Haematology Flashcards
Describe the general basics of blood compatibility
O Groups are universal RBC donors, but can be only be given O RBCs as anti-A and anti-B are present in plasma
A groups have anti-B in plasma, so therefore neither B or AB can be given. They can be given group O or A.
AB can receive any blood group, but cannot be a donor with the exception of plasma
Management of Blood Transfusion Reactions
X
Blood Transfusion Reactions
X
RhD Antigen
- RhD _+ve individuals can either be heterozygous (Dd) or homozygous (DD)
- RhD -ve individuals will be homozygous for dd
- RhD is immunogenic, so can easily cause sensitisation events
RBC Alloantibodies
Tend to be IgG antibodies, therefore delayed haemolytic transfusion reactions
Describe the principles of pre-transfusion testing
- Group & Screen aka Group & Save
- Identify ABO & RhD Group
- Ab Screen to detect presence of Abs in plasma to main RBC antigens
- Electronic if negative Ab Screen
- Wet if Abs or other concerns
What are the indications for Transfusion?
Benefits vs. Risk
- Benefits: Increase O2 Haemoglobin
- Risks: infection, prion - variant cjd, acute reaction, fluid overload
- Asymptomatic individuals do not require transfusion unless haemoglobin is very low (<70g/L)
- NICE Guidelines state transfuse patients with Hb <70g/l, aiming for 70-90g/L
- If patient is chronically hypoxic or heart issues with anaemia, transfusion may be required at higher haemoglobin
- Restrictive thresholds can be implemented for individuals with normal bone marrows
Alpha-1 Anti-trypsin Deficiency
Causes of Thrombocytopenia
Problems with Production
Sepsis
B12 or folic acid deficiency
Liver failure causing reduced thrombopoietin production in the liver
Leukaemia
Myelodysplastic syndrome
Problems with Destruction
Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors)
Alcohol
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Heparin-induced thrombocytopenia
Haemolytic-uraemic syndrome
Idiopathic Immune Thrombocytopenia (ITP)
E: Commonest form of thrombocytopenia. Older females.
A: Immune-mediated platelet destruction. Following a recent infection (children). Chronic (adults)
C: Purpuric rash, commonly affecting shins. Bleeding (epistaxis)
Ix: Diagnosis of exclusion. Platelets <150. Antiplatelet autoantibodies. BM aspiration (megakaryocytes). NO Schistiocytes.
Tx:
1st Line: Prednisolone (steroids)
IV immunoglobulins (active bleeding/invasive procedure)
Rituximab (a monoclonal antibody against B cells)
Splenectomy (if platelets < 30 after 3 months of steroid therapy)
Thrombotic Thrombocytopenic Purpura (TTP)
E: Rare.
A: Defect of ADAMS13 protein (responsible for VWF inactivation, thus clotting). VWF overactivity - platelets used up. Results in microangiopathy; blood clots in small vessels.
C: Purpuric rash. Anaemia. Thrombocytopenia. Fever.Nerologicsymptoms (aphasia, diplopia, clumsiness).Renal dysfunction.
Ix: Increased bleeding time. Schistiocytes present on smear.
Tx:
Plasma exchange
Steroids
Rituximab
Heparin Induced Thrombocytopenia (HIT)
E:
A: Heparin-induced antibodies target platelets - Platelet Factor 4 (PF4). Clotting factors are activated. Induced hypercoagulable state. Thrombosis. Thrombocytopenia.
C: DVTs. Skin changes.
Ix: HIT antibodies.
Tx: Stop heparin. Use alternative anticoagulant. Patients are at an increased risk of clotting events.
https://www.ahajournals.org/doi/full/10.1161/circulationaha.106.632653
Disseminated Intravascular Coagulation (DIC)
E:
A: Widespread clotting activation.
C: Bleeding, Sepsis, Trauma, Obstetric (HELLP, fluid embolism, haemolysis)
Ix: Thrombocytopenia. Increased bleeding time. Increased PT/PTT. Increased D-Dimer. Reduced fibrinogen (clotting factor). Schisiocytes on smear (microangiopathic haemolytic anaemia). Microthrombi.
↓ platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
Tx: Supportive, blood components and treatment of underlying disorder.
Causes of Microcytic Anaemia
Causes (TAILS)
T – Thalassaemia*
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia (congenital)
A question sometimes seen in exams gives a history of a normal haemoglobin level associated with a microcytosis. In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra vera which may cause an iron-deficiency secondary to bleeding.
New onset microcytic anaemia in elderly patients should be urgently investigated to exclude underlying malignancy.
*in beta-thalassaemia minor the microcytosis is often disproportionate to the anaemia
Causes of Normocytic Anaemia
Causes of normocytic anaemia (3As & 2Hs)
A – Acute blood loss
A – Anaemia of Chronic Disease (also microcytic)
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
Chronic kidney disease
Causes of Macrocytic Anaemia
Impaired DNA synthesis - abnormally large cell
Megaloblastic
vitamin B12 deficiency
folate deficiency
Normoblastic
Alcohol
Liver disease
Hypothyroidism
Pregnancy
Reticulocytosis (haemolytic anaemia or blood loss)
Myelodysplasia
Drugs: cytotoxics (Azathioprine)
Iron Deficiency Anaemia
E: Most common form of anaemia.
A: Reduced dietary intake (infants, vegetarian). Reduced absorption (coeliac, IBD, gastrectomy). Increased demand (pregnancy, childhood). Blood loss (gastric/colon cancer, peptic/duodenal ulcer, HMB, H.pylori).
C: Fatigue. SOB. Palpitations. Pica (abnormal dietary cravings). Hair loss.
Signs:
Pale skin
Brittle hair and nails
Conjunctival pallor
Tachycardia
Raised respiratory rate
Koilonychia (spoon-shaped nails)
Angular chelitis (mouth fissures)
Atrophic glossitis (smooth tongue)
Ix: FBC, Blood film. Microcytic MCV. Low ferritin (less stored). High Transferrin (TIBC - unbound transferrin). Hypochromic (pale). Poikilocytosis. Anisocytosis.
Tx:
- OGD & Colonoscopy to investigate for a GI cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected gastrointestinal cancer.
- BM biopsy may be required if the cause is unclear.
1st Line: Ferrous Sulfate 200 mg
2nd Line: Ferrous gluconate 300mg
Recheck Hb response after 2-4 weeks
IDA Urgent Referral Criteria
Urgently refer people with iron deficiency anaemia using a suspected cancer pathway for an appointment within 2 weeks if they are:
Aged 60 years or over.
Consider an urgent referral for people with iron deficiency anaemia using a suspected cancer pathway for an appointment within 2 weeks if they are:
Aged under 50 years AND present with rectal bleeding.
Plummer Vinson Syndrome
Associated with IDA. Triad of:
Oesophageal Webs
IDA
Dysphagia/Glossitis
Sideroblastic Anaemia
Epidemiology
Rare. Congenital (x-linked) mainly affecting males. Acquired: Alcohol abuse, Lead poisoning, Vitamin B6 deficiency. TB therapy (Isoniazid).
Aetiology
ALAS2 mutation. Abnormal haem production - impaired incorporation of iron to form haem. Immature and dysfunctional RBCs.
Clinical Features
General features of anaemia; similar features to haemochromatosis due to iron deposition (fatigue, heart disease, liver damage, enlarged spleen, renal failure and diarrhoea).
Investigations
BM biopsy - presence of ring sideroblasts.
FBC usually shows a moderate degree of anaemia.
Pappenheimer bodies and basophilic stippling on blood film.
MCV is normal or increased, but can be low.
High serum iron and ferritin. Low TIBC.
The blood film shows a dimorphic population of both normal and hypochromic red blood cells.
Management
Treatment is mainly supportive
Red cell transfusion is given for symptomatic anaemia
Iron chelation with desferrioxamine should be considered after 20-25 units of red cells have been received.
Avoid alcohol and reduce vitamin C intake, as these increase iron absorption
Anaemia of Chronic Disease
Epidemiology
Chronic inflammatory disease states such as COPD, DM, Autoimmune disorders, infections and malignancy.
Second most common anaemia.
Aetiology
Continuous inflammation by Chronic disease state results in impaired iron metabolism and hence RBC production and lifespan.
Clinical Features
General clinical features of anaemia of Fatigue, Pallor and SOB.
Investigations
Normocytic anaemia. Low iron. Normal-low transferrin (TIBC). Low transferrin saturation. Normal/increased ferritin.
Treatment
Treat underlying cause
Lead Poisoning
Epidemiology
Classically presents in painters/children playing with old paint.
Aetiology
Defective ferrochelatase and ALA dehydratase function
Clinical features
Abdominal pain
Peripheral neuropathy (mainly motor)
Fatigue
Constipation
Blue lines on gum margin (only 20% of adult patients, very rare in children)
Investigations
Blood Lead Level (> 10 mcg/dl is significant)
FBC: microcytic anaemia.
Blood film: red cell abnormalities including basophilic stippling and clover-leaf morphology
raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria
urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)
Treatment
Dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
Dimercaprol
Vitamin B12 Deficiency
Epidemiology & Aetiology
Impaired absorption - pernicious anaemia (autoimmune destruction of intrinsic factor/parietal cells). Crohn’s Disease (damage to enterocytes in terminal ileum). Gastric bypass. Fish tapeworm. Bacterial overgrowth.
Reduced dietary intake (vegans)
Clinical Features
Glossitis - painful large red tongue
Neurological: Poor reflexes, peripheral neuropathy (demyelination) with symmetrical parasthesia affecting legs > arms.
Subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
Neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
SOB
Fatigue
IHD
Investigations
FBC: Macrocytic megaloblastic anaemia. Pancytopenia (Low RBC, WBC and Platelets).
Blood Smear: Hypersegmented neutrophils.
Anti-intrinsic factor antibodies (pernicious anaemia)
Management
Pernicious Anaemia: IM hydroxocobalamin (B12)
Neurological involvement: IM hydroxocobalamin (B12)
Dietary: Initially IM hydroxocobalamin (B12) for 2 weeks then oral cyanocobalamin tablets 50–150 micrograms daily
https://cks.nice.org.uk/topics/anaemia-b12-folate-deficiency/management/management/
Folate Deficiency
Epidemiology
Associated with Neural Tube Defects (NTDs) - anencephaly or spina bifida.
Aetiology
Increased demand (pregnancy)
Reduced dietary intake (> 6 weeks)
Reduced absorption (excessive alcohol, drugs - phenytoin, trimethoprim, sulfasalazine and methotrexate)
Clinical Features
Glossitis - painful large red tongue
Neurologic: Poor reflexes, peripheral neuropathy (demyelination), memory problems.
SOB
Fatigue
IHD (increased homocysteine)
Investigations
FBC: Macrocytic megaloblastic anaemia. Pancytopenia (Low RBC, WBC and Platelets).
Blood Smear: Hypersegmented neutrophils.
Anti-intrinsic factor antibodies (pernicious anaemia)
Management
Pregnancy: folate supplementation: 400 micrograms (μg) daily before pregnancy and throughout the first 12 weeks. 5 milligrams of folic acid a day for women who are planning a pregnancy, or are in the early stages of pregnancy, if:
- they (or their partner) have a NTD
- have had a previous baby with a NTD
- (or their partner) have a family history of NTD
- have diabetes.
- have epilepsy.
Absorbtion: Stop offending medications
Dietary: Prescribe oral folic acid 5 mg daily for 4 months
https://cks.nice.org.uk/topics/anaemia-b12-folate-deficiency/management/management/
Fanconi Anaemia
Epidemiology
Autosomal recessive
Aetiology
Clinical features
Haematological: aplastic anaemia (with pancytopenia), increased risk of AML
Neurological: developmental delay
‘Bird-like’ facies
Skeletal abnormalities: short stature, thumb/radius abnormalities
Cafe au lait spots
Investigations
Treatment
Aplastic Anaemia
Epidemiology
Peak incidence ~30 years of age
Aetiology
Generally idiopathic. Definable causes: radiation & toxins. Congenital: Fanconi anaemia, dyskeratosis.
Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Toxins: benzene
Infections: parvovirus, hepatitis
Commonest form is autoimmune destruction of Haematopoetic Stem Cells (HSCs).
Clinical Features
Fatigue
Pallor
Mucosal Bleeding
Petichiae
Recurrent infections
Investigations
FBC: Anaemia & Pancytopenia (Low RBC, WBC, Platelets)
Increased EPO
Reduced reticulocyte count
Definitive Diagnosis: BM Biopsy with low HSCs, normal cellular morphology in absence of infiltrative disorder
Treatment
Dependent on age
Allogenic stem cell transplant
Immunosuppressants
B-Thalassemia Major
E: Mediterranean, African and South-East Asians.
A: Homozygous for deletion genes. Free alpha chains form inclusions in RBCs - leads to haemolysis of RBCs. Ultimately causes increased RBC production.
C: Splenomegaly. Failure to thrive in early childhood (first 3-6 months of life). Severe microcytic anaemia. Chipmunk facies (excess RBC production). Jaundice (byproduct of RBC breakdown). Secondary Haemochromatosis (excess iron).
Ix: FBC, Haemoglobin electrophoresis (low HbA, high HbF and HbA2) & DNA testing. Microcytic hypochromic anaemia. High Iron, ferritin and transferrin (TIBC). Target Cells present on blood smear.
Tx:
Iron chelation (remove excess iron); deferoxamine
Splenectomy
BM transplant can potentially be curative
Staging of Lymphomas (Ann Arbor)
Stage 1: Confined to one region of lymph nodes.
Stage 2: In more than one region but on the same side of the diaphragm (either above or below).
Stage 3: Affects lymph nodes both above and below the diaphragm.
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.
Myeloma (multiple)
Epidemiology
>60 years with unexplained bony pain (lower back/thoracic). Second most common haematological malignancy.
Aetiology
Plasma (B lymphocyte) cells
Clinical features (CRAB)
C – Calcium (elevated due to inreased osteoclastic activity). Confusion, muscle weakness, constipation, thirst, and polyuria (due to hypercalcaemia).
R – Renal failure (immunoglobin deposition)
A – Anaemia (normocytic, normochromic) from replacement of bone marrow.
B – Bone lesions/pain (lytic lesions on X-ray; ‘raindrop’ skull). Lower back. Sensory loss, paraesthesia, limb weakness, walking difficulty, and sphincter disturbance (due to spinal cord compression).
Investigations (BLIP)
B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum _Immunoglobulins (_IgA/IgG proteins)
P – Serum Protein electrophoresis
Pancytopenia: Anaemia (‘crowding-out’ BM) and Thrombocytopenia (FBC); Raised urea and creatinine (U&E) and Raised calcium. Raised ESR.
Raised Plasma Viscosity (PV): easily bruise/bleed.
Imaging: X-rays of symptomatic areas (to rule out pathological fractures)
Blood film: rouleaux formation
Definitive diagnosis: BM Biopsy (aspiration and trephine)
Treatment
First line treatment usually involves a combination of chemotherapy with:
Bortezomid
Thalidomide
Dexamethasone
Autologous Stem Cell transplant - younger patients
VTE prophylaxis (LMWH or aspirin)
Myeloma bone disease can be improved using bisphosphonates (zoledronic acid). These suppress osteoclast activity.
Radiotherapy to bone lesions can improve bone pain.
Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain
Platelet vs. Coagulation disorders
Platelet Disorders (Primary)
Affects mucous membranes (gingival, GI, vaginal)
Petechiae (multiple)
Prolonged bleeding from cuts
Family history rare
Prolonged Bleeding Time
Examples include thrombocytopenias i.e. VWD, ITP
Coagulation Disorders (Secondary)
Affects joint spaces (haemarthrosis)
Ecchymoses (large bruising)
Haematomas (muscles)
Delayed-onset bleeding
Family history common
Prolonged APTT (Intrinsic pathway) & PT (extrinsic pathway). Normal bleeding time
Examples include Haemophilia A/B, Factor V Leiden, LD, DIC, Vitamin K deficiency
