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
Haemolytic Anaemias
E:
A:
C:
Ix:
Tx:
Autoimmune Haemolytic Anaemia
E:
A:
C:
Ix:
Tx:
Thalassemia
E: Autosomal recessive. Major (symptomatic) and Minor (asymptomatic/mild anaemia).
A: Defect in either alpha or beta globin chains.
C: Splenomegaly. Chipmunk facies (pronounced forehead and cheekbones) - Major. RBCs in other locations. Poor growth and development (failure to thrive).
Ix:
FBC shows a microcytic anaemia
Haemoglobin electrophoresis is used to diagnose globin abnormalities
DNA testing can be used to look for the genetic abnormality
Tx:
Iron chelation (remove excess iron)
Splenectomy
BM transplant can potentially be curative
Alpha-thalassaemia
E: Autosomal recessive. CIS (same; Asians) or Trans (different; Africans) deletions.
A: Defects in alpha-globin chains. Chromosome 16. Disease severity is dependent on number of genes involved.
- 1 or 2 alpha globulin alleles; hypochromic and microcytic, but the Hb level would be typically normal. MILD anaemia.
- 3 alpha globulin alleles; hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease. SEVERE anaemia.
- 4 alpha globulin alleles (i.e. homozygote) then death in utero (Bart’s Hydrops fetalis).
Ix: FBC, Haemoglobin electrophoresis & DNA testing. Microcytic hypochromic anaemia. Target cells on blood smear. Fetal DNA (CVS or Amniocentesis).
Tx:
Monitoring FBC
Monitoring for complications
Blood transfusions
Splenectomy may be performed
BM transplant can be curative
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
B-Thalassemia Minor
E: Mediterranean, African and South-East Asians.
A: Heterozygous for gene deletion - one normal and one non-functioning gene.
C: Mild microcytic anaemia
Ix: FBC, Haemoglobin electrophoresis & DNA testing.
Tx:
Monitoring
No active treatment
B Thalassemia intermedia
E: Mediterranean, African and South-East Asians.
A:Homozygousfordefective gene - two defective genes or one defective and one deletion (non-functioning) gene.
C: Significant microcytic anaemia
Ix: FBC, Haemoglobin electrophoresis & DNA testing.
Tx:
Monitoring
Occassional blood transfusions
Iron chelation (if increased transfusions)
Sickle-Cell Anaemia
Epidemiology
Autosomal recessive. More prevalent in Africans. Selective advantage for malaria (reduced severity).
Aetiology
Sickle-cell shaped RBCs (beta-globin) due to deoxygenation. Prone to destruction, thus haemolytic anaemia. Haemoglobin S variant (HbS). Abnormal gene for beta-globin on chromosome 11.
Two forms:
Sickle Cell Trait: only one copy of the gene (heterozygous). Asymptomatic.
Sickle Cell Disease: two copies of the gene (homozygous). Symptomatic.
Clinical features (4-6m after birth)
Expansion of skull medullary cavities: elarged cheeks, ‘hair on end’ appearance of skull.
Extramedullary Haematopoesis: Hepatomegaly
Vaso-occlusion (multi-organ): Dactylitis (infancy), Pain crisis, AVN, Splenic infarct/sequestration, Recurrent infections, Stroke/Moya-Moya, Acute chest syndrome, Priaprism.
Investigations
Pregnant women at risk are offered testing.
Newborn heel prick test at 5d.
Normocytic anaemia. Raised reticulocyte count (compensatory).
Definitive Diagnosis:Haemoglobin Electrophoresis.
Management
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with Penicillin V (phenoxymethypenicillin)
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Blood transfusion for severe anaemia
BM transplant can be curative
Sickle Cell Crisis
Epidemiology
Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening.
Aetiology
They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
Clinical Features
Vaso-occlusive Crisis (AKA painful crisis)
Distal ischaemia. Associated with dehydration and raised haematocrit. Symptoms are typically pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis.
Splenic Sequestration Crisis
Splenic sequestration crisis is caused by RBCs 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
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 (fith disease aka ‘slapped cheek’).
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
Investigations
Crisis Management
Analgesia e.g. opiates
Rehydrate
Oxygen
Consider antibiotics if evidence of infection
Blood transfusion
Exchange transfusion: e.g. if neurological complications
NSAIDs such as ibuprofen should be avoided where there is renal impairment.
Longer-term management
Hydroxyurea increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
Pernicious Anaemia
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Acute Myeloid Leukaemia (AML)
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Acute Lymphocytic Leukaemia (ALL)
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Chronic Myeloid Leukaemia (CML)
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Chronic Lymphocytic Leukaemia (CLL)
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Hodgkin’s Lymphoma
Epidemiology
Bimodal age distribution - 20 and 75 years.
Aetiology
Proliferation of lymphocytes. Nodular sclerosing (70%)
Clinical features
Lymphadenopathy - asymmetrical non-tender and rubbery lymph nodes (pain with alcohol)
Fever (>38)
Weight loss (>10% in last 6m)
Night sweats
Investigations
Lactate dehydrogenase may be raised (non-specific)
Normocytic anaemia, eosinophilia
Definitive - Lymph node biopsy reveals presence of Reed Sternberg Cells (abnormally large B-Cells, multinucleated, ‘owl’)
Treatment
Chemotherapy (risk of leukaemia and infertility)
Radiotherapy (risk of cancer, hypothyroidism)
Non-Hodgkin’s Lymphoma
Epidemiology
Elderly with one-third of cases occurring in those over 75 years of age. RFs include immunosuppression (HIV), Viruses (EBV, Hep B/C), radiation or pesticide exposure (trichloroethylene).
Aetiology
Proliferation of B-Cell (70%) lymphocytes. Various types:
Burkitt lymphoma (B-cell) is associated with EBV, malaria and HIV. Young males.
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.
Diffuse large B cell lymphoma (B-cell) often presents as a rapidly growing painless mass in patients over 65 years.
Clinical features
Lymphadenopathy - asymmetrical non-tender and rubbery lymph nodes (cervical, axillary and inguinal)
Fever (>38)
Weight loss (>10% in 6m)
Night sweats
Extranodal disease (differentiating feature from Hodgkin’s): Gastric (dyspepsia, dysphagia, weight loss, abdominal pain), BM (pancytopenia, bone pain), lungs, skin, CNS (nerve palsies)
Compression syndromes: SVC Syndrome, Spinal Cord compression
BM infiltration: Anaemia, neutropenia or thrombocytopenia
Investigations
Lactate dehydrogenase may be raised (non-specific)
Definitive - Lymph node biopsy reveals presence of lymphocytic cells with ‘starry sky’ appearance
CT, MRI & PET for staging.
Treatment
Watchful waiting
Chemotherapy (risk of leukaemia and infertility)
Monoclonal antibodies such as rituximab
Radiotherapy (risk of cancer, hypothyroidism)
Stem cell transplantation
Burkitt’s Lymphoma
Epidemiology
Young males. Associated with EBV, Malaria and HIV.
Aetiology
Aggressive form of B-Cell lymphoma. C-myc gene translocation, usually t(8:14).
2 Forms
Endemic (African): involves maxilla or mandible (rapid focal tooth loosening)
Sporadic (American): GIT, pre/para-aortic lymph nodes
Clinical features
Extra-nodal involvement:
Investigations
Definitive: Lymph node biopsy reveals B-lymphocyte cells with ‘starry sky’ appearance.
Treatment
Chemotherapy; tendency to induce Tumour Lysis Syndrome:
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
Rasburicase is given alongside chemo to prevent this. Treatment of TLS involves
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
Primary Myelofibrosis
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Polycythemia Ruba Vera (PRV)
E:
A:
C:
Ix:
Tx:
Essential Thrombocythaemia
E:
A:
C:
Ix:
Tx:
Myelodysplastic Syndrome
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Von Willebrand Disease (VWD)
Epidemiology
Commonest inherited cause of haemophilia (abnormal bleeding). Autosomal dominant.
Aetiology
Deficiency, absence or malfunctioning of a glycoprotein called Von Willebrand Factor (VWF). Family history is relevant.
Clinical features
Patients present with a history of unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Epistaxis
HMB (menorrhagia)
Heavy bleeding during surgical operations
Investigations
Clinical diagnosis is made on history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations.
Prolonged _APTT (_intrinsic pathway) and bleeding time. Normal _PT(_extrinsic pathway). Low VWF.
Management
Managed in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):
Desmopressin can be used to stimulate the release of VWF
VWF infusion
Factor VIII is often infused along with plasma-derived VWF
Factor V Leiden
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Haemophillia
Epidemiology
X-linked recessive. Males (50% chance of affected if maternal carrier). Females (100% carriers if paternal carrier or 25% carriers if maternal carrier).
Aetiology
Severe bleeding disorder. Three forms:
Haemophilia A: Factor VIII deficiency
Haemophilia B: Factor IX deficiency
Haemophilia C*: Factor XI deficiency (ashkenazi jews)
*Autosomal recessive so can affect males and females.
Clinical features
Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.
Classically presents with spontaneous bleeding into joints (haemoathrosis) and muscles. If untreated this can lead to joint damage and deformity.
Investigations
Bleeding scores, coagulation factor assays and genetic testing.
PROLONGED APTT (intrinsic pathway)
NORMAL bleeding time, thrombin time, prothrombin time (PT) - extrinsic pathway
Treatment
Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:
Infusions of the affected factor (VIII or IX) for major bleed (antibodies against these can develop rendering these treatments ineffective). OR
Cryoprecipitate/FFP if infusions are unavailable
Desmopressin to stimulate the release of von Willebrand Factor (minor bleed)
Antifibrinolytics such as tranexamic acid
AVOID NSAIDS AND IM INJECTIONS
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
DVT & Thromboembolism
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Anticoagulation duration following provoked DVT
3 months (active cancer 3-6m)
Anticoagulation duration following unprovoked DVT
6 months
Causes of unprovoked DVT
X
Causes of provoked DVT
X
Chronic Fatigue Syndrome
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Haemochromatosis
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Hyperlipidaemia
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Hyposplenism
Epidemiology
Aetiology
Splenectomy
Sickle-cell
Coeliac disease, Dermatitis herpetiformis
Graves’ disease
Systemic lupus erythematosus
Amyloid
Clinical features
Investigations
Blood smear: Howell-Jolly bodies. Siderocytes
Management
Pancytopenia
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Wilson’s Disease
E:
A:
C:
Ix:
Tx:
Porphyrias
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Glucose-6-Phosphate Deficiency (G6PD)
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
Antiphospholipid Syndrome
Epidemiology
Aetiology
Clinical features
Investigations
Treatment
