognosis
Poor prognosis if; B symptoms, >45yrs, v Hb, v lymphocytes, v albumin, ^^WCC, male
Ann arbor
1 - single node
2 - 2 or more on same side diaphragm
2 - both sides of diaphragm
4 - past nodes
Hyposplenism
Causes - splenectomy, graves, sickle cell, coeliac, SLE, amyloid
Inv - Howell-jolly bodies, siderocytes
Lead poisoning
= abdo pain, peripheral neuropathy, neuropsychiatric features, fatigue, constipation, blue gums
Inv - blood lead level, FBC (microcytic anaemia), film (basophilic stippling, clover leaf)
Lymph drainage
Ovaries - Para-aortic lymphatics
Uterine fundus - para aortic and inguinal nodes
Uterine Body - iliac nodes
Cervix - external iliac, presacral and internal iliac
Causes of Normocytic Anaemia
Chronic disease
CKD
Aplastic
Haemolytic
Blood loss acutely
Causes of Macrocytic Anaemia
Megaloblastic - Vit b12 and folate lack
Normoblastic - alcohol, liver disease, hypothyroid, myelodysplasia and reticulocytosis
Multiple Myeloma
Haem cancer, plasma cell proliferation, large number of one type of antibody (Monoclonal paraprotein, IgG), ^70yrs
CRABBI
hyperCalcaemia (osteoclastic bone resorption, kidneys, ^PTH)
= constipation, nausea, anorexia, confusion
Renal (BJ light chain deposit in tubules, amyloid, calcinosis, stones)
= polydipsia, polyuria
Anaemia (v erythropoesis)
= fatigue, pallor
Bones (^osteoclasts, lytic lesions)
= back pain, fractures
Bleeding (marrow crowding)
= thrombocytopenia, hyperviscosity
Infection
Inv - FBC, blood film (rouleaux formation), U&Es, bone profile, protein electrophoresis (serum ^IgA/G, urine BJ light chain), bone marrow asp (^^plasma c), skull XR (rain drop)
*whole-body MRI 1st line
BLIP
MGUS
Monoclonal gammopathy of undetermined significance
Benign paraproteinaemia (mistaken for myeloma, 10% develop this)
= normal immune function, no lytic lesions or renal issues, no bone pain
Waldenstrom’s Macroglobulinaemia
Lymphoplasmacytoid malignancy, secretion of monoclonal IgM paraprotein
= older men, weight loss, lethargy, hyperviscosity syndrome (v vision), hepatosplenomegaly, nodes, cryoglobulinaemia (Raynaud)
-> chemo
Polycythaemia Vera
Myeloproliferative disorder
Clonal proliferation of marrow stem cell leading to inc red cell volume, 95% mutation in JAK2
= 60yrs, itchy after bath, splenomegaly, HTN, hypervisous (thrombosis), bleeds
Inv - ^HCT, ^neut/baso, ^PLT, ^ALP, v ESR, JAK2 mutation, ferritin, renal/ liver function
-> aspirin, venesection, chemo
Comp - 10% progress to myelofibrosis, 10% AML
Myleofibrosis
Myeloproliferative disorder
Hyperplasia of abnormal megakaryocytes leading to ^platelet derived growth factor, stimulates fibroblast formation, bone marrow replaced by scar tissue.
= old person, fatigue, massive splenomegaly
Inv - v Hb, ^WBC, ^PLT, film (tear drop poikilocytes), biopsy (dry tap), ^urate, ^LDH
Neutropenic sepsis
Complication 1-2 weeks post-chem, ^coag-neg gram +ve staph epidermidis (lines)
= neutrophils <0.5 + temp >38 or sepsis symptoms
-> immediate Abx (pip taz), may add meropenem at 48hrs, look for fungus at 4 days
Fluoroquinolone proph if risk
Paroxsymal Nocturnal Haemoglobinuria
Acquired disorder leading to haemolysis and ^VTE
- v GPI, activation of complement cascade, v CD59
= hemolytic anaemia, pancytopenia, dark urine in morning, prone to thrombosis
Inv - flow cytometry of CD59
Platelet transfusion cut offs
Active bleed:
<30 if clinically significant bleeding
<100 if severe bleeding or CNS
No bleeding and no better treatment:
<10
Prophylactic:
Aim for >50
50-75 if high risk of bleeding
>100 if surgery to critical site
Platelet transfusions carry the highest risk of bacterial contamination
Sickle cell
AR, formation of HbA, chr11 (same as b-thal)
Heterozygous trait = HbAS, v malaria risk
Homozygous disease = HbSS
Inv - Hb electrophoresis
-> 5 yearly pneum, hydroxyurea (^HbF, proph)
Crisis
-> opiate analgesia, rehydration, oxygen, blood transfusion
Sickle Cell Crisis
Thrombotic: sickled cells clog capillaries leading to distal ischaemia
Causes - infection, dehydration, high altitude
Inv - clinical diagnosis
Acute chest: vaso-occlusion in pulm vasculature
= SOB, chest pain
Inv - v pO2, CXR (pulm infiltrates)
-> pain relief, oxygen, transfuse, Abx if infective
Aplastic
Causes - parvovirus infection
= sudden fall in Hb, LOW reticulocytes
Sequestration: sickling in organs, pooling of blood
= worsening anaemia, ^reticulocytes
Thymoma
Most common tumour of ant mediastinum, 60yrs
Link - myasthenia gravis, dermatomyositis, SLE, red cell aplasia
Comp - cardiac tamponade, airway compression
Von Willebrand’s
AD, most common inherited bleeding disorder
Type 1 - partial reduction in VwF
Type 2 - abnormal form of VwF
Type 3 - total lack of it (AR)
= epistaxis, menorrhagia
Inv - ^bleeding time, mild ^APTT, v F8
-> tranexamic acid for mild bleeding, desmopressin (^ vWF), factor 8 conc
Tumour Lysis Syndrome
Breakdown of tumour cells leads to ^K, ^phosphate, ^uric acid, v Ca
-> IV fluids, IV allopurinol or rasburicase before chemo if high risk, allopurinol during chemo if lower risk
Clinical syndrome if electrolyte labs + any of;
serum creatinine 1.5x upper limit, cardiac arrhythmia, death, seizure
Tranexamic acid
Antifibrinolytic, reversibly binds to receptor sites on plasminogen or plasmin, can’t bind to fibrin
In trauma given as IV bolus then slow IV infusion
Superficial Thrombophlebitis
Inflammation of superficial veins, ^long saphenous
20% have an underlying DVT at presentation, 4% progress to one
Inv - US to excl. DVT if prox saphenous
-> NSAIDs (top if mild), top heparinoids, LMWH, compression stockings (ABPI first)
Smouldering Myeloma
Progression of MGUS with higher levels of the antibody, higher chance of becoming Myeloma
Pernicious Anaemia
Ab against parietal factor or IF causing B12 deficiency
Parietal cells produce intrinsic factor (enables B12 absorption in ileum)
-> IM Hydroxycobalamin (3x per week for 2wks, then 3 monthly)
**If low folate too, TREAT B12 FIRST (risk of subacute degeneration of the cord)
Post-thrombotic syndrome
Due to venous outflow obstruction and venous insufficiency
= painful heavy calves, itching, swelling, varicose veins and ulcers
-> compression stockings
Calcium disease Myeloma
The cytokines released by myeloma cells cause increased osteoclastic bone resorption.
This causes a high calcium with normal or high phosphate (the kidney disease in myeloma means it is not excreted). Normal ALP
INR Targets
AF - 2.5
VTE - 2.5
Recurrent VTE - 3.5
As a rule prosthetic mitral valves need higher INR then aortic
Anaemic of chronic disease vs iron def
TIBC in iron def - high
Low or normal in chronic disease
Varicose veins
Dilated tortuous superficial veins due to incompetent valves which allow backflow
= hyperpigmentation, hard tight skin, atrophie blanche (hypopigment), eczema
Inv - venous US
-> compression stockings
Surgical referral if:
Sig symptoms - swelling or pain
Bleeding
Skin changes
Thrombophlebitis
Active or healed venous leg ulcer
Non-Hodgkins Lymphoma
Most common lymphoma, B or T cell, high or low grade
RF - white, old, HIV
= later b symptoms, extra-nodal disease e.g., gastric, bone pain, nerve palsies
Inv - excisional node biopsy, CT TAP, HIV, ESR/ LDH for prognosis
-> wait, chemo (CHOP + rituximab), radio
Comp - marrow infiltration, SVC obstruction, mets, spinal cord comp
Red Cell Transfusion
without ACS vs with ACS
Transfusion threshold 70 g/L 80 g/L
Target after transfusion 70-90 g/L 80-100 g/L
Non-urgent scenario - unit over over 90-120 minutes
