Haem conditions Flashcards
1
Q
Macrocytic anaemia
- Definition
- Aetiology/RF
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
- Management
- Complications
- Prognosis
A
- Anaemia associated with high MCV of erythrocytes
- Megaloblastic: when bone marrow unusually large, structurally abnormal, immature red cells; deficiency of B12/folate is the cause
- Deficiency of vit B12: Reduced absorption, reduced intake (vegans), abnormal metabolism (congenital transcobalamin II deficiency)
- Deficiency of folate: reduced intake (alcoholics, elderly, anorexia), increased demand (pregnancy, lactation, malignancy), reduced absorption, jejunal disease (coeliac), drugs (phenytoin)
- Drugs: methotrexate, hydroxyurea, azathioprine, zidovudine
- NON-MEGALOBLASTIC: alcohol excess, liver disease, myelodysplasia, multiple myeloma, hypothyroidism, haemolysis, drugs
- more common in elderly females; pernicious anaemia most common cause in West
- Non-specific = tiredness, lethargy, dyspnoea; FHx of AI disease; previous GI surgery; syx of the cuase
- Anaemia: pallor, tachycardia, SOB; Pernicious anaemia: mild jaundice, glossitis, angular stomatitis, weight loss; B12 deficiency: peripheral neuropathy, ataxia, subacute combined degeneration of spinal cord, optic atrophy, dementia
- Bloods: FBC: high MCV, pancytopaenia in megaloblastic anaemia, exclude reticulocytis; LFTs (high billirubin), ESR, TFT, serum vit b12, red cell folate, anti-parietal cell and anti-intrinsic factor Ab, serum protein electrophoresis for dense band in myeloma
- Blood film: large erythrocytes; megaloblastic: megaloblasts and hypersegmented neutrophil
- Schilling test: for pernicious anaemia, B12 only absorbed when given IF
- Bone marrow biopsy
- Investigations for cause
- Pernicious anaemia: IM hydroxycobalamin for life; folate: oral folic acid, and if b12 def present, treated before folic acid def
- Pernicious has increased risk of gastric cancer; pregnancy: folate def increases risk of neural tube defects
- majority treatable if no complications
2
Q
Microcytic anaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
- Management
- Complications
- Prognosis
A
- Anaemia associated with a low MCV <80fl
- Iron deficiency - most common, caused by blood loss (GI), reduced absorption (small bowel disease), increased demands (growth, pregnancy), reduced intake (vegans)
- Anaemia of chronic disease
- Thalassaemia
- Sideroblastic anaemia - abnormality of haem synthesis, can be inherited/secondary
- Iron deficiency anaemia is the most common form of anaemia worldwide
- Non-specific: tiredness, lethargy, malaise, dyspnoea, pallor, exacerbation of ischaemic conditions (angina, intermittent claudication)
- Lead poisoning: can cause microcytic anaemia; anorexia, N/V, abdo pain, constipation, peripheral nerve lesions
- Anaemia: pallor, brittle nails and hair, koilonychia, glossits, angular stomatits
- Lead poisoning: blue gum line, peripheral nerve lesions, encephalopathy, convulsions, reduced consciousness
- Bloods: FBC (low Hb, low MCV, reticulocytes), serum irone, total iron binding capacity is high in iron def, serum ferritin (low), serum lead
- Blood film:
- IDA: microcytic, hypochromic, anisocytosis, poikilocytosis
- Sideroblastic anaemia: dimorphic blood film, hypochromic microcytic cells
- Lead poisoning: basophilic stippling
- Hb electrophoresis: for thalassaemia
- Sideroblastic anaemia: ring sideroblasts in bone marrow
- Special inv if IDA >40, male and/or post menopausal women: upper GI endoscopy, colonoscopy, haematuria
- Blood film:
- IDA: oral iron supplements;
- sideroblastic anaemia: treat cause, pyridoxine in inherited forms, blood transfusion and iron chelation considered if no response
- Lead poisoning: remove source, dimercaprol, D-penicillinamine
- High output Cardiac failure and complications related to cause
- Depends on cause
3
Q
Normocytic anaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx and Sx
- Investigations
A
- Anaemia with normal MCV 80-100
- Causes:
- Decreased production of normal sized RBC = AoCD, aplastic anaemia
- Increased HbS production (sickle cell disease)
- Increased destruction of RBC - haemolysis, post-haemorrhagic anaemia
- Uncompensated increase in plasma vol (pregnancy, fluid overload
- Vit B2/B6 deficiency
- Common
- Typical of anaemia: SOB, fatigue, conjunctival pallor
- FBC - check Hb and MCV; check hx for haemorrhage
4
Q
Aplastic anaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements
- Idiopathic may be due to destruction/suppression of stem cells via AI mechanisms (>40%);
- Acquired: drugs (chloramphenicol, sulphonamides, methotrexate); Chemicals (benzene, DDT); Radiation; Viral infection (parvovirus B19); paroxysmal nocturnal haemoglobinuria
- Inherited: Fanconi’s anaemia, dyskeratosis congenita
- Annual incidence: 2-4/million; more common in males
- Can be slow onset (months) or rapid in days; anaemia syx: tiredness, lethargy and dyspnoea; thrombocytopaenia syx: easy bruising, bleeding gums, epistaxis; leukopaenia syx: increased frequency and severity of infections
- Anaemia: pallor; thrombocytopaenia: petichiae, bruises; leukopaenia: multiple bacterial and fungal infections, no hepato/splenomegaly or lymphadenopathy
- Bloods: FBC: low Hb/platelets/WCC/absent reticulocytes, normal MCV
- Blood film to exclude leukaemia (abnormal circ WBC)
- Bone marrow trephine biopsy
- Fanconi’s anaemia - increased chromosomal breakage in lymphocyte cultures in presence of DNA cross linking agents
5
Q
Disseminated intravascular coagulation
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Disorder of clotting cascade that can complicate serious illness -> 2 forms: acute overt form where bleeding and depletion of platelets and clotting factors occur AND chronic non-overt form where thromboembolism is accompanied by generalised activation of coagulation system
-
Infection (GNB sepsis esp), obs complications (missed miscarriage, severe pre-eclampsia, placental abruption, amniotic emboli), malignancy (acute promyelotic leukaemia (acute DIC) and lung/breast/GI malignancy (chronic DIC)), severe trauma/surgery, others: haemolytic transfusion reaction, burn, severe liver disease, aortic aneurysms, haemangiomas
- Pathophysiology:
- Acute DIC: endothelial damage and release of granulocyte/macrophage procoag substances leading to activation of coag; then explosive thrombin generation (depleting clotting factors and platelets, activating fibrinolytic system), bleeding in subcut tissues, skin and mucous memebranes; occlusion of blood vessels by fibrin in microcirc leads to microangiopathic haemolytic anaemia and ischaemic organ damage
- Chronic: Identical to acute DI, happens at a slower rate with time for compensatory responses which diminish the likelihood of bleeding but give rise to hypercoagulable states and thrombosis can occur
- Pathophysiology:
- Severely ill pts
- Tend to be severly unwell with syx of underlying disease; confusion, dyspnoea, evidence of bleeding
- Sx of underlying disease, fever, evidence of shock (hypotension, tachycardia);
- Acute: petichiae, purpura, ecchymoses, epistaxis, mucosal bleeding, overt haemorrhage, sx of end organ damage, resp distress, oliguria due to renal failure
- Chronic: sx of deep vein and arterial thrombosis/embolism; superficial venous thrombosis
- Bloods: FBC - low platelets/Hb/fibrinogen, high APTT/PT/fibrin degradation products/D-dimers
- Peripheral blood film: schistocytes
6
Q
Haemochromatosis
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx and Sx
- Investigations
A
- Autosomal recessive disease where increased intestinal absorption of iron causes accumulation in tissues, which may lead to organ damage
- Autosomal recessive, defect in HFE gene; genetic penetrance of haemochromatosis is complex
- Rare
- Often asyx until late stages; usually start 40-60, early: fatigue, weakness, arthropathy, ED, heart problems; may be incidental; late: DM, bronzed skin, hepatomegaly, impotence, amenorrhoea, hypogonadism, cirrhosis, cardiac - arrhythmias/cardiomyopathy, neurological/psych problems
- Haematinics: serum ferritin (high), transferrin (low), transferrin sat (high), TIBC (low); other tests to exclude: CRP (inflammation), chronic alcohol consumption, ALT (liver necrosis); LFTs; other investigations for abnormal liver fucntion, genetic testing, liver biopsy (RARE)
7
Q
Haemolytic anaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Premature erythrocyte breakdown causing shortened erythrocyte life span (<120 d) with anaemia
- Hereditary: membrane defects (hereditary spherocytosis, elliptocytosis), metabolic defects (G6PD deficiency, pyruvate kinase deficiency), haemoglobinopathies (sickle, thalassaemia)
- Acquired:
- AI: ab attach to RBC causing intra/extravascular haemolysis
- Isoimmune: transfusion reaction, haemolytic disease of the newborn
- Drugs: penicillin, quinine
- Trauma: microangiopathic haemolytic anaemia (RBC fragmentation in abnormal microcirculation) - HUS, DIC, malignant HTN
- Infection: malaria, sepsis
- Paroxysmal nocturnal haemoglobinuria
- Acquired:
- Common, genetic causes are prevalent if African, mediterranean and middle eastern popn; hereditary spherocytosis is most common inherited haemolytic anaemia in northern europe
- Jaundice, haematuria, anaemia
- Pallor, jaundice, hepatosplenomegaly
- Bloods: FBC = low Hb and haptoglobin, high reticulocytes/MCV/unconjugated bilirubin; U+Es, folate
- Blood film: leucoerythroblastic picture, macrocytosis, nucleated RBC/reticulocytes, polychromasia, may ID specific abnormal cells like: spherocytes, elliptocytes, sickle cells, schistocytes, malarial parasites
- Urine: high urobilinogen, haemoglobinuria, haemosiderinuria
- Direct coombs’ test: tests for AI haemolytic anaemia, Id RBC coated with Ab
- Osmotic fragility test or spectrin mutation analysis - Id membrane abnormalities
- Ham’s test - lysis of RBC in acidified serum in paroxysmal nocturnal haemoglobinuria
- Hb electrophoresis or enzyme assays to exclude other causes
- Bone marrow biopsy
8
Q
Haemolytic uraemic syndrome and thrombotic thrombocytopaenic purpura
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Triad of microangiopathic haemolytic anaemia, acute renal failure, thrombocytopaenia; 2 forms: D+ with diarrhoea, D- no prodromal illness identified;
- HUS overlaps with TTP which has additional features of fever, fluctuating CNS signs
- Endothelial injury results in platelet aggregation and the release of unusually large vWF multimers and activation of platelets and the clotting cascade -> small vessel thrombosis; glomerular-afferent arteriole and capillaries are particularly vulnerable, they undergo fibrinoid necrosis -> renal ischaemia and acute renal failure; promote intravascular haemolysis; Causes:
- Infection -> E. coli, shigella, neuraminidase producing infections, HIV
- Drugs -> COCP, ciclosporin, mitomicin, 5-fluorouracil
- Others -> malignant HTN, malignancy, pregnancy, SLE, scleroderma
- Uncommon, D+ HUS often affects young children; most common cause of acute renal failure in children; TTP mainly affects adult females
- GI: severe abdominal colic, watery diarrhoea that becomes bloodstained; General: malaise, fatigue, nausea, fever <38 degrees (D+); renal: oliguria/anuria, haematuria
- General: pallor, slight jaundice (haemolysis), bruising, generalise oedema, HTN, retinopathy;
- GI: abdo tenderness;
- CNS sx: occurs in TTP, weakness, reduced vision, fits, reduced consciousness
- FBC: normocytic anaemia, high neutrophils, very low platelets
- U+Es: high urea, creatinine, K+; low Na
- Clotting: normal APTT and fibrinogen levels
- LFTs: high unconjugated bilirubin, high LDH from haemolysis
- Blood cultures
- ABG: low pH, HCO3, PaCO2; normal anion gap
- Blood film: schistocytes, high reticulocytes and spherocytes
- Urine: 1+ g protein/24hrs; haematuria
- Stool samples: MC+S
- Renal biopsy: can distinguish between D+ and D- HUS
9
Q
Haemophilia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Bleeding diatheses resulting from an inherited deficiency of a clotting factor -> 3 subtypes: haemophilia A is most common F8 def, haemophilia B F9 def, haemophilia C is rare, def in F11
- Haemophilia A and B have X-linked recessive inheritance; 30% new mutations, due to inheritance patters, haemophilia mainly seen in males
- HA incidence 1/10,000 males, HB incidence 1/25,000; HC is more common in ashkenazi jews
- Syx usually begin in early childhood; swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses); painful bleeding into muscles; haematuria; excessive bruising or bleeding after surgery/trauma; female carriers usually asyx but may experience excessive bleeding after trauma
- Multiple bruises, muscle haematomas, haemarthroses, joint deformity, nerve palsies (due to nerve compression by haematomas), sx of IDA
- Clotting screen (high APTT), coagulation factor assays (low factor 8/9/11), other investigations may be performed if there are complications (arthroscopy)
10
Q
Immune thrombocytopaenic purpura
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Syndrome characterised by immune destruction of platelets resulting in bruising or a bleeding tendency
- Often idiopathic; actue ITP often seen after viral infection in children; chronic ITP is more common in adults; ITP may be associated with infections (malaria), AI (SLE, thyroid disease), malignancies, drugs (quinine); Auto Ab generated, which bind to platelet membrane proteins resulting in thrombocytopaenia
- Acute ITP presenting in children aged 2-7yrs; chronic ITP is seen in adults - 4x more common F
- Easy bruising, mucoousal bleeding, menorrhagia, epistaxis
- Visible petechiae and bruises, signs of other illness would suggest other causes
- Dx of exclusion: myelodysplasia, acute leukaemia, marrow infiltration;
- Bloods: FBC has low platelets; clotting screen: normal PT, APTT and fibrinogen; autoAb
- Blood film: to rule out pseudothrombocytopaenia
- Bone marrow: exclude other pathology
11
Q
Acute lymphoblastic leukaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts
- Lymphoblasts undergo malignancy transformation and prolif; this leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues. RF:
- Environmental (radiation, viruses)
- Genetic: down’s syndrome, neurofibromatosis type 1, fanconi’s anaemia, xeroderma pigmentosum
- Most common malignancy of childhood; peak incidence is 2-5yrs old; second peak in incidence in the elderly; annual uk incidence 1/70,000
- Bone marrow failure: anaemia, fatigue, dyspnoea, bleeding, spontaneous bruising, bleeding gums, menorrhagia, opportunistic infections
- Organ infiltration: tender bones, enlarged LN, mediastinal compression, meningeal involvement - headache, visual disturbances, nausea
- BMF: pallor, bruising, bleeding, infection; OI: lymphadenopathy, hepatosplenomegaly, CN palsies, retinal haemorrhage, papilloedema on fundoscopy, leukaemic infiltration of the anterior chamber of the eye, testicular swelling
- Bloods: FBC is normochromic normocytic anaemia, low platelets, variable WCC, high uric acid, high LDH, clotting screen
- Blood film: abundant lymphoblasts
- Bone marrow aspirate or trephine biopsy: hypercellular with >20% lymphoblasts
- Immunophenotyping: using Ab to recognise cell surface antigens
- Cytogenic - karyotyping to look for chromosomal abnormalities or translocations
- Cytochemistry
- LP: check CNS involvement
- CXR: may show mediastinal lymphadenopathy, lytic bone lesions
- Bone radiographs: mottled appearance with punched out lesions due to leukaemic infiltration
12
Q
Acute myeloblastic leukaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- MAlignancy of primitive myeloid lineage WBC with prolif in the bone marrow and blood - classified using FAB system into eight morphological variants
- Myeloblasts undergo malignant transformation and prolif; leads to replacement of normal marrow and bone marrow failure
- Most common acute leaukaemia in adults, incidence increases with age
- BMF: anaemia, lethargy, dyspnoea, bleeding due to thrombocytopaenia or DIC, opportunistic or recurrent infections
- Tissue infiltration: gum swelling or bleeding, CNS involvement - headaches, nausea, diplopia
- BMF: pallor, cardiac flow murmur, ecchymosis, bleeding, opportunistic/recurrent infections (fever, mouth ulcers, skin infections
- TI: skin rashes, gum hypertrophy, deposit of leukaemic blasts in the eye, tongue and bone (rare)
- Bloods: FBC - low Hb, low platelets, variable WCC, high uric acid, high LDH, clotting studies, fibrinogen, D-dimers
- Blood film: myeloblasts
- Bone marrow aspirate or biopsy: hypercellular with >20% blasts
- Immunophenotyping - Ab agaisnt surface Ag used to classify the lineage of the abnormal clones
- Cytogenetics
- Immunocytochemistry
13
Q
Chronic Lymphocytic leukaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Characterised by progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin; there is an overlap between CLL and NHL
- Malignant cells may accumulate as a result of their inability to undergo apoptosis; most common chromosomal changes include trisomy 12/ 11q and 13q deletions
- 90% are >50yrs, more common in males, rare in asians
- Asyx: 40-50% of cases are diagnosed following routine blood tests;
- systemic syx: lethargy, malaise, night sweats
- Syx of BMF: recurrent infections, herpes zoster infection, easy bruising or bleeding
- Non-tender lymphadenopathy, hepatomegaly, splenomegaly; late sx of BMF: pallor, cardiac flow murmur, purpura/ecchymosis
- May be associated with AI, such as haemolytic anaemia or thrombocytopaenia
- Bloods: FBC; lymphocytosis, low Hb (bone marrow infiltration, hypersplenism, autoimmune haemolysis), low platelets, low serum Ig
- Blood film: small lymphocytes with thin rims of cytoplasm, smudge cells
- Bone marrow aspirate or biopsy - lymphocytic replacement of normal marrow
- cytogenetics
14
Q
Chronic myeloid leukaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Chronic myeloblastic leukaemia is a malignant clonal disease characterised by prolif of grannulocyte precursors in the bone marrow and blood, distinguished from AML by its slower progression
- Malignant prolif of stem cells; 95% of cases have a chromosomal translocation between 9 and 22 forming philadelphia chromosome;
- variants of CML include: pH-ve CML, chronic neutrophilic leukaemia, eosinophilic leukaemia
- Pathogenesis: phil chromosomes results in the formation of BCR-ABL fusion gene; product of gene enhances tyrosine kinase activity and drives cell replication
- 3 phases of CML: relatively stable chronic phase (4-6yr duration), accelerated phase (3-9m), acute leukaemia phase - blast transformation
- Incidence increases with age; mean age of diagnosis 40-60yrs; 4x more common in males
- Asyx in 40-50% of cases; dx on routine blood count
- hypermet syx: weight loss, malaise, sweating
- BMF syx: lethargy, dyspnoea, easy bruising, epistaxis, abdo discomfort and early satiety; rare syx: gout, hyperviscosity syx (visual disturbances, headaches, priapism); may present during a blast crisis with syx of AML and ALL
- Splenomegaly - most common physical finding 90% of cases; sx of BMF: pallor, bleeding, ecchymosis
- Bloods: FBC: high WCC, low Hb, high basophils/neutrophils/eosinophils; high/normal/low platelets, high uric acid, high B12 and transcobalamin I
- Blood film: immature granulocytes
- Bone marrow aspirate or biopsy: hypercellular with raised myeloid-erythroid ratio
- Cytogenetics: show the philadelphia chromosome
15
Q
Hodgkin’s lymphoma
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Lymphoma are neoplasms of lymphoid cells, originating in the LN or other lymphoid tissues -> dx histopathologically by the presence of Reed-Sternberg Cells (binucleate lymphocytes)
- Unknown, likely env trigger in genetically susceptibile individual; EBV genome has been detected in 50% of HL
- Bimodal age distribution with peaks at 20-30yrs and >50yrs and more common in MALES
- Painless enlarging mass - most commonly in neck, also in axilla or groin - mass may become painful after alcohol ingestion
- B syx of lymphoma: fever>38 degrees, if cyclical its referred to as Pel-Ebstein fever; night sweats; weight loss >10% body weight in past 6 m
- Other: pruritis, cough, dyspnoea
- Non-tender, firm, rubbery lymphadenopathy, splenomegaly, skin excoriations, sx of intrathoracic disease (pleural effusion, SVC obstruction)
- Bloods: High ESR/CRP, FBC: anaemia of chronic disease, leucocytosis, high neutrophils, high eosinophils, lymphopaenia in advanced disease
- LN biopsy
- BM aspirate and trephine biopsy
- Imaging - CXR, CT, PET
- Ann Arbor staging:
- I=single LN region
- II= 2+ LN regions on one side of diaphragm
- III= LN regions on both sides of the diaphragm
- IV =extranodal involvement
- A = absence of B syx
- B= presence of B syx
- E= localised extranodal extension
- S = involvement of spleen
16
Q
Non-hodgkin’s lymphoma
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Lymphomas are malignancies of lymphoid cells originating in LN or lymphoid tissues -> 85% B cell, 15% T cell and NK cell forms; range from stable, indolent disease to aggressive disease
- Complex process involving accumulation of multiple genetic lesions; changes in the genome in certain lymphoma subtypes have been associated with the introouction of foreign genes via oncogenic viruses
- RF: Rt, immunosuppressive agents, chemo, HIV, HBV, HCV, connective tissue disease
- Incidence increases with age, more common in MALES and in western world
- Painless enlarging mass (neck, axilla, groin);
- systemic syx: fever, night sweats, weight loss >10%, syx of hyperCa
- Syx related to organ involvement: extranodal disease more common in NHL vs HL; skin rashes, headache, sore throat, abdo discomfort, testicular swelling
- Painfless firm rubbery lymphadenopathy, skin rashes: mycosis fungoides; abdo mass, hepatosplenomegaly
- Sx of bone marrow involvement: anaemia, infections, purpura
- Bloods: FBC - anaemia, neutropaenia, thrombocytopaenia; high ESR/CRP, Ca may be raised, HIV/HBV/HCV serology
- Blood film - lymphoma cells may be visible in some pts
- Bone marrow aspiration and biopsy
- Imaging - CXR, CT, PET
- LN biopsy - allows histopathological evaluation, immunophenotyping and cytogenetics
- Staging: Ann-Arbor
17
Q
Multiple myeloma
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Haematological malignancy characterised by prolif of plasma cells, resulting in bone lesions and the production of monoclonal immunoglobulin
- Unknown; possible viral trigger; chromosomal aberration are frequent, associated with ionising radiation, agricultural work or occupational chemical exposures
- Annual incidence - 4/100,000; peak incidence 70yrs; afro caribbean > white > asians
- Incidental finding on blood tests; bone pain (back and ribs, sudden and severe caused by pathological fracture)
- Infections - often recurrent
- General - tiredness, thirst, polyuria, nausea, constipation, mental change (due to hyperCa)
- Hyperviscosity - bleeding, headaches, visual disturbance
- Pallor, tachycardia, flow murmur, sx of HF, dehydration, purpura, hepatosplenomegaly, macroglossia, carpal tunnel, peripheral neuropathies
- Bloods: High ESR/?CRP; U+E - high creatinine, high Ca; normal ALP; FBC - low Hb, normochromic, normocytic
- Blood film: rouleaux formation with high protein
- Serum/urine electrophoresis - serum paraprotein, Bence-Jones protein
- Bone marrow aspirate and trephine - high plasma cells
- Chest, pelvic or vertebral XR - osteolytic lesions with surrounding sclerosis, pathological fractures
18
Q
Myelodysplasia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Series of haematological conditions characterised by chronic cytopaenia (anaemia, neutropaenia, thrombocytopaenia) and abnormal cell maturation -> 5 subgroups:
- Refractory anaemia
- RA with ringed sideroblasts
- RA with excess blasts
- Chronic myelomonocytic leukaemia
- RAEB in transformation
- May be primary ; arise in pts who received chemo/RT for previous malignancies; may have chromosomal abnormalities
- Mean age of dx 65-75; more common in males and 2x as common as AML
- May be asyx and dx on routine blood counts;
- syx of BM failure: anaemia (fatigue and dizziness), neutropaenia (recurrent infections), thrombocytopaenia (easy bruising, epistaxis)
- RF: occupational exposure to toxic chemicals, prior chemo/radiotherapy
- BMF: Anaemia (pallor, cardiac flow murmur), neutropaenia (infections), thrombocytopaenia (purpura, ecchymoses), gum hypertrophy, lymphadenopathy, spleen NOT enlarged
- Bloods - FBC in pancytopaenia
- Blood film: normo/macrocytic red cells; variable microcytic red cell in RARS, low granulocytes, granulocytes are not granulated, high monocytes in CMML
- Bone marrow aspire or biopsy: hypercellularity, ringed sideroblasts (haemosiderin deposits in the mitochondria of erythroid precursors forming an apparent ring around the nucleus; abnormal granulocyte precursors, 10% show marrow fibrosis
19
Q
Myelofibrosis
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis in associeted with extramedullary haematopoiesis and splenomegaly
- Pathogenesis: abnormal megakaryocytes release cytokines that stimulate fibroblast prolif and collagen depostion in bone marrow; results in extramedullary haematopoiesis in spleen and liver
- 1ry stem cell defect is unknown; it results in increased numbers of abnormal megakaryocytes with stromal prolif 2ry to growth factors released by megakaryocytes with stromal prolif 2ry to growth factors released by megakaryocytes; 30% of patients have a previous hx of polycythaemia rubra vera or essential thrombocythaemia
- Rare, peak onset: 50-70yrs
- Asyx dx after routine blood count; systemic syx: common - weight loss, anorexia, fever, night sweats, pruritis
- Uncommon - LUQ pain, indigestion, bleeding, bone pain, gout
- Splenomegaly, hepatomegaly in 50-60%
- Bloods: FBC: initially variable Hb, WCC and platelets; later stages -> anaemia, leukopaenia, thrombocytopaenia; LFTs are abnormal
- Blood film: leucoerythroblastic changes, tear drop poikilocyte red cells
- Bone marrow aspirate or biopsy: Aspiration usually unsuccessful - dry tap, trephrine biopsy shows fibrotic hypercellular marrow with dense reticulin fibres on silver staining
20
Q
Polycythaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Increase in Hb conc above the upper limit of normal for a person’s age and sex -> relative Pc (normal RBC mass but low plasma vol), absolute Pc (increased RBC mass)
- Pc Rubra Vera - cloncal prolif of myeloid cells; varied morphological maturity and haematopoietic efficiency, mutations in JAK2 tyrK are involved
- 2ry Pc ->appropriate incease in EPO: due to chronic hypoxia, so upreg of EPO
- inappropriate increae in EPO: renal (carcinoma, cysts, hydronephrosis), hepatocellular carcinoma, fibroids, cerebellar haemangioblastoma, 2ry pc due to EPO abuse in athletes
- Relative Pc -> dehydration (diuretics, burns, enteropathy); gaisbock’s syndrome - occurs in young male smokers with HTN which results in a decrease in plasma volume and an apparent increase in red cell count
- 2ry Pc ->appropriate incease in EPO: due to chronic hypoxia, so upreg of EPO
- Annual UK incidence 1.5/100,000; peak age 45-60yrs
- Headaches, dyspnoea, tinnitus, blurred vision, pruritis after hot bath, night sweats, thrombosis (DVT/stroke), pain from peptic ulcer disease, angina, gout, choreiform movements
- Plethoric complexion (red, ruddy), scratch marks from itching, conjunctival suffusion, retinal venous engorgement, HTN, splenomegaly, sx of underlying aetiology in 2ry pc
- For Dx: FBC: high Hb, Hct, low MCV;
- isotope dilution techniques: allows confirmation of plasma volume and red cell mass, distinguishes between relative and absolute pc
- Pc rubra vera: high WCC, hgih platelets, low serum EPO, JAK2 mutation, bone marrow trephine and biopsy shows erythroid hyperplasia and raised megakaryocytes
- 2ry pc: high serum EPO, exclude chronic lung disease/hypoxia, check for EPO secreting tumours
21
Q
Sickle cell disease
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
- Management
- Complications
- Prognosis
A
- Chronic condition with sickling of RBC caused by inheritance of HbS
- Sickle cell anaemia
- Sickle cell trait
- Sickle cell disease -> HbS and HbC and Beta thalassaemia
- Autosomal recessive; caused by point mutation in the beta globin gene substituting glutamic acid in postion 6 by valine, resulting in abnormal hbS, deO2 of HbS alters the conformation resulting in sickling of red cells, making them more fragile and inflexible; sickled red cells prone to: sequestration and destruction, occlusion of small blood vessels causing hypoxia
- Precipitation of sickling due to: infection, dehydration, hypoxia, acidosis
- Rarely presents before 4-6m; common in Africa, caribbean, middle east and other areas with a high prevalence of malaria
- x
- Syx secondary to vaso-occlusion or infarction ->
- autosplenectomy (splenic atrophy or infarction) - leads to increased risk of infections with encapsulated organisms;
- abdo pain;
- bones -> painful crises affect small bones of the hands and feet causing dactylitis in children, painful crises mainly affect the ribs, spine, pelvis and long bones in adults
- Myalgia and arthralgia
- CNS - fits and strokes
- Retina - visual loss (prolif retinopathy)
- Syx of sequestration crisis - due to pooling of red cells in various organs
- Liver -> exacerbation of anaemia
- Lungs -> acute chest syndrome - SOB, cough, pain, fever
- Corpora cavernosa -> persistent erection, impotence
- Syx secondary to vaso-occlusion or infarction ->
- x
- Sx of 2ry to vaso-occlusion, ischaemia, infarction:
- Bone - joint or muscle tenderness or swelling due to avascular necrosis
- Short digits - due to infarction in small bones of the hands
- Retina - cotton wool spots due to retinal ischaemia
- Sx 2ry to sequestration crises:
- Organomegaly: spleen is enlarged in early disease, spleen will reduce in size due to splenic atrophy
- Priapism
- Sx of anaemia
- Sx of 2ry to vaso-occlusion, ischaemia, infarction:
- Bloods: FBC - low Hb, reticulocytes: high in haemolytic crises, low in anaplastic crises, U+Es
- Blood film: sickle cells, anisocytosis, features of hyposplenism: target cells, howell-jolly bodies
- Sickle solubility test: dithionate is added to blood, increased turbidity
- Hb electrophoresis - shows HbS, absence of HbA, high HbF
- Hip XR: femoral head is common site of avascular necrosis
- MRI/CT head: neurological complications
- Acute (painful crises) -> O2, IV fluids, strong analgesia (IV opiates), Abx;
- Infection prophylaxis: penicillin V, regular vaccinations
- Folic acid: severe haemolysis or in pregnancy
- Hydroxyurea/carbamide: increases HbF levels, reduces the frequency and duration of sickle cell crisis
- Red cell transfusion: for severe anaemia, repeated transfusions (with iron chelators), may be required in pts suffering from repeated crises
- Advice: avoid precipitating factors, good hygeine and nutrition, genetic counselling, prenatal screening
- Surgical: bone marrow transplantation; joint replacement in cases with avascular necrosis
- Aplastic crises: infection with parvovirus B19 can lead to temp cessation of erythropoiesis; haemolytic crises, pigment gallstones, cholecystitis, renal papillary necrosis, leg ulcers, cardiomyopathy
- Survival until around the age of 50yrs; mortality usually results of: pulm or neuro complications in adults; infection in children
22
Q
Thalassaemia
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Group of genetic disorders, characterised by reduced globin chain synthesis
- Autosomal recessive; result in imbalance of globin chain production and deposition in RBC and erythroblasts -> leads to: ineffective erythropoiesis, haemolysis, anaemia, extramedullary haematopoiesis
- Alpha thalassaemia: reduction in alpha-globin chain synthesis, 4 genes on chromosome ->
- 4 gene deletions = HbB hydrops fetalis;
- 3 gene = HbH, microcytic hypochromic anaemia and splenomegaly;
- 2 gene = alpha 0 thalassaemia, microcytic hypochromic red cells, no anaemia
- 1 gene = alpha+ thalassaemia, microcytic hypochromic red cells, No anaemia
- Beta thalassaemia:
- Major: little or no beta chain synth
- Intermedia: mild defect in beta chain synthesis leading to: microcytic anaemia, reduced alpha chain synthesis, increased gamma chain synthesis
- Trait: (heterozygous carrier state) -> asyx, mild microcytic anaemia, increased red cell count
- Alpha thalassaemia: reduction in alpha-globin chain synthesis, 4 genes on chromosome ->
- Worldwide, most common in mediterranean and areas of the middle east
- Major: anaemia, presenting at 3-6m, failure to thrive, prone to infection
- alpha/beta thalassaemia trait -> asyx, detected during routine blood tests or due to FHx
- Major: pallor, malaise, dyspnoea, mild jaundice, frontal bossing, thalassaemia fascies, hepatosplenomegaly, pts with intermedia might have these
- Bloods: FBC - low Hb, low MCV, low MCH
- Blood film: hypochromic microcytic anaemia, target cells, nucleated red cells, high reticulocyte count
- Hb electrophoresis: absent or reduced HbA, high hbF
- Bone marrow: hypercellular, erythroid hyperplasia
- Genetic testing
- Skull XR - hair on end appearance in beta thalassaemia major, caused by expansion of marrow into cortex
23
Q
Vitamin B12 deficiency
- Definition
- Aetiology/risk factors
- Epidemiology
- Presenting Syx
- Presenting Sx
- Investigations
A
- Having insufficient vit B12 to meet demands
- B12 found in meat and animal protein foods; absoprtion occurs in terminal iluem and required IF; pernicious anaemia is AI condition, involving gastritis, atrophy of all layers of the body and fundus of stomach and loss of normal gastric glands, parietal and chief cells, leads to lack of IF; other causes:
- Gastric - gastrectomy, atrophic gastritis
- Inadequate intake
- Intestinal - malabsorption, ileal resection, crohns affecting terminal ileum, tropical sprue
- Drugs - colchicine, metformin
- Peak age 60yrs; vegans have higher risk of dietary vit B12 deficiency
- Typical anaemia syx, fatigue, lethargy, dyspnoea, faintness, palpitations, headache, neuro: paraesthesia, numbness, cognitive changes, visual disturbances
- Pallor, HF (severe anaemia), glossitis, angular stomatitis, neuropsych: irritability, dementia, depression; neuro: subacute combined degeneration of spinal cord, peripheral neuropathy
- Serum B12 is not very accurate/reliable, other new tests: plasma total homocysteine, plasma methylmalonic acid, holotranscobalamin
- FBC and blood film: hyperegmented neutrophils, oval macrocytes, circulating megaloblasts
- Pernicious anaemia tests: anti-IF Ab, anti-parietal cell Ab, schilling test
24
Q
von Willebrand disease
- Definition
- Aetiology/risk factors
- Presenting Syx and Sx
- Investigations
A
- Bleeding disorder which may present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after trauma and easy bruising -> 3 types:
- vWF works well but not enough of it
- normal vWF levels but abnormal so doesn’t function correctly
- No vWF
- Caused by abnormality in the expression/function of vWF, usually autosomal dominant; vWF is an adhesive bridge between platelets and the damaged subendothelial collagen; vWF also binds to factor VIII and prevents its degradation
- Easy bruising, epistaxis - hard to stop, prolonged bleeding from gums after dental procedures, heavy/prolonged menstrual bleeding, blood in stools/urine, heavy bleeding from a cut or other accident
- Bleeding time - high; APTT: high, Factor VIII - low, vWF - low, ristocetin cofactor (reduced platelet aggregation by vWF in presence of ristocetin
25
Q
Definition
Macrocytic anaemia
A
- Anaemia associated with high MCV of erythrocytes
- Megaloblastic: when bone marrow unusually large, structurally abnormal, immature red cells; deficiency of B12/folate is the cause
- Deficiency of vit B12: Reduced absorption, reduced intake (vegans), abnormal metabolism (congenital transcobalamin II deficiency)
- Deficiency of folate: reduced intake (alcoholics, elderly, anorexia), increased demand (pregnancy, lactation, malignancy), reduced absorption, jejunal disease (coeliac), drugs (phenytoin)
- Drugs: methotrexate, hydroxyurea, azathioprine, zidovudine
- NON-MEGALOBLASTIC: alcohol excess, liver disease, myelodysplasia, multiple myeloma, hypothyroidism, haemolysis, drugs
26
Q
S+S
Macrocytic anaemia
A
- Non-specific = tiredness, lethargy, dyspnoea;
- FHx of AI disease;
- previous GI surgery;
- syx of the cuase
- Anaemia: pallor, tachycardia, SOB;
- Pernicious anaemia: mild jaundice, glossitis, angular stomatitis, weight loss;
- B12 deficiency: peripheral neuropathy, ataxia, subacute combined degeneration of spinal cord, optic atrophy, dementia
27
Q
Investigations
Macrocytic anaemia
A
- Bloods: FBC: high MCV,
- pancytopaenia in megaloblastic anaemia, exclude reticulocytes;
- LFTs (high billirubin), ESR, TFT, serum vit b12, red cell folate, anti-parietal cell and anti-intrinsic factor Ab,
- serum protein electrophoresis for dense band in myeloma
- Blood film: large erythrocytes;
- megaloblastic: megaloblasts and hypersegmented neutrophil
- Schilling test: for pernicious anaemia, B12 only absorbed when given IF
- Bone marrow biopsy
- Investigations for cause
28
Q
Management
Macrocytic anaemia
A
- Pernicious anaemia: IM hydroxycobalamin for life;
- folate: oral folic acid, and if b12 def present, treated before folic acid def
29
Q
Definition
Microcytic anaemia
A
- Anaemia associated with a low MCV <80fl
- Iron deficiency - most common, caused by blood loss (GI), reduced absorption (small bowel disease), increased demands (growth, pregnancy), reduced intake (vegans)
- Anaemia of chronic disease
- Thalassaemia
- Sideroblastic anaemia - abnormality of haem synthesis, can be inherited/secondary
30
Q
S+S
Microcytic anaemia
A
- Non-specific: tiredness, lethargy, malaise, dyspnoea, pallor, exacerbation of ischaemic conditions (angina, intermittent claudication)
- Lead poisoning: can cause microcytic anaemia; anorexia, N/V, abdo pain, constipation, peripheral nerve lesions
- Anaemia: pallor, brittle nails and hair, koilonychia, glossits, angular stomatits
- Lead poisoning: blue gum line, peripheral nerve lesions, encephalopathy, convulsions, reduced consciousness
31
Q
Investigations
Microcytic anaemia
A
- Bloods: FBC (low Hb, low MCV, reticulocytes), serum irone, total iron binding capacity is high in iron def, serum ferritin (low), serum lead
- Blood film:
- IDA: microcytic, hypochromic, anisocytosis, poikilocytosis
- Sideroblastic anaemia: dimorphic blood film, hypochromic microcytic cells
- Lead poisoning: basophilic stippling
- Hb electrophoresis: for thalassaemia
- Sideroblastic anaemia: ring sideroblasts in bone marrow
- Special inv if IDA >40, male and/or post menopausal women: upper GI endoscopy, colonoscopy, haematuria
32
Q
Management
Microcytic anaemia
A
- IDA: oral iron supplements;
- sideroblastic anaemia: treat cause, pyridoxine in inherited forms, blood transfusion and iron chelation considered if no response
- Lead poisoning: remove source, dimercaprol, D-penicillinamine
33
Q
Definition
Normocytic anaemia
A
- Anaemia with normal MCV 80-100
- Causes:
- Decreased production of normal sized RBC = AoCD, aplastic anaemia
- Increased HbS production (sickle cell disease)
- Increased destruction of RBC - haemolysis, post-haemorrhagic anaemia
- Uncompensated increase in plasma vol (pregnancy, fluid overload
- Vit B2/B6 deficiency
34
Q
S+S
Normocytic anaemia
A
Typical of anaemia: SOB, fatigue, conjunctival pallor
35
Q
Investigations
Normocytic anaemia
A
FBC - check Hb and MCV; check hx for haemorrhage
36
Q
Definition
Aplastic anaemia
A
- Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements
- Idiopathic may be due to destruction/suppression of stem cells via AI mechanisms (>40%);
- Acquired: drugs (chloramphenicol, sulphonamides, methotrexate);
- Chemicals (benzene, DDT);
- Radiation; Viral infection (parvovirus B19);
- paroxysmal nocturnal haemoglobinuria
- Inherited: Fanconi’s anaemia, dyskeratosis congenita
37
Q
S+S
Aplastic anaemia
A
- Can be slow onset (months) or rapid in days;
- anaemia syx: tiredness, lethargy and dyspnoea;
- thrombocytopaenia syx: easy bruising, bleeding gums, epistaxis;
- leukopaenia syx: increased frequency and severity of infections
- Anaemia: pallor;
- thrombocytopaenia: petichiae, bruises;
- leukopaenia: multiple bacterial and fungal infections, no hepato/splenomegaly or lymphadenopathy
38
Q
Investigations
Aplastic anaemia
A
- Bloods: FBC: low Hb/platelets/WCC/absent reticulocytes, normal MCV
- Blood film to exclude leukaemia (abnormal circ WBC)
- Bone marrow trephine biopsy
- Fanconi’s anaemia - increased chromosomal breakage in lymphocyte cultures in presence of DNA cross linking agents
39
Q
Definition
Disseminated intravascular coagulation
A
- Disorder of clotting cascade that can complicate serious illness -> 2 forms:
- acute overt form where bleeding and depletion of platelets and clotting factors occur AND chronic non-overt form where thromboembolism is accompanied by generalised activation of coagulation system
- Infection (GNB sepsis esp),
- obs complications (missed miscarriage, severe pre-eclampsia, placental abruption, amniotic emboli),
- malignancy (acute promyelotic leukaemia (acute DIC) and lung/breast/GI malignancy (chronic DIC)),
- severe trauma/surgery, others: haemolytic transfusion reaction, burn, severe liver disease, aortic aneurysms, haemangiomas
- Pathophysiology:
- Acute DIC:
- endothelial damage and release of granulocyte/macrophage procoag substances leading to activation of coag;
- then explosive thrombin generation (depleting clotting factors and platelets, activating fibrinolytic system), bleeding in subcut tissues, skin and mucous memebranes;
- occlusion of blood vessels by fibrin in microcirc leads to microangiopathic haemolytic anaemia and ischaemic organ damage
- Chronic:
- Identical to acute DI, happens at a slower rate with time for compensatory responses which diminish the likelihood of bleeding but give rise to hypercoagulable states and thrombosis can occur
- Acute DIC:
