Case 8: non malignant haematology basics Flashcards
(49 cards)
1
Q
Top tips for coagulation tests
A
- Clinical bleeding history is more important then coagulation tests: tests dont reflect acute picture well
- Check is they are on anticoagulants
- Repeat test if unexpected
- Reference range differs between labs
2
Q
Intrinsic coagulation pathway
A
- factor XII, XI, IX, VIII. Count down from 12 then miss out 10
- ePartial thromboplastin time
- APTT is affected by issues in the common pathway and intrinsic pathway. If affects common PT will also be increased, if just intrinsic will be normal
3
Q
Extrinsic coagulation pathway
A
- Tissue factor is converted to factor X by factor VII
- Pro-thrombin time
- PT is affected by issues in the extrinsic pathway and common pathway. If affects the common pathway the APPT will also be prolonged, if only affects intrinsic will be normal
4
Q
Common pathway
A
- Factor X converts prothrombin to thrombin: releases factor V, Ca+ and lipids
- Prothrombin (II) is converted to thrombin
- Thrombin is converted to Fibrinogen (I) and then Fibrin clot (XII)
- The first four coins in our currency: 1, 2 ,5,10
5
Q
Causes of isolated prolonged PT
A
- Vitamin K deficiency: if mild to moderate increase, in early phases affects PT first
- Liver disease: in early stages on PT affected
- Warfarin (therapeutic range)
- Congenital FVII deficiency (rare)
- Acquired FVII inhibitors (very rare)
6
Q
Causes of isolated prolonged aptt
A
- Lupus anticoagulant: causes prolonged APTT but no increased bleeding risk. Can be transient or associated with SLE ant anti-phospholipid syndrome
- Unfractionated heparin: in therapeutic doses, can be with LMWH but less likely
- Congenital intrinsic factor deficiency: FVIII = Haemophilia A or FIX = Haemophilia B. If previous normal results the unlikely
- Acquired intrinsic factor inhibitors (rare): “Acquired haemophilia”- would be very prolonged
7
Q
Work up of isolated APTT
A
- Do a 50:50 mix of patients plasma and normal plasma (with normal coagulation facotors)
- Repeat APTT test
- If APTT corrects then suggests single factor deficiency i.e. Haemophilia A
- If APTT does not correct suggests: specific inhibitor (acquired haemophilia), non-specific inhibitor (lupus anticoagulant) or multiple factor deficiencies (DIC)
8
Q
Causes of prolonged PT and APTT
A
- Severe vitamin K deficiency
- Advanced liver disease
- DOACs
- Supratherapeutic warfarin therapy: really high INR
- Factor consumption (e.g. DIC)
- Congenital common pathway factor deficiency (very rare)
- Acquired inhibitors to common pathway factors (very rare)
9
Q
Tests to order for prolonged PT and APTT
A
- Thrombin time
- Liver enzymes, albumin, bilirubin
- Factor levels
- 50/50 mix
- Fibrinogen, D-dimers, fibrin degradation products (FDP)
- Antiphospholipid antibody testing
10
Q
Suggested factor screening
A
- FV represents the common pathway, is NOT vitamin K-dependent, and is only made by the liver
- FVII represents the extrinsic pathway, is vitamin K-dependent, and is only made by the liver
- FVIII represents the intrinsic pathway, is NOT vitamin K-dependent, and is made not only by the liver but also by endothelial cells. It is an acute phase reactant and can be elevated in disorders such as liver disease
INR: standardisation of PT between labs
11
Q
When to look for iron deficiency anaemia
A
- Anaemia – particularly microcytic (MCV low)
- Symptoms of iron deficiency
- At risk of iron deficiency/previous iron deficiency: heavy menstrual bleeding, recent blood loss
- Pre-surgery as a strategy to avoid transfusion: optimise prior to surgery
- Standard pregnancy management – booking (12w) and 28 weeks
12
Q
Symptoms of iron deficiency anaemia
A
- Symptoms of anaemia: SOB, chest pain, pallor
- Fatigue, poor concentration, low mood
- Hair thinning
- Itch
- Restless legs
- Koilonychia: spoon nails
- Glossitis
- Pica
13
Q
Causes of iron deficiency anaemia
A
- Inadequate dietary intake: veganism, vegetarianism
- Blood loss: blood donation or bleeding (ulcers, malignancy, gastritis, inflammation, parasites, menstrual)
- Malabsorption: coeliac
- Increased requirement i.e. pregnancy
14
Q
Investigations into iron deficiency anaemia
A
- Malabsorption: coeliac screen, H.pylori
- Urinalysis
- All men and post-menopausal women should be considered for endoscopy and colonoscopy, unless clear history of non-GI bleeding.
- FBC: Low Hb, MCV, MCH, RBC. RDW (red cell distribution) is normal or elevated. (If anaemic- can be iron deficient before becoming anaemic). Hypochromic microcytic anaemia
- Blood film (hypochromia (pale RBC, microcytosis, pencil cells). Anisopoikilocytosis, target cells, ‘pencil poikilocytes
- Ferritin: however is elevated with inflammation/liver disease so can be normal. If <15 is pathognomonic, <30 highly likely, 30-50 is borderline
15
Q
Tests for iron deficiency extra if unsure of diagnosis
A
- ron studies: Transferrin saturation less than 15-20 % suspicious for iron deficiency. Not very accurate as vary with time of day and dietary intake
- Reticulocyte haemoglobin – less than 28 pg = iron deficiency
- Total iron-binding capacity (TIBC)/transferrinwill be high. A high TIBC reflects low iron stores
- Percentage of hypochromic cells – more than 6 % = iron deficiency
- Zinc protoporphyrin – more than 80 = iron deficiency
- Trial of iron – oral iron increases by 20 g/L in three weeks
16
Q
Causes of low MCV
A
- TAILLS
- Iron deficiency
- Thalassaemia/haemoglobinopathy
- Anaemia of chronic disease
- Lead poisoning
- Inherited sideroblastic anaemia
17
Q
Treatment of iron deficiency anaemia
A
- Haem iron from meat/fish is better absorbed than non-haem iron: Once iron deficient then dietary changes are insufficient to correct: dark green leafy vegetables, meat, iron fortified bread
- Iron better absorbed prior to food and with vitamin C (e.g. fresh orange juice): Avoid antacids and tannins (tea, wine)
- Take in morning when hepcidin is lowest
- 100-200 mg elemental iron per day in divided doses
- Possible that 65 mg elemental iron alternate days is good enough
- Take for three months after normal haemoglobin. Aim for ferritin >50
- May need long term
18
Q
Parenteral iron
A
- More expensive, requires day unit etc.
- May work quicker – approx. 4-6 weeks haemoglobin at similar levels as before. Good if surgery is immenint
- Useful if: Inflammation, Dialysis, Not tolerated oral despite best practice, High levels of blood loss e.g. HHT, end stage renal failure and treated with Erythropoietin
- Very safe – rare reactions, low PO4, extravasation (brown stain on skin where blood leaked out)
19
Q
Hyperferritinaemia causes
A
- Raised ferritin: >300 ug/L in men, >200 ug/L in women
- Any inflammation including autoimmune disease, infections, malignancy
- Liver disease and metabolic syndrome
- Genetic haemochromatosis
- Renal failure
- Myelodysplasia
- Thalassaemia intermedia/major and other rare anaemias
- Chronic blood transfusion
- Porphyria cutanea tarda
- Other rare syndromes e.g. hereditary hyperferritinaemia cataract syndrome, Gaucher’s, acaeruloplasminaemia, Freidrich’s ataxia
20
Q
Tests for raised ferritin
A
- Check FBC, U&E, LFT, Inflammatory markers, Transferrin saturation
- FBC abnormal: consider iron loading anaemia, haemolysis, myelodysplasia, thalassaemia
- If Transferrin saturation high (>50% in men and >40% in women): consider genetic haemochromatosis and check HFE genotyping. High sats suggest iron overload
- Transferrin saturations normal: investigate for other causes i.e. inflammation, malignancy, liver disease, metabolic syndrome etc
21
Q
Microcytic anaemia
A
- Anaemia (Hb <130g/L in males or <120g/L in females)
- MCV <80 fL
22
Q
Genetic Haemochromatosis
A
- In UK 1 in 8 are carriers for HFE C282Y and 1 in 200 are homozygous. If carrier for HFE C282Y and HFE H63D then can also load iron
- Homozygous HFE C282Y leads to reduced hepcidin leading to increased ferroportin on bowel therefore increased iron absorption and increased iron release from macrophages
- No way to get rid of iron – leads to organ damage
- However less than 5% HFE C282Y homozygotes will get significant iron loading – depends on diet, other genetic modifiers, blood donation etc.
23
Q
Effects of iron loading secondary to Haemochromatosis
A
- Joint damage, osteoporosis
- Endocrine – diabetes, gonadal failure
- Bronzed skin
- Liver failure/cirrhosis, HCC
- Cardiac iron loading
- Patients with Hyperferritinaemia due to other causes tend to not get these complications
24
Q
Management of Haemochromatosis
A
- Check for complications; especially if ferritin over 1000 μg/L
- Check family (ferritin/transferrin saturation +/- HFE genotyping): no role for population screening due to variable phenotype
- Venesection – aim ferritin < 50 μg/L–Can become blood donor. Start with weekly then is only 3-4 times a year
- Diet – avoid iron and vitamin C, reduce alcohol
- Iron chelation if cannot do venesection
- Lowering ferritin does not improve cirrhosis or joint damage if already developed
25
Tests for Haemochromatosis
- Bloods: raised transferrin saturation, raised ferritin, low TIBC
- liver function tests
- molecular genetic testing for the C282Y and H63D mutations
- MRI is generally used to quantify liver and/or cardiac iron
- liver biopsy is now generally only used if suspected hepatic cirrhosis
26
MCV <80
- Iron deficiency
- Thalassemia
- Anaemia of inflammation
- Lead poisoning
- Sideroblastic
- Haemoglobinopathy: ie. Haemoglobin E, Haemoglobin SC, Haemoglobin
27
Investigations for MCV <80
- FBC, peripheral blood film, ferritin
- Haemoglobin electrophoresis
- Suspect β thalassaemia when Hb A2 >3.5%
- Normal Hb electrophoresis does not exclude α thalassaemia or iron deficiency
- In concomitant iron deficiency, Hb electrophoresis may be falsely normal; therefore, it should be repeated once iron stores are replete
- If α-thalassaemia suspected, order DNA testing
- If indicated, order serum lead level to rule out lead poisoning
28
Iron balance
- IN: RBC recycling, dietary iron content, intact epithelium (i.e. coeliac), intact epithelium (i.e. PPI)
- OUT: producing new RBC, pregnancy, lactation, gut desquamation, bleeding, menses, donation, intravascular haemolysis
29
Blood results in iron deficiency, chronic disease and thalassaemia trait
- Iron deficiency: MCV (low), Reticulocytes (low), Ferritin (decreased), Transferrin saturation (decreased), RBC count (low), RDW (high)
- Chronic disease: MCV (normal → low), Reticulocytes (low), Ferritin (increased), Transferrin saturation (decreased), RBC count (low), RDW (normal)
- Thalassaemia trait: MCV (very low <70), Reticulocytes (high), Ferritin (normal), Transferrin saturation (-), RBC count (high), RDW (normal/high)
30
MCV normal, low retic count
- Bone marrow failure: MDS, aplastic anaemia, congenital. Viral/toxic/septic BM suppression
- Bone marrow infiltration: lymphoma, leukaemia, myeloma, metastatic tumour, granulomatous disease
- Organ failure/endocrinopathy: liver disease, renal failure, adrenal insufficiency, chronic inflammation
31
MCV normal, high retic count
- Bleeding
- Haemolysis
- Treated nutritional deficiency
32
MCV >100
- B12/folate deficiency
- Liver disease
- Alcohol
- Drugs (methotrexate, sulfate, ART)
- Thyroid disease
33
Haemolytic anaemia
- Definition: increased rate of RBC destruction.
- Clinical features: pallor, jaundice, pigment gallstones, splenomegaly, sometimes
- Lab results: Reticulocytosis, elevated LDH, elevated indirect (unconjugated) bilirubin
34
Haemolytic anaemia: morphology
1. warm autoimmune haemolytic anaemia (WAIHA) – spherocytes
2. cold AIHA – agglutination
3. microangiopathic haemolytic anaemia (MAHA) – schistocytes, some spherocytes
4. Oxidative haemolysis – bite cells
35
Intravascular haemolysis
- Occurring in ABO incompatibility, G6PD, PNH, PCH, clostridial sepsis, mechanical valve, severe burns
- plasma free haemoglobin (hemoglobinemia)
- decreased haptoglobin (bound by free Hb)
- increased methaemoglobin (heme with Fe3+)
- haemoglobinuria and hemosiderinuria
- chronically, may lead to iron deficiency
36
Extravascular haemolysis
- Occurs in RES most causes of haemolytic anaemia
- Decreased haptoglobin
- Positive direct antiglobulin test (DAT or direct Coombs’) if immune-mediated
- No hemoglobinemia, methemealbunimenia, haemoglobinuria, hemosiderinuria
37
Extravascular haemolysis mechanism
- Intrinsic RBC defect- typically congenital: Membrane (hereditary spherocytosis, elliptocytosis), haemoglobin (sickle cell disease, thalassaemia), enzyme (G6PD, PK deficiency)
- Extrinsic Immune causes: warm autoimmune haemolysis, Cold autoimmune haemolysis, Paroxysmal cold haemoglobinuria
- Extrinsic non-immune mediated: RBC fragmentation syndrome, infections, toxin (snake venom, spider bites), chemical agents, Burns, drowning, march haemoglobinuria
38
Warm autoimmune haemolysis
- idiopathic vs. secondary
- Secondary causes include lymphoma, drugs, connective tissue disease
- IgG antibody, many different antigenic targets, including Rh antigens
- Primarily extravascular haemolysis
- Treatment: steroids, treat underlying cause
- Azathioprine, cyclophosphamide, etc for steroid-sparing
39
Cold autoimmune haemolysis
- idiopathic vs. secondary
- secondary causes include lymphoma (adults), infections (children; EBV, Mycoplasma pneumoniae)
- IgM antibody, antigenic target I or i
- Primarily intravascular haemolysis; degree of haemolysis determined by thermal amplitude of cold agglutinin, NOT titre.
- Treatment: steroids ineffective; supportive in children, treat underlying cause in adults. Cyclophosphamide (po or IV) can be used. Transfuse through a blood warmer.
40
Extrinsic causes of haemolysis: non immune mediated
- RBC fragmentation syndromes: Cardiac (valves, bypass, AVMs), MAHA – TTP/HUS, malignant HTN, DIC, HELPP, pre-eclampsia
- Infections
- Toxins (snake venoms, spider bites)
- Chemical agents: Copper (Wilson’s), Arsenic, Hypophosphatemia
- Burns, drowning, march haemoglobinuria
41
Lab results for blood tests
Lab results are only valid for the time at which they are taken. Low haemoglobin is the main indication for blood transfusion. Ranges differ from lab to lab and change in paediatrics.
42
Low haemoglobin
- Is there a haemorrhage- if not check size of red cells (MCV)
- Ferritin, B12, folate levels
- U&Es, LFTs, TFTs
- Blood film
- Reticulocyte count (and haemolysis screen): young RBC
- History: if HB has fallen slowly may be well tolerated at low levels. Rapidly falling Hb can make people feel ill even if only moderately low
- Check trend- has it always been low
43
Transfusion dependent patients
- Decision to transfuse is based on particular Hb threshold established by patient and caring team
- Behave different to ‘acute’ or ‘chronic’ anaemia
- Some benefit from transfusion others dont
- Sickle cell patients, Thalassaemia, bone marrow failure, myelodysplasia
44
Other triggers for red cell transfusions
- In stable patients without acute blood transfuse if: Hb < 70g/L in otherwise fit, Hb < 80g/L in elderly/cardiac/respiratory disease
- Critical care: A transfusion threshold of 70 g/L or below, with a target Hb range of 70–90 g/L – higher threshold in acute sepsis, neuro injury and acute coronary syndrome but should not exceed 90g/L
- Chronic anaemia: Consider alternatives and treat the cause. Maintain Hb just above lowest concentration associated with no symptoms. Only do if symptomatic with low count. Thalassaemia – Hb max 95g/L
- Post-chemo: Hb 80-90g/L threshold
- Radiotherapy: maintain Hb >100g/L
45
Dose of red cells in transfusion
- Depends on reason for transfusion
- Adults - in absence of blood loss, give one unit of red cells at a time and reassess response Hb and clinical symptoms (1u: 280-330ml)
- In low body weight adults (eg <50kg), consider weight-based volume transfusions (eg 4ml/kg)- be more cautious and tend not to give over 1 unit at a time
- Avoid over transfusion (unnecessary and risk of transfusion associated overload – TACO)
46
Blood transfusion epidemiology
Most people who get blood transfusion are >60, rates of blood transfusion is going down overall. Also peak in 0-4. Better to restrictively transfuse RBC then liberally. Important to consent patients for blood transfusions
47
Risks of blood transfusion
- Immunological: febrile, allergic (can be allergic against come donors), alloimmunisation (immunisation against babies blood), TRALI (rare). Can become immunised to some of the red cell antigens which can complicate a pregnancy be crossing the placenta and attacking some of the babies RBC
- Circulatory: Transfusion associated circulatory overload (TACO)- heart failure precipitated by a transfusion. Most common risk you see. Can occur with one unit, can be fatal
- Infection: bacterial, viral (HEV), vCJD. Quite rare blood is very safe
- Medical error: often due to several errors
48
TACO risk factors
- Already fluid loaded
- Known heart failure / other cardiac abnormalities
- Chronic lung disease
- Renal failure
- Significant hypoalbuminaemia
- Low body mass
- Elderly
49
Non-haemolytic febrile reactions
- Caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage
- Often due to sensitization by previous pregnancies or transfusions
- Features: fever, chills, often caused by platelet transfusion
- Management: slow or stop the transfusion, Paracetamol, monitor
