Haematology Flashcards
Define anti-phospholipid syndrome.
The association of antiphospholipid antibodies with a variety of clinical features characterized by thromboses and pregnancy-related morbidity.
Antibodies:
- Lupus anticoagulant
- Anticardiolipin antibody
- Anti-beta-2-glycoprotein I
Explain the aetiology/risk factors of anti-phospholipid syndrome.
Pregnancy morbidity is defined as the loss of 3 or more embryos before the 10th week of gestation and/or 1 or more otherwise unexplained fetal deaths beyond the 10th week of gestation, and/or the premature birth of a morphologically normal neonate before the 34th week of gestation because of eclampsia, severe pre-eclampsia, or placental insufficiency.
Female patients with antiphospholipid antibodies and a history of pregnancy-related morbidity but no history of thrombosis are considered to have obstetric APS.
Patients who have antiphospholipid antibodies but no thrombotic or related obstetric complications (i.e., do not fit criteria for APS) are considered to have incidental antiphospholipid antibodies (aPL). Such patients are at increased risk of thrombosis, but it is not possible to identify which specific patients are at risk.
Risk factors:
- History of SLE, autoimmune rheumatological diseases, autoimmune haematological disorders
Summarise the epidemiology of anti-phospholipid syndrome.
1-5% of healthy individuals have aPL antibodies.
It is estimated that the incidence of APS is approximately 5 cases per 100,000 persons per year, and the prevalence is approximately 40-50 cases per 100, 000 persons.
Recognize the presenting symptoms of anti-phospholipid syndrome.
- History or current dx of vascular thrombosis
- History of pregnancy loss
- History of pregnancy associated morbidity
- History of SLE
- Features of thrombocytopenia
- Arthralgia / arthritis
- Livedo reticularis - mottled discolouration of the skin
- History of other rheumatological disorders or connective tissue disorders
- Cardiac murmur
- Oedema
- Seizure
- Headache
- Memory loss
- Signs of transverse myelopathy
- Limb discomfort, swelling
- Skin discoloration
- Ulcers
Recognize the signs of the anti-phospholipids syndrome on physical examination.
- History or current dx of vascular thrombosis
- History of pregnancy loss
- History of pregnancy associated morbidity
- History of SLE
- Features of thrombocytopenia
- Arthralgia / arthritis
- Livedo reticularis - mottled discolouration of the skin
- History of other rheumatological disorders or connective tissue disorders
- Cardiac murmur
- Oedema
- Seizure
- Headache
- Memory loss
- Signs of transverse myelopathy
- Limb discomfort, swelling
- Skin discoloration
- Ulcers
Identify appropriate investigations for anti-phospholipid syndrome and interpret the results.
1st Line:
- Lupus anticoagulant - positive on 2 occasions, 12 weeks apart
- Anti-cardiolipin antibodies - elevated on 2 occasions, 12 weeks apart
- Anti-beta-2-glycoprotein I antibodies - elevated on 2 occasions, 12 weeks apart
- ANA, double-stranded DNA, and extractable nuclear antigen antibodies - elevated in SLE
- FBC - thrombocytopenia (autoimmune or idiopathic thrombocytopenic purpura)
- Creatinine and urea - elevated if nephropathy is present
Think about:
- Venous Doppler ultrasound - DVT
- Venography or MRI - DVT
- MRI of thrombosis - DVT
- CT angiogram of the chest - PE
- Ventilation-perfusion (V/Q) scan - PE
- Cranial MRI - ischaemic stroke
- Echocardiography - valve vegetations
- Thrombophilia - negative
Define aplastic anaemia.
Defined by pancytopenia with hypocellular marrow and no abnormal cells.
At least 2 of the following peripheral cytopenias must be present:
- Hb <100 g/L
- Platelets <50 x 10^9/L
- Absolute neutrophil count <1.5 x 10^9/L
Bone marrow should show:
- Hypocellularity
- No evidence of dysplasia, blasts, fibrosis or abnormal infiltrate
Explain the aetiology / risk factors of aplastic anaemia.
Most often idiopathic.
Risk factors:
- Drug or toxin exposure
- Paroxysmal nocturnal haemoglobinuria (PNH)
- Recent hepatitis
- Pregnancy
- Autoimmune disease
- Family history
Summarise the epidemiology of aplastic anaemia.
The overall incidence of aplastic anemia in the study area was 2.34 cases per million population per year, and the mortality at 2 years was nearly one death per million per year. Both increased with age. Survival rates were 73% at 3 months, 57% at 2 and 5 years, and 51% at 15 years
Recognise the presenting symptoms of aplastic anaemia.
- Presence of risk factors
- History of recurrent infection
- Fatigue
- History of bleeding or easy bruising
- Premature hair loss / premature greying
- Hyperhidrosis
- Dysphagia
- Extensive dental caries or tooth loss
- Steatorrhoea
Recognise the signs of aplastic anaemia on physical examination.
- Pallor
- Conjunctival pallor
- Ecchymoses
- Tachycardia
- Dyspnoea
- Persistent warts
Uncommon:
- Hearing loss or deafness
- Short stature
- Pigmentation abnormalities
- Urogenital abnormalities
- Nail malformations
- Reticular rash
- Oral leukoplakia
- Epiphora
- Osteoporosis
- Skeletal dysplasia
- Monocytopenia
- Non-TB mycobacterial infections
- Pulmonary alveolar proteinosis
- Congenital lymphoedema
- Emberger syndrome
- Immunodeficiency
Identify appropriate investigations for aplastic anaemia and interpret the results.
1st Line:
- FBC with differential - 2 cytopenias among WCC, RCC, platelets, macrocytosis = inherited (Fanconi, dyskeratosis congenita), monocytopenia (GATA2-related)
- Reticulocyte count - low (hypoproductive - opposite to haemolytic anaemia which would be high)
- Bone marrow biopsy and cytogenetic analyses - hypocellular marrow with abnormal cell population
To consider:
- Serum B12 and folate levels - alternative cause of pancytopenia
- HIV testing - alternative cause of pancytopenia
- LFTs - abnormal = inherited (dyskeratosis congenita, Schwachman-Diamond), recent hepatitis, exposure to toxins
- Autoantibody screen - autoimmmune cause
- Flow cytometry for glycosylphosphatidylinositol (GPI) - anchored proteins
- CXR - if suspect malignancy, infection, lung fibrosis
- Ab USS - malignancy, Fanconi anaemia, telomeropathy
- Genetic tests - chromosomal breakage testing (diepoxybutane [DEB] test) for Fanconi anaemia; relevant genetic sequencing for other disorders, such as TERC, TERT, TINF2, DKC1 (for dyskeratosis congenita), SBDS (for Shwachman-Diamond syndrome), and GATA2 (for inherited GATA2-related disorder), telomere length (telomeropathies)
- CT - if telomeropathies or dyskeratosis congenita suspected
Dyskeratosis congenita = lung fibrosis, cirrhosis, non-cirrhotic portal hypertension
Define and discuss red cell transfusion, including indications and complications of transfusion.
Indications:
- Hb < 6g/dL or <3.7 mmoL/L
- Haematocrit < 18%
- Symptomatic anaemia - shortness of breath, dizziness, congestive HF, decreased exercise tolerance
- Acute sickle cell crisis
- Acute blood loss >30% blood volume
Complications:
- Allergic reactions
- Febrile, non-haemolytic reactions
- Immediate haemolytic reactions
- Delayed haemolytic reactions
Define and discuss platelet transfusion, including indications and complications of transfusion.
Indications:
- Thrombocytopenia or platelet function defect
- Correction of coagulopathy - if <50 x 10^9/ml
- Prophylactic transfusion - major surgery, invasive procedures, ocular surgery, neurosurgery, surgery with active bleeding
Examples:
- Leukaemia
- Aplastic anaemia
- AIDS
- Hypersplenism
- Sepsis
- Bone marrow transplant
- Radiation treatment
- Organ transplant or surgeries
Complications:
- Bacterial contamination
- Allergic reactions
- Febrile reactons
- VTE
- TRALI = Transfusion related acute lung injury
Avoid in those with TTP because it can worsen neurologic symptoms and acute renal failure due to the creation of new thrombi as platelets are consumed.
Avoid in those with heparin-induced thrombocytopenia (HIT) due to disseminated intravascular coagulation.
Define and discuss FFP transfusion, including indications and complications of transfusion.
Contents = ALL CLOTTING FACTORS:
- Fibrinogen (400-900 mg/unit)
- Plasma proteins - e.g. albumin
- Electrolytes
- Physiological anticoagulants - e.g. Protein C, Protein S, anti-thrombin, tissue factor pathway inhibitor
- Added anticoagulants
Definitive Indications:
- Factor deficiency
- Warfarin reversal (Vit K deficiency associated with active bleeding, high INR)
- Acute DIC
- TTP
Conditional Use:
- Massive transfusion
- Liver disease
- Cardio-pulmonary bypass
- Paediatric indications
- Deranged coagulation
No Justification:
- Hypovolaemia
- Plasma exchange
- Formula replacement
- Nutritional support
- Immunodeficiency
Complications:
- Disease transmission
- Anaphylactoid reactions
- Excessive intravascular volume = transfusion associated circulatory overload (TACO)
- Transfusion related acute lung injury (TRALI)
Define and discuss cryoprecipitate, including indications and complications of transfusion.
Contents:
- Fibrinogen (Factor I)
- Factor VIII
- Factor XIII
- VWF
- Fibronectin
Indications:
- Hypofibrinogenaemia
- Dysfibrinogenemia
- VW disease
- Haemophilia A
- Factor XIII deficiency
- Management of bleeding related to thrombolytic therapy
- DIC
- Uraemic bleeding tendency
- Reversing TPA with aminocaproic acid
DO NOT USE to prepare fibrin glue or treat sepsis
Complications:
- Haemolytic transfusion reactions
- Febrile, non-haemolytic reactions
- Allergic reactions from urticaria to anaphylaxis
- Septic reactions
- Transfusion-related acute lung injury = TRALI
- Transfusion-associated graft-versus-host disease
- Post-transfusion purpura
Define and discuss prothrombin complex concentrate, including indications and complications of transfusion.
Contents:
- Factor II
- Factor IX
- Factor X
May also contain:
- Factor VII
- Protein C
- Protein S
- Heparin - to stop early activation of factors
Indications:
- Reversal of acquired coagulation factor deficiency - e.g. induced by Vit K antagonist (WARFARIN)
- Acute major bleeding
- Peri-operative prophylaxis of hemorrhage with congenital factor deficiency
Contraindications:
- History of heparin-induced thrombocytopenia
- History of MI in last 3 months
- History of unstable angina within last 3 months
Complications:
- Embolism
- thrombosis
- Anxiety
- Device thrombosis
- Haemorrhage
- Hepatic function abnormal
- Hypertension
- Respiratory disorders
- Cardiac arrest
- Chills
- Circulatory collapse
- DIC
- Dyspnoea
- Heparin-induced thrombocytopenia
- Hypotension
- Nausea
- Skin reactions
- Tachycardia
- Tremor
Define disseminated intravascular coagulation (DIC).
An acquired syndrome characterized by activation of coagulation pathways, resulting in the formation of intravascular thrombi and depletion of platelets and coagulation factors.
May lead to:
- Vascular obstruction
- Ischaemia
- Multi-organ failure
- Spontaneous bleeding
Explain the aetiology / risk factors of disseminated intravascular coagulation (DIC).
Triggered by:
- Major trauma
- Organ destruction
- Sepsis or severe infection
- Severe obstetric disorders
- Some malignancies
- Major vascular disorders
- Severe toxic or immunological reactions
Risk factors:
- Major trauma / burn / organ destruction or sepsis / severe infection
- Severe obstetric disorders or complications
- Solid tumours and haematological malignancies
- Severe toxic or immunological reactions
- Major vascular disorders - large AA or giant haemangiomas
Summarise the epidemiology of disseminated intravascular coagulation (DIC).
DIC may occur in 30-50% of patients with sepsis, and it develops in an estimated 1% of all hospitalized patients. DIC occurs at all ages and in all races, and no particular sex predisposition has been noted.
Recognise the signs of disseminated intravascular coagulation (DIC) on physical examination.
- Petechiae
- Ecchymosis
- Gangrene
- Mental disorientation
- Hypoxia
- Hypotension
- GI bleeding
Recognise the signs of disseminated intravascular coagulation (DIC) on physical examination.
- Petechiae
- Ecchymosis
- Gangrene
- Mental disorientation
- Hypoxia
- Hypotension
- GI bleeding
- Tachycardia
- Purpura fulminans
Identify appropriate investigations for disseminated intravascular coagulation (DIC) and interpret the results.
Diagnosis:
- Presence of >1 known underlying condition causing DIC
- Abnormal global coagulation tests
Test results:
- Decreased platelet count
- Increased PT time
- Elevaed fibrin-related maker (D-dimer / fibrin degradation products)
- Decreased fibrinogen level
1st Line:
- Platelet count - low
- Prothormbin time - long
- Fibrinogen - low
- D-dimer / fibrin degradation products - high
- Activated partial thromboplastin time (aPTT) - unpredictable, long
- Imaging studies or other tests - variable, dependent on underlying disorder and areas of thrombosis & haemorrhage
Investigations to consider:
- Thrombin time - conversion of fibrinogen to fibrin, long
- Protamine test - positive (detects fibrin monomers in plasma)
- Factor V, VIII, X, XIII - low due to excessive consumption
Emerging tests:
- Inflammatory cytokines
- D-dimer (monoclonal antibody test)
- Anti-thrombin III
- FPA
- Prothrombin Fragment 1 and 2
Define haemolytic anaemia.
A number of conditions that result in the premature destruction of RBCs.
Explain the aetiology / risk factors of haemolytic anaemia.
Causes:
- Autoantibodies
- Medications - e.g. cephalosporins, dapsone, levodopa, levofloxacin, methyldopa, nitrofurantoin, NSAIDs, penicillins
- Underlying malignancy
- Hereditary conditions - e.g. hemoglobinopathies
Risk factors:
- Autoimmune disorders
- Lymphoproliferative disorders
- Prosthetic heart valve (mechanical, ball-and-cage devices, bileaflet valves)
- Family origin in Mediterranean, Middle East, Africa or Southeast Asia
- Family history of haemoglobinopathy or RBC membrane defects
- Paroxysmal nocturnal haemoglobinuria
- Recent exposure to cephalosporins, penicillins, quinine derivatives, or NSAIDs
- Recent exposure to naphthalene or fava beans
- Thermal injury
- Exceptional exertion
- Recent exposure to nitrites, dapsone, ribavirin, phenazopyridine
- Recent paraquat ingestion
- Malaria
- Babesiosis
- Bartonellosis
- Clostridium perfringens infection
- Haemophilus influenzae Type B infection
- Liver disease
Summarise the epidemiology of haemolytic anaemia.
Hemolytic anemia represents approximately 5% of all anemias. Acute AIHA is relatively rare, with an incidence of one to three cases per 100,000 population per year. Hemolytic anemias are not specific to any race.
Recognise the presenting symptoms of haemolytic anaemia.
- Presence of risk factors
- Fatigue
- Shortness of breath
- Dizziness
- Dark urine
- Active infections - e.g. malaria, Babesia, Bertonella, clostridial sepsis, pneumococci, E.coli, staphylococci
- Triggered by exposure to cold
Recognise the signs of haemolytic anaemia on physical examination.
- Pallor
- Jaundice
- Splenomegaly
- Dark urine
Identify appropriate investigations for haemolytic anaemia and interpret the results.
1st Line:
- FBC - low Hb
- MCHC - high (presence of spherocytes, reticulocytes)
- Reticulocyte count - high rectiulocyte percentage (>1.5%), absolute reticulocyte count, recticulocyte index
- Peripheral smear - schistocytes, spherocytes, elliptocytes, spur cells, blister cells, bite cells, tear drops, RBC inclusions (malaria, babesiosis, Bartonella infection)
- Unconjugated (indirect) bilirubin - high!
- LDH - high!
- Haptoglobin - low! - binds free Hb with low plasma values = increased free Hb
- Urinalysis - dipstick positive for blood, no RBCs = haemoglobinuria
To consider:
- Direct antiglobulin test (DAT or Coombs’) - positive = immune aetiology, negative = non-immune aetiology
- Creatinine, urea = thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome
- LFTs - high in liver disease
- Donath-Landsteiner antibody - cold-immune disease
- Hb electrophoresis - HbS = sickle cell, HbA2 and HbF = beta-thalassaemia
- Flow cytometry for CD55 / CD59 - abnormal (test for paroxysmal nocturnal haemoglobinuria clone - dark urine)
- G6PD fluorescent spot test and spectrophotometry - low G6PD activity
- ANA - positive if SLE (10% of cases)
Define haemolytic uraemic syndrome.
Characterised by a triad of microangiopathic haemolytic anaemia, thrombocytopenia and AKI.
Explain the aetiology / risk factors of haemolytic uraemic syndrome.
HUS
- Shiga toxin-producing Escherichia coli (STEC)
Atypical HUS
- Abnormalities in the alternative complement regulatory pathway
- Endothelial cell damage
- Microvascular thombosis
Risk factors:
- Ingestion of contaminated food or water
- Known community outbreak of Shiga toxin-producing E.coli
- Exposure to infected individuals in institutional settings
- Genetic predisposition to atypical HUS
- Bone marrow transplant
- Exposure to ciclosporin, chemotherapy, targeted cancer agents, quinine
- Pregnancy or post-partum related
Summarise the epidemiology of haemolytic uraemic syndrome.
Ninety percent of HUS cases occur in the paediatric population, due to Shiga toxin-producing Escherichia coli(STEC)
Atypical HUS can occur in adults, and in some children.
Recognise the presenting symptoms of haemolytic uraemic syndrome on physical examination.
- Diarrhoea
- Bloody diarrhoea
- Childhood (< 5 years)
Uncommon:
- Known community outbreak of Shiga toxin-producing E-coli
- History of ingestion of food that may have been contaminated with Shiga toxin-producing E-coli
- Unusual side effect seen after treatment with ciclosporin, chemotherapy, quinine
- Pregnancy or post-partum status
- Unusual adverse effect seen after bone marrow transplant
- Family history of possible HUS-like syndrome
Recognise the signs of haemolytic uraemic syndrome on physical examination.
- Diarrhoea
- Bloody diarrhoea
- Childhood (< 5 years)
Uncommon:
- Known community outbreak of Shiga toxin-producing E-coli
- History of ingestion of food that may have been contaminated with Shiga toxin-producing E-coli
- Unusual side effect seen after treatment with ciclosporin, chemotherapy, quinine
- Pregnancy or post-partum status
- Unusual adverse effect seen after bone marrow transplant
- Family history of possible HUS-like syndrome
Identify appropriate investigations for haemolytic uraemic syndrome and interpret the results.
1st Line:
- FBC - anaemia, thrombocytopenia
- Peripheral blood smear - presence of schistocytes
- Renal function / creatinine - increasing creatinine due to renal endothelial cell damage
- Serum electrolytes - sodium, potassium, chloride, bicarbonate, calcium and phosphorus = high K+, low or high Na+, acidosis, high PO4, low HCO3
- PT/PTT - normal to rule out DIC
- LDH - high (released from destroyed RBC)
- Haptoglobin - low (binds free Hb released by destroyed RBC)
- Stool culture on sorbitol-MacConkey agar - Shiga toxin-producing E.coli cannot ferment sorbitol, appears as white colonies
- PCR - positive
- Protein involved in complement regulation - abnormal levels of complement in familial and atypical HUS
Consider:
- Urinalysis - if renal involvement = haematuria, proteinuria or elevated creatinine level
- ADAMTS13 level - normal in most cases
- LFTs - transient transaminitis if hepatic involvement
- Serum amylase, lipase, glucose - increased if pancreatic involvement
Define haemophilia.
A bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor.
Explain the aetiology / risk factors of haemophilia.
Haemophilia A
- Deficiency of clotting factor VIII
Haemophilia B
- Deficiency of clotting factor IX
Acquired haemophilia
- Separate non-inherited condition
- Much rarer than congenital haemophilia
- Autoimmune-related aetiology
- No genetic inheritance pattern
Risk factors:
- Family history of haemophilia (congenital)
- Male sex (congenital)
- Age > 60 years (acquired)
- Autoimmune disorders - e.g. IBD, diabetes, hepatitis, pregnancy, postnatal, malignancy (acquired)
Summarise the epidemiology of haemophilia.
Hemophilia A is seen in about 1 in every 4,000–5,000 males worldwide, compared with hemophilia B, which is estimated to be in 1 in every 20,000 men. Hemophilia C, a much rarer form of the disease, is estimated to occur in about 1 case per 100,000 people in the U.S.
Almost exclusively in males due to X-linked recessive pattern of inheritance.
Recognise the presenting symptoms of haemophilia.
- Presence of risk factors
- History of recurrent or severe bleeding
- Bleeding into muscles
- Prolonged bleeding following heel prick or circumcision
- Mucocutaneous bleeding
- Haemarthrosis
- Intracranial bleeding
- Fatigue
- Menorrhagia and bleeding following surgical procedures or childbirth (female carriers)
Recognise the signs of haemophilia on physical examination.
- Excessive bruising
- Haematoma
- Extensive cutaneous purpura (acquired)
- GI bleeding (haematemesis or melena)
- Haematuria
- Distended and tender abdomen
- Pallor
- Tachycardia
- Tachypnoea
- Hypotension
Identify appropriate investigations for haemophilia and interpret the results.
1st Line:
- aPTT - prolonged
- Plasma Factor VIII and Factor IX assay - low (use to determine severity)
- Mixing study - aPTT corrected by incubating patient plasma with normal plasma in congenital, not corrected if antibodies present in immune acquired
- FBC - normal, low Hb if bleeding
- PT - normal
- Plasma vWF assay - normal
- Plasma Factor V, VII, XI, XII assay - normal
- Closure time/bleeding time and platelet aggregation studies - normal
- Serum AST and ALT - normal (check for liver disease)
- Plain XR of bony sites - demonstrate findings of acute joint bleeding (haemarthrosis)
- Antenatal factor VIII or IX mutation analysis by amniocentesis or chorionic villus sampling (CVS) - specific genetic mutation identified
Consider:
- Head or neck CT
- Head or neck MRI
- Abdominal ultrasound or CT AP scan
- OGD or colonoscopy
- Blood factor VIII or IX mutation analysis
- Plasma factor VIII or IX inhibitor screen
- Bethesda assay / modified Bethesda assay on plasma sample - low-responder inhibitor
Define immune thrombocytopenic purpura (ITP).
Primary = a haematological disorder characterised by isolated thrombocytopenia (platelet count <100 x 10^9/L) in absence of identifiable cause
Secondary = all forms of ITP where associated medical conditions or precipitants can be identified.
Distinction clinically relevant due to different natural histories and treatments, including need to treat the underlying condition in secondary ITP.
Explain the aetiology / risk factors of immune thrombocytopenic purpura (ITP).
Primary = thrombocytopenia due to autoimmune destruction and involves antibody destruction of peripheral platelets.
Risk factors:
- Women of childbearing age
- Age <10 or >65 years
Summarise the epidemiology of immune thrombocytopenic purpura (ITP).
Typically found in children often with a preceding viral illness and an abrupt onset. There is a female preponderance among adults, who may present with thrombocytopenia with or without bleeding.
The prevalence (how many adults have ITP at any time) is 9.5 cases per 100,000. The annual prevalence is estimated at 5.3 per 100,000 among children; because children with ITP usually recover, the number of children who have ITP at any one time is almost equal to those diagnosed annually.
Recognise the presenting symptoms of immune thrombocytopenic purpura (ITP).
- Presence of risk factors
- Bleeding
- Absence of systemic symptoms - e.g. fever, weight loss, arthralgia, skin rash, skin rash, alopecia, venous thrombosis
- Absence of medicines that cause thrombocytopenia - e.g. heparin, alcohol, quinine / quinidine, sulfa drugs
- Absent splenomegaly or hepatomegaly
- Absent lymphadenopathy
Recognise the signs of immune thrombocytopenic purpura (ITP) on physical examination.
- Presence of risk factors
- Bleeding
- Absence of systemic symptoms - e.g. fever, weight loss, arthralgia, skin rash, skin rash, alopecia, venous thrombosis
- Absence of medicines that cause thrombocytopenia - e.g. heparin, alcohol, quinine / quinidine, sulfa drugs
- Absent splenomegaly or hepatomegaly
- Absent lymphadenopathy
Identify appropriate investigations for immune thrombocytopenic purpura (ITP) and interpret the results.
1st Line:
- FBC - low platelets < 100 x 10^9/L
- Peripheral blood smear - low platelets (distinguishes between true thrombocytopenia and pseudothrombocytopenia occuring when there is insufficient collection in 0.1% of adults)
Consider:
- HIV serology
- H.pylori breath test or stool antigen test
- Hepatitis C serology
- TFTs - both hyper and hypothyroidism cause thrombocytopenia
- Quantitative immunoglobulins - reveal common variable immunodeficiency or selective IgA deficiency
- Bone marrow biopsy / aspiration - increased megakaryocytes, no malignancy or cytometry or cytogenetic abnormalities
- Pregnancy test
Define multiple myeloma.
A plasma cell dyscrasia characterized by terminally differentiated plasma cells, infiltration of bone marrow by plasma cells and the presence of monoclonal immunoglobulin (or immunoglobulin fragment) in serum and/or urine.
Explain the aetiology / risk factors of multiple myeloma.
Risk factors:
- Osteolytic bone disease
- Anaemia
- Renal failure
- Abnormal free light-chain ratio
- Monoclonal gammopathy of undetermined significance (MGUS)
- Family history
- Radiation exposure
- Petroleum products exposure
Summarise the epidemiology of multiple myeloma.
Myeloma incidence rates are projected to rise by 11% in the UK between 2014 and 2035, to 12 cases per 100,000 people by 2035. [1] This includes a larger increase for males than for females. It is projected that 8,888 cases of myeloma (5,229 in males, 3,659 in females) will be diagnosed in the UK in 2035.
Recognise the presenting symptoms of multiple myeloma.
- Anaemia
- Bone pain
- Monoclonal gammopathy of undetermined significance (MGUS)
- Infections
- Fatigue
- Renal impairment
Recognise the signs of multiple myeloma on physical examination.
- Anaemia
- Bone pain
- Monoclonal gammopathy of undetermined significance (MGUS)
- Infections
- Fatigue
- Renal impairment
Identify appropriate investigations for multiple myeloma and interpret the results.
1st Line:
- Serum / urine electrophoresis - paraprotein spike, hypogammaglobulinaemia
(IgG >35g/L or IgA >20g/L and light chain urinary excretion >1g/day)
- Skeletal survey - osteopenia, osteolytic lesions, pathological fractures
- Whole-body, low-dose computed tomography (WBLD-CT) - osteolytic lesions (>5mm in diameter), pathological fractures
- Serum-free light-chain assay - increased concentrations of free light chain in serum
- Bone marrow aspirate and biopsy - monoclonal plasma cel infiltration in bone marrow >10%
- Serum calcium - hypercalcaemia
- FBC - anaemia
- Creatinine, urea - renal impairment (creatinin >176 mmol/L)
- Serum beta-2-microglobulin - correlates with clinical stages, <3.5mgd/dL (stage 1), >5.5mgL (Stage 3)
- Serum albumin - prognostic significance - >35g/L (stage I)
Consider:
- Whole body MRI - >1 focal lesions on MRI study, bone marrow infiltration
- 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) - bone disease, bone marrow infiltration
- CRP - high or increasing
- LDH - higher = more extensive disease
- Cytogenetics & fluorescence in situ hybridisation analysis - chromosomal trisomies or monosomies
Define Hodgkin’s lymphoma.
An uncommon haematological malignancy arising from mature B cells.
Explain the aetiology / risk factors of Hodgkin’s lymphomas.
Characterized by the presence of Hodgkin’s cells and Reed-Sternberg cells.
Risk factors:
- History of EBV infection
- Family history
- Young adults from higher socio-economic class
- HLA types
- Jewish ancestry
Summarise the epidemiology of Hodgkin’s lymphomas.
Hodgkin’s lymphoma is a rare cancer of the lymphatic system that affects the B-lymphocytes and leaves a patient susceptible to infection. Estimates suggest that around 1 in 25,000 people are affected by this cancer every year and the condition accounts for just under 1% of all cancers that occur worldwide.
Recognise the presenting symptoms of Hodgkin’s lymphoma.
B-Symptoms:
- Fevers
- Night sweats
- Weight loss
Common presentation:
- Painless
- Cervical and/or supraclavicular lymphadenopathy
- Young adult
Uncommon factors:
- Unexplained fevers
- Night sweats
- Weight loss
- Dyspnoea
- Cough
- Chest pain
- SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins
- Abdominal pain
- Generalised pruritus
- Alcohol-induced pain at involved sites
- Hepatomegaly and / or splenomegaly
- Tonsillar enlargement
Recognise the signs of Hodgkin’s lymphoma on physical examination.
B-Symptoms:
- Fevers
- Night sweats
- Weight loss
Common presentation:
- Painless
- Cervical and/or supraclavicular lymphadenopathy
- Young adult
Uncommon factors:
- Unexplained fevers
- Night sweats
- Weight loss
- Dyspnoea
- Cough
- Chest pain
- SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins
- Abdominal pain
- Generalised pruritus
- Alcohol-induced pain at involved sites
- Hepatomegaly and / or splenomegaly
- Tonsillar enlargement
Identify appropriate investigations for Hodgkin’s lymphoma and interpret the results.
- FBC - low Hb and platelets, WBC may be high or low
- Metabolic panel - normal
- ESR - elevated
- CXR - mediastinal mass, large mediastinal adenopathy (negative prognostic factor)
- PET-CT scan - involved sites appear FDG-avid (bright)
- Gallium scan - bright involved sites
- Contrast CT neck, chest and AP - enlarged lymph nodes
- Excisional lymph node biopsy - Hodgkin’s cells
- Immunohistochemical studies - CD30-positive, CD15-positive, CD45-negative, CD20 positive
Investigations to consider:
- Bone marrow biopsy - Hodgkin’s cells
- TFTs - abnormal in patients who receive radiotherapy to neck
- Echo or multi-gated acquisition (MUGA) scan
- Pulmonary function tests
Define non-Hodgkin’s lymphoma.
A heterogeneous group of malignancies of the lymphoid system.
Explain the aetiology / risk factors of non-Hodgkin’s lymphoma.
- Malignant lymphoid cells retain many qualities of their normal counterparts - e.g. defending organism from external and internal (neoplastic) threats
- Boundaries between leukaemias and lymphomas are blurred - e.g. acute alymphocytic leukaemia and acute lymphoblastic lymphoma, chronic lymphocytic leukaemia and small lymphocytic lymphoma
- Depends on relative presence of solid phase (lymphoma) versus circulating phase (leukaemia)
Risk factors:
- Age > 50 years
- Male
- Immunocompromised host
- Epstein-Barr virus (EBV)
- HTLV-1 virus
- Herpes Virus-8
- H.pylori
- Coeliac disease
- HIV
- Hepatitis C virus
- Sjogren’s syndrome
- Wiskott-Aldrich Syndrome
- Ataxia - Telangiectasia
- Organ transplant
- Borrelia burgdoferi
- Rheumatoid arthritis
- SLE
- Common veriable immunodeficiency
- Chediak-Higashi syndrome
- Klinefelter’s syndrome
- Pesticides
- Phenoxyherbicides
- Breast implants
