Haematology Flashcards
haemostats
is the cessation of bleeding, has three stages:
Vascular
Platelet
Coagulation
These occur in conjunction with each other as a result of multiple cascades
Haemostasis requires interaction of platelets, coagulation and fibrinolytic factors, endothelium,
Proinflammatory and anti-inflammatory mediators and leukocytes
Clot formation is initiated by vascular injury, in which a platelet plug forms and is reinforced
With fibrin produced via the extrinsic pathway
coagulation cascade
At the site of vessel injury platelets will arrive at the site to begin the clotting cascade
Involves extrinsic and intrinsic pathway
Extrinsic pathway:
Begins with now exposed molecules of the tissue wall such as tissue factor (contact system initiated)
Forms a complex with factor VIIa leading to activation of factor Xa
Point of Xa activation is point at which the extrinsic and intrinsic pathway meet
Intrinsic pathway:
Various coagulation factors such as IXa, XIa, XIIa which activate in cascade
An additional cofactor (VIIIa and IXa) combine with Xa to activate factor Xa (where pathways merge)
Combined pathway:
Xa is pivotal factor of clotting cascade
Xa combines with Va and Prothrombin further down cascade, catalysing prothrombin and inducing the ‘thrombin burst’
One Xa factor can catalyse 10,000 prothrombin to thrombin reactions
These large amounts of thrombin induce further platelet action and enhanced formation of fibrin
Fibrin forms strands which form the mesh that stabilises the clot during an arterial clot and holds the RBC together in a venous clot
Xa is a viable target for therapeutics involving pathological coagulation cascades
RBCs
7um diameter
No nucleus
Life span 100-120 days
Consists of 640 million molecules of hemoglobin (Hgb)
RBC count = total number of Hgb
Transports oxygen and CO2
Each Hgb transports four O2 molecules (oxyhaemoglobin) which carries to individual cells
Also binds to CO2 (carboxyhemoglobin), presence of CHgb helps release O2 from Hgb molecules
Haematological investigations for surgeries
Haematology is the study of blood components form and function and the coagulation system
Pre-operative care:
Assessment, diagnosis, management of safety issues
Preparation of patient centred care and decision making: pre op blood ordering, anaemia management, diabetes management, anticoagulation therapy management
Perioperative haem Ix:
Diagnostic assessment: diagnosis of blood diseases and abnormalities (e.g. patients general health)
Check for existing anaemias: bone marrow cancers, chemotherapy, vit B12/iron deficiencies, malabsorption disorders, liver disease, renal disease, anaemias, blood loss etc.
Prognostic assessment: identifies possibility of developing abnormal functioning blood, effective oxygenation and coagulation (e.g. how patients respond to their operations)
FBC
RBC: haemoglobin and haematocrit (in total)
WBC: differential count
Platelet count
Indications: Measures total Hgb or Hb in blood Indirect RBC measure Assessment of ongoing bleeding Evaluation of anaemic patients Normal range:
Male - 14-18 g/dl or 8.7-11.2 mmol/l
Female - 12-16g/dl or 7.4-9.9 mmol/l
Pregnancy - 11g/dl
Newborn - 14-24 g/dl
0-2 weeks - 12-20 g/dl
2-6 months - 10-17 g/dl
6 months - 6 years - 9.5-14 g/dl
6-18 years - 10-15.5g/dl
Elderly - Slightly decreased
indications of increased and decreased Hb
Indication of increased Hgb: Erythrocytosis Congenital heart disease Severe COPD Polycythaemia vera Severe dehydration
Indication of decreased Hgb: Anaemia Haemoglobinopathy Cirrhosis Haemolytic anaemia Haemorrhage Dietary deficiency Bone marrow failure Renal disease Normal pregnancy Rheumatoid/collagen vascular disease Haemolytic cancer Splenomegaly
RBC indices
Mean cell/corpuscular volume (MCV): average RBC size (80-100fL in adults)
Mean cell haemoglobin (MCH): average weight of RBCs (26-32 picogram)
Mean cell haemoglobin concentration (MCHC): average concentration of Hgb in RBCs (32-36g/dL)
haematocrit
volume % of RBC in whole blood.
Indication of Ix: Indirect measure of RBC no. and volume Rapid indirect measure of RBC count Serial assessment in ongoing bleeding Integral part of anaemic patient evaluation
Normal range:
Male - 42-52% or 0.42-0.52
Female - 0.37-0.47
Pregnancy - >0.33
Newborn - 0.44-0.64
2-8 weeks - 0.39-0.59
2-6 months - 0.35-0.50
6 months - 1 year - 0.29-0.43
1-6 years - 30-40%
6-18 years - 32-44%
Elderly - Slightly decreased
HCT/interfering factors:
Abnormality in RBC size
Haemodilution and dehydration
Unreliable levels immediately after haemorrhage
Extremely elevated WBC gives a decreased HCT (false anaemia)
Pregnancy shows decreased HCT
Chloramphenicol and penicillin both decrease levels
Living at high altitude increases HCT levels
WBC tests
evaluate infection, neoplasm, allergy and immunosuppression
- Total WCC
- Differential WBC count (different proportions of various WBC types)
Normal ranges:
Adults and children 2+ - 500-10,000/mm3 or 5-10 x10(9)/L
Children <2 - 6200-17,000/mm3
Newborn - 9000-30,000/mm3
neutrophils:
Phagocytosis of pathogens
55-70% normal
Lymphocytes
Natural killer cells, T and B lymphocytes
20-40% normally
B lymphocytes
Make Ig antibodies
T lymphocytes
Cooperate antibody production and attack infected cells
Monocytes
Phagocytosis
2-8% normally
Eosinophils
Phagocytose antigen-antibody complexes
1-4% normally
Basophils
Immune response to parasites and allergic reactions (hay fever)
0.5-1% normally
leukocytosis and leukopenia indications
Increased WBC indications (leukocytosis): Infection Neoplasia Malignancy Trauma, stress, haemorrhage, tissue necrosis Inflammation Dehydration Thyroid storm Steroid use
Decreased WBC indications (leukopenia): Drug toxicity Bone marrow failure Overwhelming infection Dietary deficiency (B12/iron) Bone marrow infiltration Autoimmune disease Hypersplenism (spleen extracts WBC aggressively)
coagulation screen tests
Platelet count (thrombocyte count PLT)
Clotting tests: prothrombin time (PT), fibrinogen, activated partial thromboplastin time (APTT), thrombin time and D’DIMER
APTT, PLT, PT and fibrinogen are standard coagulation tests prior to CV operations
Clotting screen normal range: Hb (g/dl) - Male: 13.5-18 or Female: 11.5-16 PT (s) - 12-13 aPTT (s) - 30-40 aPTT ratio - 1 (normal patient aPTT:present patient aPTT) INR - 1 Platelets (L) - 150-400 x10 (9) Fibrinogen (g/l) - 1.5-3
platelets
Forms in bone marrow
Small, round, non nucleated
Main role is maintenance of vascular integrity
Primary phase of hemostasis involves platelet aggregation
Platelet aggregation initiates the coagulation factor cascade
Normal values:
Premature infant - 100,000-300,000/mm3
Newborn - 150,000-300,000mm/3
Infant - 200,000-475,000/mm3
Child, Adult and elderly - 150,000-400,000/mm3
Greater than (thrombocytosis)
Less than (thrombocytopenia) Symptoms: easy bruising and frequent bleeding from gums, nost, GIT Caused by medications, congenital, leukaemia or lymphomas, chemotherapy, kidney infection/disease, excessive alcohol intake
fibrinogen
Normal range 60-100mg/dl or 1.5-4g/l
Derived from PT reaction as it occurs
Primarily a screen: any low fibrinogen detected is substituted for clauss fibrinogen test which measure fibrinogen directly
In disseminated intravascular coagulation the derived fibrinogen may be misleading
D’DIMER
Most notable subtype of fibrin degradation products
Levels of FDPs rise after any thrombotic event
Fibrin and fibrinogen degradation product (FDP) testing is commonly used to diagnose disseminated intravascular coagulation (DIC), PE, DVT, pregnancy, malignancy
During formation of a stable clot, amino acids are excised by various enzyme cascade reactions
The D’DIMER peptide is excised from the D portion of fibrin as the clot hardens
Therefore it is a useful predictor of recent clot formation
normal value:
for DIC in adult - 0.08-0.18 ugFEU/mL
for DVT/PE in adult - cut off for exclusion of VTE: <0.35ugFEU/mL
prothrombin time and INR
PT: time taken in seconds for blood to clot. Measures vitamin K dependent clotting pathways (extrinsic) therefore particularly measures warfarin activity (vit K antagonist)
PT and INR are calculations that monitor effectiveness of warfarin anticoagulation therapy
INR shows required dosage of warfarin to maintain balance between preventing clots and causing excessive bleeds for patients (aim for 2.5; between 2-3 in patients on warfarin)
Normal PT: 11-12.5 seconds
Full anticoagulant therapy: >1.5-2 x control value; 20-30%
Normal INR: 0.8-1.1
partial thromboplastin time PTT and thrombin time TT
Normal PTT: 60-70 seconds. Measures intrinsic clotting pathway, time taken for blood to clot. Useful in monitoring heparin therapy
Normal aPTT: 30-40 seconds. Provides ratio of APTT:normal clotting time and is primary calculator used to monitor heparin therapy
Thrombin time (TT):
Normal TT: 12-15 seconds. Measures time taken for fibrinogen to form fibrin (later clotting common pathway stage)
Primarily requested in liver disease units
operative haemorrhage and blood products
Primary bleeding: occurs within the intraoperative period. Resolved within operation. Major haemorrhages are recorded and patient monitored closely post operatively
Reactive bleeding: occurs within 24 hours of operation. Mainly from ligature slips or missed vessels (due to hypotension and vasoconstriction during operation). Once BP normalises post op this bleeding will occur
Secondary bleeding: occurs within 7-10 days post op. Due to erosion of a vessel from a spreading infection. Often seen when heavily contaminated wound is closed primarily
Blood products: Whole blood Packed RBCs Fresh frozen plasma (FFP) Platelet concentrates Cryoprecipitate
Thromboelastography TEG
Test of whole blood coagulation
Been shown to decreased usage of blood products and mortality during procedures (good for trauma)
May be used to screen patients for coagulopathy in blunt/penetrating trauma with hemorrhagic shock, those receiving massive transfusion protocol (1:1:1) to evaluate for discontinuation or guided product therapy or clinical suspicion for haemorrhage or coagulopathy
blood transfusion complications
Immunological complications Wrong blood episodes/errors Infections Immunomodulation Litigation
Early complications are rare but tend to be much more severe:
Acute haemolytic transfusion reaction: incompatible RBCs transfused. May lead to DIC. ABO incompatible transfusion has 10% mortality while non-ABO is less severe usually but can still cause intravascular hemolysis
Infective shock: bacterial contamination is rare but can be fatal. Acute onset hypotension, rigors and collapse rapidly following transfusion. Platelets more likely to be contaminated than RBCs
Transfusion related acute lung injury: acute respiratory distress due to donor plasma containing antibodies against patients’ leukocytes. <6 hours onset nonproductive cough, SoB, hypoxia and frothy sputum. May have fever and rigors. CXR shows multiple perihilar nodules with lower lung infiltration. Usually from multiparous women who have become alloimmunized
Fluid overload: too much fluid leading to pulmonary oedema, acute respiratory failure. Those at particular risk have chronic anaemia (normovolaemic/hypervolemic) or symptoms of cardiac failure prior to transfusion
Non-haemolytic febrile reaction to transfusion of platelets and RBCs: fevers and rigors can develop due to patients’ antibodies to transfused white cells. Multiparous women who have received multiple previous transfusions are most at risk. Not life threatening reaction, treat by slowing transfusion and paracetamol
Anaphylaxis: antibodies react to proteins in transfused blood components, release IgE or IgG antibodies. Urticaria and itching common within minutes of transfusion starting
haemoglobin
Protein in RBCs that carries O2 from the lungs to body tissues and returns CO2 from tissues to lungs
Made of four protein molecules (globulin chains) that are each connected and a heme (Fe containing porphyrin) totalling 8 components
Also plays role in maintaining the shape of the RBCs and helping maintain acid-base balance within circulation
blood
8% body weight
Blood is a connective tissue: made of living cells suspended in a non-living matrix (plasma)
Main function: transportation of oxygen, nutrients, hormones and signalling molecules
Whole blood contains: Red cells Platelets Plasma Cryoprecipitate (protein for blood clotting)
Centrifuge separates whole blood into three distinct layers:
Erythrocyte layer on bottom (red)
White cell and platelets layer in middle
Yellow plasma (55% blood volume) full of proteins, waste products, electrolytes and plasma proteins (albumin, alpha/beta globulins) mostly made in the liver
blood types
O, A, B, AB refers to type of antigen present (O = none present). Each type can also be Rh +ve or -ve making 8 types of blood
Each has a different glycoprotein in plasma membrane (antigen) that immune system can recognise
In different blood types, enter circulation will trigger an immune response due to unrecognised antigen present in the system.
Often targets foreign body with agglutination (sticking the cells together) which can cause clots
AB: universal recipients due to having both antigens so will recognise ALL blood types (O, A and B)
O: universal donor due to lack of antigens meaning it can be given to anyone of any blood type and not be detected by the immune system. However they are ONLY able to receive O type blood as immune system will detect and respond to both A and B antigens
Rhesus antigens: either have (+ve) or don’t (-ve)
Rhesus positive: can accept either +/-ve blood as they will recognise (do NOT have antibodies against) rhesus protein
Rhesus negative: stick to -ve donor blood as +ve will trigger immune response. Negative types can actually tolerate Rh+ve ONCE but after this they will develop antigens and lead to never accepting +ve blood again. This can be a problem in -ve mothers giving birth to +ve children if there is blood exchange. Is okay for one pregnancy but for any subsequent births she will need rhogam serum injection containing anti-rh antigens to block the mother’s immune response to her baby
erythropoietin cell cycle
Develop from committed stem cells to mature RBCs in about 7 days
Megakaryocyte erythroid progenitor (MEP), proerythroblast, early erythroblast, intermediate erythroblast, late erythroblast, nuclear erythroblast, nuclear extrusion, reticulocyte then RBC; each stage differentiates more by losing nuclei and proteins etc.
When matured in healthy individuals circulate for around 100-120 days (and 80-90 days in full term infant)
The regulation of formation is mostly from erythropoietin (EPO) from the kidneys (some in liver too) which is produced when hypoxia or low O2 levels are detected in the kidneys using hypoxia inducible factor (oxygen used to degrade/inactivate HIF so when hypoxic HIF signalling increases)
Old erythrocytes get more rigid and more likely to get stuck in capillaries. There are many channels to collect these older RBCs especially around the spleen (RBC graveyard) trapping old RBCs where macrophages engulf and digest components, separating them all into individual components for recycling or waste removal (amino acids, Fe stored in liver or put into new erythrocytes and haem turned into bilirubin for bile)
destruction process is called eryptosis
sickle cell anaemia
Autosomal recessive
Most common in african descent; must screen all african origin people for SCD pre-op
1/700 incidence
HbSS - homozygotes (SS) symptomatic sickle cell anaemia
HbAS - heterozygous - sickle cell trait (no symptoms but falciparum malaria resistant) may still experience symptomatic sickling hypoxia
SCD is most common in patients of africam indian, middle east and carribean descent as single copy of gene increases malarial resistance and is a selective advantage.
Pathology:
Foetal Hb (HbF) is usually replaced by HbA at around 6 weeks of age. Patients with SCD have an abnormal amount of variant Hb (HbS) which causes abnormal sickle shaped erythrocytes
Results from three interconnected sequelae of SCD
Vaso-occlusive crisis results in bone infarcts and subperiosteal haemorrhages
Chronic anaemia resulting in expansion of medullary spaces
Infection
These predispose individuals to complications such as growth disturbance and pathological fractures
Pathogenesis: Hypoxia Deoxygenated HbS Polymerises Deformity of RBCs, sickle cells cannot travel normally or carry oxygen Haemolysis + blocked small vessels
SCD investigations
Bloods: Hb 60-90g/L, reticulocytes 10-20%, high bilirubin. Haemolysis variable
Film: sickle cell and target cells
Sickle solubility test +ve but doesn’t distinguish between types
Hb electrophoresis confirms diagnosis
Pregnant women at risk of being carriers are offered testing during pregnancy
Newborn screening heel prick test at 5 days of age
XR: vaso-occlusive crisis can shoe osteonecrosis, subperiosteal and epidural haemorrhage, hand-foot syndrome (dactylics), growth disturbance, osteomyelitis or marrow hyperplasia in anaemia
SCD complications
Anaemia Increase infection risk Stroke Avascular necrosis in large joints Pulmonary HTN Painful and persistent penile erection (priapism) CKD Sickle cell crisis Acute chest syndrome
sickle cell crises
Umbrella term for spectrum of acute crises related to condition. Range from mild to life threatening, can occur spontaneously or triggered by stresses such as infection, dehydration, cold or significant life events.
There is no specific treatment for sickle cell crises and they are managed supportively:
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
Avoid NSAIDs (ibuprofen) in renal impairment
vaso-occlusive painful crisis (SCD)
Commonly occurs from microvascular occlusion causing distal ischaemia
Can be triggered by cold, dehydration, infection or hypoxia
Associated with dehydration and raised haematocrit
Symptoms typically include pain, fever, those of triggering infection
Bone marrow infarction causes severe skeletal pain; osteomyelitis presents with localised pain and systemic features of infection
Hands and feet show dactylitis (inflammation of finger or toes)
Mesenteric ischemia results in acute abdomen presentation
CNS infarction results in stroke, seizures, cognitive defects
Splenic infarction - susceptibility to infection (40% SCD childhood deaths)
Poor growth, chronic renal failure, gallstones, retinal disease, iron overload
Lung damage from hypoxia causing fibrosis and pulmonary HTN
Can cause priapism in men by trapping blood in penis causing painful and persistent erection (urological emergency treated with aspirin of blood from penis)
Management: no specific treatment are managed supportively
IV opiates, haematologist advice,
G+S bloods, FBC, reticulocyte count,
septic screen (Blood cultures, MSU + CXR),
Rehydrate (IV fluids) and keep warm,
NSAIDs and paracetamol analgesia
oxygen PRN,
consider empirical antibiotics if fever >38, unwell or chest signs
Penile aspiration if priapism (urological emergency)
splenic sequestration crisis (SCD)
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).
Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.
aplastic crisis and hand-foot syndrome (SCD)
Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
Hand foot syndrome:
Occurs in 50% children with SCD
Most common between 6 months and 6 YO
Usually have systemic symptoms of fever, elevated WCC
Characterised by swelling of hands and feet (uni or bilateral)
Usually self limiting
acute chest syndrome (SCD)
A diagnosis of acute chest syndrome requires:
Fever or respiratory symptoms with
New infiltrates seen on a chest xray
This can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause:
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
management of sickle cell
Cord blood taken at birth
Ensure vaccination up to date
Avoid dehydration and other triggers of sickle cell crisis
Pneumococcal prophylaxis (vaccine +/- penicillin V)
Hydroxycarbamide to stimulate HbF production which does not lead to sickling of RBCs (protective against sickle cell crisis and acute chest syndrome)
Blood transfusions for severe anaemia
Bone marrow transplant can be curative
Referral to hematologist for chronic management
Prevention: genetic counselling, parental tests and education can prevent 90% deaths form crisis
acute sickle cell crises protocol:
- analgesia
- haematologist early intervention
- septic screen: blood cultures, MSU, CXR
- rehydrate with IV fluids and keep warm
- oxygen PRN
- consider early empirical antibiotics if temperature, unwell or chest signs
aplastic anaemia
Condition where the body does not produce enough blood cells
Leaves the patient fatigued, prone to infection and uncontrolled bleeding
Rare and serious condition, can develop at any age, suddenly or gradually worsen over time, can be mild or severe
Can be short term or develop into chronic condition
Cause:
radio/chemotherapy
Exposure to toxic chemicals like pesticides, insecticides, benzene
Use of certain drugs (RA and some antibiotics)
Autoimmune disorders
Viral infection: hepatitis, epstein-barr, cytomegalovirus, parvovirus B19 and HIV
Pregnancy
Idiopathic
Associations:
Paroxysmal nocturnal hemoglobinuria: RBCs break down too soon which can lead to aplastic anaemia or vice versa
Fanconi’s anaemia (rare) inherited disease that leads to aplastic anaemia. Tend to have many birth defects
risk factors for aplastic anaemia and presentation
radio/chemotherapy Exposure to toxic chemicals Drugs Family history Pregnancy (rare)
Symptoms: Fatigue SOB Rapid irregular HR Pallor Frequent or prolonged infections Unexplained or easy bruising Nosebleeds or bleeding gums Prolonged clotting time Skin rashes Dizziness Headache Fevers
diagnosis of aplastic anaemia and management
Diagnosis:
Bloods: FBC (RBC, WCC, platelets all decreased)
Bone marrow biopsy (few blood cells present)
Management:
Depend on age and severity of condition
Anaemia caused by radio or chemotherapy may cease with treatment cessation
Pregnant women treated with blood transfusions and often improves once pregnancy ends
Severe is life threatening and needs immediate hospitalisation
Blood transfusion of RBC and platelets (complications can arise from multiple transfusions)
Stem cell transplant
Immunosuppressants (gengraf, noral, sandimmune), steroids (methylprednisolone)
Bone marrow stimulants: sargramostim, filgrastim, pegfilgrastim often used with immune suppressing drugs
Antibiotics and antivirals prophylaxis
coeliac disease
Multi Genetic disorder associated with HLA types DQ2 (90%) or DQ8, plus other genetic or environmental factors.
Family tendency 10-15%
Approx 1 in 100 people in the UK have coeliac disease, however only 10-20% will be diagnosed
Highest incidence in ages 50-69
coeliac disease presentation
wide variation of signs and symptoms, many cases are asymptomatic
Persistent unexplained abdominal or GI symptoms
Faltered growth
Unexpected weight loss
Severe or persistent mouth ulcers
Unexplained iron, vit B12 or folate deficiency
Type 1 diabetes
Autoimmune thyroid disease
IBS in adults
1st degree relatives of people with coeliac disease
Dermatitis herpetiformis (classic manifestations of CD)
Gluten sensitivity
NICE recommends serological testing for coeliac disease in people with the following:
Metabolic bone disorder
Unexplained neuro symptoms (ataxia, epilepsy, dementia, depression)
Unexplained subfertility or recurrent miscarriage
Persistently raised liver enzymes without known cause
Dental enamel defects
Down’s or Turner syndrome
All newly diagnosed type 1 diabetics are screened for coeliac disease*
coeliac disease investigations
only accurate if gluten diet is eaten during diagnostic process
Autoantibodies: total IgA and tTG 1st line. IgA EMAs if weakly positive.
For children: total TgA and IgA tTG 1st line. IgG EMA, IgG DGP or tTG if IgA is deficient
FBC: anaemia, iron and folate deficiency, B12, ferritin, LFTs (elevated transaminases which should return to normal on gluten free diet), Ca and albumin
Small bowel barium studies to exclude other causes of malabsorption
Biopsy needed for confirmation by GI endoscopy or suction capsule
coeliac disease referrals and management and complications
Referrals to GI specialist:
Young people with +ve serological tests for endoscopic biopsy
Children with +ve serology to paediatric specialist for further investigation
-Ve serology to gastro specialist if CD still suspected for further investigation
management:
Gluten free diet (no wheat, barely, rye, bread, cakes etc) seems to be only effective treatment
Refractory CD: consider prednisolone initial management while waiting specialist advice
If after GFD excluded but symptoms persist/serology is high for >12 months refer for endoscopic biopsy
Annual review to measure weight, height, review symptoms, assess diet and adherence, need for specialist dietitian or nutritional advice
Consider DEXA scan, regular bloods for long term complications monitoring
complications: Deficiencies eg vit D and iron Osteoporosis Cancer Ulcerative jejunitis Functional hyposplenism Anxiety, depression Male infertility Poor foetal outcome in UNDIAGNOSED pregnancy women, but not diagnosed
anaemias
Medical condition in which RBC count and/or Hgb is less than normal
Not a disease in itself instead may reflect underlying disease process and must be considered in relation to patients age and gender
Hb <13.5g/dl (adult male) or <11.5g/dl (adult female), varies in children based on age group
Aetiology:
Decrease in RBC production: iron & B12 deficiencies, aplastic anaemia, CKD (decreased erythropoiesis)
Increase in RBC destruction: sickle cell anaemia, G6PD deficiency, spherocytosis,
Increased RBC loss: bleeding (acute or chronic)
classification of anaemias
FBC: Hb level (men <13.0g/dl; female 11.5 g/dl; pregnancy - 11g/dl ((dilutional effect from increased circulating plasma making RBC % smaller in proportion)))
MCV (blood film): microcytic anaemia (MCV <80 femtolitres), normocytic (MCV 80-100 femtolitres), macrocytic anaemia (MCV >100 femtolitres); always look at these values when someone is presenting with anaemia (Low Hb); these values may vary based on labs so always look at reference ranges
Classification based on aetiology:
Nutrient deficiency or depletion (most common worldwide): iron Fe, folate def, B12 def.
Blood loss: acute (reticulocytosis (6hrs) causing normocytic anaemia) or chronic (ongoing iron loss causing microcytic anaemia)
Acquired bone marrow disease: aplastic anaemia (inherited bone marrow failure), autoimmune destruction of bone marrow cells
Chronic systemic disease: normocytic anaemia or in severe cases microcytic anaemia when coexisting with iron deficiency anaemia
Chronic kidney disease: main cause is decreased erythropoietin production leading to decrease RBC production causing norm/microcytic anaemia
Chronic liver disease: intravascular dilution leading to macrocytic anaemia
Autoimmune haemolytic anaemia: RBCs attacked by autoantibodies causing destruction (SLE, RA or scleroderma)
Genetic disorders (haemoglobinopathies): thalassaemias: group of autosomal recessive conditions resulting in decreased/absent alpha globin (alpha thalassaemia) or beta globin chains in the Hb molecule. Leads to RBC destruction and hemolytic anaemia. Sickle cell: haemolytic anaemia.
causes of microcytic anaemia
TAILS Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Sideroblastic anaemia
causes of normocytic anaemia
3As 2Hs: Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
causes of macrocytic anaemia
(deficiencies)
B12 deficiency
Folate deficiency
Normoblastic macrocytic: DARHL Drugs such as azathioprine Alcohol Reticulocytosis (usually from haemolytic anaemia or blood loss) Hypothyroidism Liver disease
anaemia presentation
Very nonspecific pallor/jaundice Fatigue Dyspnea Palpitations Anorexia Headaches Features of underlying disease Pica: dietary craving for inedible things like clay, dirt etc. Hair loss - iron deficiency anaemia
Signs:
Koilonychia is spoon shaped nails and can indicate iron deficiency
Angular chelitis can indicate iron deficiency
Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency
Brittle hair and nails can indicate iron deficiency
Jaundice occurs in haemolytic anaemia
Bone deformities occur in thalassaemia
Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease
anaemia investigations
Hb level
Blood film: MCV, MCH, MCHC
Haematocrit (Hct) aka packed cell volume (PCV): measures proportion of blood:other cells
Haemoglobin electrophoresis: screen test to identify normal and abnormal Hb and assess quantity
Coeliac serology: presence of anti-endomysial antibody or tissue transglutaminase antibody for patient with iron deficiency anaemia (IDA)
FIT for those >50, IDA, weight loss OR <60 with abdominal mass
Blood serum level of ferritin, total iron binding capacity (TIBC), iron, B12 and folate
Reticulocyte count: normal 2%: quantitative measure of concentration of immature RBC in circulation. If LOW: due to decreased production such as bone marrow disease (aplastic anaemia). If elevated: reflects bone marrow response to increased RBC destruction (haemolysis). Means the bone marrow producing RBCs too fast resulting in mass immature RBCs (reticulocytes)
OGD and colonoscopy to investigate for GI cause of unexplained iron deficiency anaemia (urgent referral)
Bone marrow biopsy is cause unclear
Target cells - abnormal RBC seen in liver disease, normal shape but abnormal centre. Nonspecific sign for abnormal RBC production
iron studies
serum iron: measures circulating iron most of which bound to transferrin. low in iron deficiency anaemia but also anaemia of chronic disease
total iron binding capacity TIBC: circulating transport protein for iron.
Low iron = high binding capacity due to need for it
High iron = low binding capacity
transferrin saturation (TSAT): ratio of serum iron to TIBC. decreased in iron deficiency anaemias
ferritin: circulating iron storage protein. also an acute phase reactant increases independently of iron storage in inflammatory disorders, infection, liver disease, heart failure and malignancy
Very low iron deficiency anaemias
can be normal in severely iron deficient patients who are very unwell
sickle cell and beta thalassaemia Hb electrophoresis
Foetal haemoglobin = HbF
Up to 6 months switches to HbA and HbA2 (adult Hb)
The majority is HbA; around 2% is HbF and HbA2
Sickle cell: presence of HbS cells instead of HbA as majority
Beta thalassaemia: majority of RBCs remains HbF with little HbA and HbA2
diagnostic pathway for anaemias
FBC and peripheral blood smear examinations:
MCV <80 - microcytic anaemia
Request serum iron studies - low iron and ferritin with high TIBC - iron deficiency anaemia.
If low/normal iron and low/normal ferritin with low TIBC - suggests component of anaemia of chronic disease with iron deficiency anaemia
MCV 80-100 - normocytic anaemia.
Request reticulocyte count - if <2% (hypoproliferative) - suggests leukaemia, aplastic anaemia, pure RBC aplasia or other bone marrow failure syndromes
If >2% (hyper proliferative) - suggests haemorrhage or haemolytic anaemias
MCV >100 (macrocytic anaemia) - are the cells megalocytes and segmented neutrophils on peripheral smear??
If present megablastic - suggests vitamin B12 and/or folate deficiency or drug induced anaemia
If absent: non-megaloblastic. suggests alcohol abuse, myelodysplastic syndrome, liver disease, congenital bone marrow failure syndromes
macrocytic anaemias
Megaloblastic:
B12 deficiency
Folate deficiency
Non-megaloblastic: Reticulocytes Liver disease Hypothyroid Pregnancy
vitamin B12 deficiency
Hydroxocobalamin
Vitamin B12 deficiency: causes macrocytosis. DNA synthesis requires B12 cofactor therefore deficiency leads to decreased erythrocyte DNA synthesis resulting in macrocytosis.
Hydroxocobalamin body stores are sufficient to last for anywhere between 2-5 years depending on need. Absorbed in the ileum after binding to intrinsic factor
Crohn’s disease is most likely IBD cause of B12 deficiency as this affects the entire GIT NOT ulcerative colitis as this is limited to the colon only
Serum cobalamin (B12) of <200nanograms/L (148 picomol/L)
In elderly B12 may be 10-160 picomol/L with no anaemia
Women taken OCPs may have lower B12 but no anaemia
causes of vit B12 deficiency
Dietary deficiency is rare and usually only occurs in elderly, those on strict vegan or vegetarian diets
Other causes of B12 deficiency: lack of intrinsic factor in patients who have undergone gastrectomy or have pernicious anaemia
Malabsorption of B12 secondary to small bowel bacterial overgrowth, tapeworm, ringworm, familial factors, Crohn’s, celiac or drugs like PPIs, metformin or H2 receptor antagonist.
Crohn’s disease is most likely IBD cause of B12 deficiency as this affects the entire GIT NOT ulcerative colitis as this is limited to the colon only
Pernicious anaemia: autoimmune condition affects the gastric mucosal lining leading to mucosal atrophy. Reduced number of parietal cells which secrete intrinsic factor (IF) which is essential for Vit B12 absorption. If +ve they definitely have anaemia, but if -ve recheck in 12 months or so to see if Abs have developed. Or anti parietal cell antibodies are present (can be present in elderly without pernicious anaemia)
People with pernicious anaemia are at increased risk of gastric cancer and thyroid disease so must be screened for thyroid function annually and have regular colonoscopy/any bowel red flags immediately investigated
vit B12 deficiency presentation
Fatigue Weakness Irritability Exercise intolerance Exertional dyspnoea (concerning at rest) Neuro involvement: Loss of cutaneous sensation Muscle weakness Optic neuropathy Vertigo Psychiatric disturbance: mild neurosis to severe dementia Symmetrical neuropathy, affecting legs more than arms Ataxia Paraesthesia
vit B12 deficiency investigations
FBC: macrocytic anaemia with hypersegmented neutrophils and/or oval macrocytes
Serum Vitamin B12 <200ng/L or high clinical suspicion on vit B12 deficiency. B12 acts as a coenzyme that converts MMA to other substances; therefore is increased in B12 def. And can indicate functional B12 deficiency. However in CKD this is always elevated so must only be used in renal functioning pts.
Non dietary cause suspected: intrinsic factor antibodies (IFAB)
