Case 8: non malignant haematology basics Flashcards
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
