Haematology Flashcards
(116 cards)
1
Q
What is anti-phospholipid syndrome?
A
An acquired disorder characterised by a predisposition to:
1. Both venous and arterial thromboses
2. Recurrent fetal loss
3. Thrombocytopenia
2
Q
What is the aetiology of anti-phospholipid syndrome?
A
May occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
3
Q
What diseases are associated with anti-phospholipid syndrome?
A
SLE
Other autoimmune disorders
Lymphoproliferative disorders
4
Q
What are the features of anti-phospholipid syndrome?
A
- Venous/arterial thrombosis
- Recurrent fetal loss
- Lived reticularis (spasms of blood flow near the skin surface)
- Others: preeclampsia, pulmonary hypertension
5
Q
What is the pathophysiology of anti-phospholipid syndrome?
A
Antibodies against anticardiolipin and anti-beta2 glycoprotein
6
Q
What is the epidemiology of anti-phospholipid syndrome?
A
More common in young women
Accounts for 20% of strokes in < 45 years and 27% of women with more than 2 miscarriages
7
Q
What are the investigations for anti-phospholipid syndrome?
A
- Autoantibodies: anticardiolipin, anti-beta2 glycoprotein I, lupus anticoagulant
- Thombocytopenia
- Paradoxical prolonged APTT
8
Q
What is there a paradoxical rise in the APTT in anti-phospholipid syndrome?
A
Due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids in the coagulation cascade
9
Q
What is the management for anti-phospholipid syndrome?
A
- Primary thromboprophylaxis = low dose aspirin
- Secondary thromboprophylaxis:
2a: initial VTE event = lifelong warfarin with a target INR of 2-3
2b: recurrent VTE events = lifelong warfarin consider adding low dose aspirin, increase INR target to 3-4
2c: Arterial thrombosis = lifelong warfarin with a target INR of 2-3
10
Q
What is amyloidosis?
A
A (heterogenous) group of diseases characterised by extracellular deposition of insoluble amyloid fibrils
11
Q
What are the two types of amyloidosis?
A
- AL amyloid = primary, immunoglobulin light chain amyloidosis, associated with Myeloma
- AA amyloid = secondary, non-familial and familial
2a. Non- familial AA = Inflammatory polyarthropathies account for 60% of cases, then chronic infections, IBD
2b. Familial AA = familial periodic Mediterranean fever syndrome
12
Q
What are the risk factors for amyloidosis?
A
PMH of inflammatory conditions (AA)
Chronic infections (AA)
Positive FH
13
Q
What are the features of primary amyloidosis (AL)?
A
Dependent on organ involvement:
1. Kidneys: glomerular lesions—proteinuria and nephrotic syndrome
2. Heart: restrictive cardiomyopathy (looks ‘sparkling’ on echo), arrhythmias, angina
3. Nerves: peripheral and autonomic neuropathy; carpal tunnel syndrome
4. GI: macroglossia (big tongue), malabsorption/weight, perforation, haemorrhage, obstruction, and hepatomegaly
5. Vascular: purpura, especially periorbital—a characteristic feature
14
Q
What are the features of secondary non-familial amyloidosis (AA)?
A
PMH of chronic inflammation (e.g. RA/ IBD) or chronic infection (e.g. TB)
Affects the kidneys, liver, and spleen, and may present with proteinuria, nephrotic syndrome, or hepatosplenomegaly
Macroglossia is not seen; cardiac involvement is rare
15
Q
What are the appropriate investigations for amyloidosis?
A
Diagnosis made with biopsy of affected tissue: positive Congo Red staining with apple-green birefringence under polarized light microscopy
The rectum or subcutaneous fat are relatively non-invasive sites for biopsy and are positive in 80%
Can also use serum amyloid precursor (SAP) scan
16
Q
What is the management of amyloidosis?
A
AL: optimize nutrition; PO melphalan + prednisolone extends survival
High-dose IV melphalan with autologous stem cell transplantation may be better
AA: manage the underlying condition optimally
17
Q
What is the prognosis of patients with amyloidosis?
A
Median survival is 1–2 years
Patients with myeloma and amyloidosis have a shorter survival than those with myeloma alone
18
Q
What is aplastic anaemia?
A
Characterised by pancytopenia and a hypoplastic bone marrow (deficiency of all blood cell elements, no abnormal cells)
19
Q
What is the peak incidence of acquired aplastic anaemia?
A
30 years old
20
Q
What are the causes of aplastic anaemia?
A
- Idiopathic (>40%)
- Congenital: falcon anaemia
- Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin
- Toxins: benzene
- Infections: parvovirus, hepatitis
- Radiation
21
Q
What is the onset of features for aplastic anaemia?
A
Can be slow (months) or rapid (number of days)
22
Q
What are the features of aplastic anaemia?
A
Normochromic, normocytic anaemia:
1. Tiredness
2. Lethargy
3. Dyspnoea
Thrombocytopaenia:
1. Easy bruising
2. Bleeding gums
3. Epistaxis
Leukopenia:
Increased frequency and severity of infections
23
Q
What are the investigations for aplastic anaemia?
A
Bloods- FBC: 2 or more cytopenias among the following:
1. Hb < 100
2. Platelets < 50
3. Absolute neutrophil count <1.5
Reticulocyte count: low or absent
Bone marrow biopsy:
1. Hypocellular marrow with no abnormal cell population
2. Marrow space is composed mostly of fat cells and marrow stroma
Exclude other causes e.g. lymphoma, leukaemia : do a blood film
24
Q
What is the criteria for severe aplastic anaemia?
A
Marrow showing <25 % of normal cellularity
OR
Marrow showing <50 % of normal cellularity, <30% of the cells are haematopoietic plus 2 of the following:
1. neutrophils < 0.5x10⁹/L
2. platelets < 20x10⁹/L
3. reticulocytes < 40x10⁹/L
25
What is the management for aplastic anaemia?
Treat the underlying cause
If no cause, management options include:
1. Blood transfusions
2. Stem cell (bone marrow ) transplant
3. Immunosuppressants
Others: antibiotics
26
What is a blood product transfusion?
A lifesaving procedure to treat hemorrhages and to improve oxygen delivery to tissues
27
What different blood products can be transfused?
1. Packed red cells: for chronic anaemia
2. Platelet rich plasma: for patients who are thrombocytopaenic and are bleeding or require surgery
3. Platelet concentrate: for thrombocytopaenia
4. Fresh frozen plasma: used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery
5. Cryoprecipitate: Rich source of Factor VIII and fibrinogen
28
Which blood products must be cross matched?
1. Packed red cells
2. Fresh frozen plasma
3. Cryoprecipitate
4. Whole blood
(platelets can be ABO incompatible in adults)
29
What blood products are used in warfarin reversal?
1. Stop warfarin
2. Vitamin K (reversal within 4-24 hours, IV is quicker than oral)
3. Fresh frozen plasma
4. Human prothrombin complex (now first line for warfarin reversal, reversal within 1 hour)
30
What are the indications for red cell transfusions?
1. Symptomatic anemia (causing shortness of breath, dizziness, congestive heart failure, and decreased exercise tolerance)
2. Acute sickle cell crisis
3. Acute blood loss of more than 30 percent of blood volume
31
What are the indications for fresh frozen plasma transfusion?
Can be used for reversal of anticoagulant effects e.g. warfarin (but less commonly used)
32
What are the indications for platelet transfusion?
To prevent haemorrhage in patients with thrombocytopenia or platelet function defects
33
What are the indications for cryoprecipitate transfusion?
Used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy
34
How can the complications of blood product transfusions be classified?
1. Immunological: acute haemolytic, non-haemolytic febrile, allergic/ anaphylaxis
2. Infective
3. Transfusion related acute lung injury (TRALI)
4. Transfusion associated circulatory overload (TACO)
Others: hyperkalaemia, iron overload, clotting
35
What is non-haemolytic febrile reaction following a blood transfusion?
Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage
Features:
1. Fever
2. Chills
Management:
1. Stop or slow the transfusion
2. Paracetamol
3. Monitor
36
What is a minor allergic reaction following a blood transfusion?
Thought to be caused by foreign plasma proteins
Features:
1. Pruritus
2. Utricaria
Management:
1. Temporarily stop the transfusion
2. Anti-histamine
3. Monitor
37
What is an anaphylactic reaction following a blood transfusion?
Can be caused by patients with an IgA deficiency who have anti-IgA antibodies
Features:
1. Hypotension
2. Dyspnoea
3. Wheezing
4. Angioedema
Management:
1. Stop the transfusion
2. A to E approach (oxygen, fluids)
3. IM adrenaline
38
What is an acute haemolytic reaction following a blood transfusion?
ABO incompatible blood e.g. secondary to human error
Features:
1. Fever
2. Abdominal pain
3. Hypotension
Management:
1. Stop the transfusion
2. Confirm diagnosis: check blood product against patient name, send blood for Coombs test
3. Supportive care: fluid resuscitation
39
What is TACO following a blood transfusion?
Transfusion-associated circulatory overload from an excessive rate of transfusion/ pre-existing HF
Features:
1. Pulmonary oedema
2. Hypertension
Management:
1. Slow or stop transfusion
2. Consider IV loop diuretic e.g. furosemide and oxygen
40
What is TRALI following a blood transfusion?
Transfusion related acute lung injury: non-cardiogenic pulmonary oedema from increased vascular permeability
Features:
1. Hypoxia
2. Pulmonary infiltrates on chest x-ray
3. Fever
4. Hypotension
Management:
1. Stop the transfusion
2. Supportive care and oxygen
41
What transfusion reactions require stopping the transfusion ?
1. Minor allergic reaction (temporarily)
2. Anaphylaxis
3. Acute haemolytic reaction
4. TRALI
42
What is the key difference between TACO and TRALI following a blood transfusion?
TACO: hypertensive, TRALI: hypotensive
Both have pulmonary oedema but one is from circulatory overload (TACO) and one is non-cardiogenic (TRALI)
43
What is the Hb threshold to require a red blood cell transfusion?
Without ACS:
70 g/L (target for 70-90)
With ACS:
80 g/L (target for 80-100)
44
What is a bone marrow aspirate?
A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone e.g. Luekaemia, multiple myeloma, polycythaemia, bone marrow failure
45
What is haemolytic uraemic syndrome?
Generally seen in young children and produces a triad of:
1. Acute kidney injury
2. Microangiopathic haemolytic anaemia
3. Thrombocytopenia
46
What are the two types of haemolytic uraemic syndrome?
1. Primary: (less common), also known as 'atypical') is due to complement dysregulation
2. Secondary: (most cases, typical HUS)
a. Classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7
b. Pneumococcal infection
c. HIV
d. Rare: SLE, drugs, cancer
47
What is the epidemiology of haemolytic uraemic syndrome?
Shiga toxin-producing Escherichia coli (STEC) 0157:H7 is the most common cause in children, presents with diarrhoea as well
48
What are the investigations for haemolytic uraemic syndrome?
1. Full blood count:
a. Anaemia: microangiopathic hemolytic anaemia characterised by a haemoglobin level less than 8 g/dL with a negative Coomb's test
b. Thrombocytopenia
2. Fragmented blood film: schistocytes and helmet cells
3. U&E: Acute kidney injury
4. Stool culture: looking for evidence of STEC infection
5. PCR for Shiga toxins
49
What is the management of haemolytic uraemic syndrome?
1. Supportive e.g. Fluids, blood transfusion and dialysis if required
2. No role for antibiotics, despite the preceding diarrhoeal illness in many patients
3. Indications for plasma exchange in HUS are complicated:
a. General rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
4. Eculizumab (a C5 inhibitor monoclonal antibody) has evidence of greater efficiency than plasma exchange alone in the treatment of adult atypical HUS
50
What is Haemophilia?
1. An X-linked recessive disorder of coagulation
2. Haemophilia A is due to a deficiency of factor VIII (8): more common
3. Haemophilia B (Christmas disease) there is a lack of factor IX (9)
51
What are the features of Haemophilia?
1. Symptoms usually begin from early childhood
2. Haemarthroses: swollen painful joints occurring spontaneously or with minimal trauma
3. Haematomas
4. Haematuria
5. Excessive bruising or bleeding after surgery or trauma
6. Female carriers usually asymptomatic, but may have low-enough levels to cause excess bleeding after trauma, or menorrhagia and bleeding following surgery or childbirth
52
What are the investigations for Haemophilia?
1. Prolonged activated partial thromboplastin time (APTT): reflects the activity of the intrinsic and the common pathway
2. Bleeding time, thrombin time, prothrombin time normal
3. Coagulation factor assays:
a. Factor VIII and/or factor IX assay: decreased or absent factor VIII or IX levels
b. Severity is based on level of factor present
53
What is the management of Haemophilia based on?
Replacing the deficient clotting factor (up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment)
54
What is Immune thrombocytopenic purpura (ITP)?
1. An immune-mediated reduction in the platelet count
2. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex
55
What is the difference in ITP in adults and children?
1. Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination
2. In contrast, adults tend to have a more chronic condition (more commonly females)
56
How does immune thombocytopenia purpura (ITP) present?
1. May be detected incidentally following routine bloods
2. Symptomatic patients may present with:
a. petechiae, purpura
b. bleeding (e.g. epistaxis)
3. *Catastrophic bleeding (e.g. intracranial) is NOT a common presentation
57
What are the investigations for immune thrombocytopenia purpura (ITP)?
1. Full blood count: isolated thrombocytopenia
2. Blood film
3. Clotting is normal
4. In children: should be diagnosis of exclusion e.g. exclude leukaemia
58
What is the management of immune thrombocytopenia purpura (ITP)?
1. First-line treatment: oral prednisolone
2. Pooled normal human immunoglobulin (IVIG) may also be used: it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
3. Splenectomy is now less commonly used
59
What is Evan's syndrome?
ITP in association with autoimmune haemolytic anaemia (AIHA)
60
What are the cells seen in Hodgkin's lymphoma?
Reed-Sternberg cells
61
What is Macrocytic anaemia?
Anaemia associated with a high MCV of erythrocytes (>100 fl in adults)
62
What are the different causes of macrocytic anaemia?
1. Megaloblastic causes:
a. Vitamin B12 deficiency
b. Folate deficiency
2. Non-megaloblastic causes:
a. Alcohol excess
b. Liver disease
c. Hypothyroidism
d. Pregnancy
63
What is pernicious anaemia?
1. An autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency
2. Antibodies to intrinsic factor +/- gastric parietal cells
3. Anaemia plus neurological features and mild jaundice 'lemon tinge', glossitis
4. Increased risk of gastric cancer
64
What is microcytic anaemia?
Anaemia associated with low MCV (<80 fl)
65
What are the causes of microcytic anaemia?
1. Iron-deficiency anaemia
2. Thalassaemia
3. Congenital sideroblastic anaemia
4. Anaemia of chronic disease (more commonly a normocytic, normochromic picture)
5. Lead poisoning
66
What is the management of Microcytic anaemia?
1. Oral iron supplements (e.g. 200 mg ferrous sulphate tablets containing 65 mg of elemental iron, twice or thrice daily taken with food)
2. If oral iron intolerance or malabsorption, consider parenteral iron supplements (beware risk of anaphylaxis)
3. Monitor Hb and MCV, aiming for Hb rise of 1 g/dL/week
67
What are the complications of Microcytic anaemia?
High-output cardiac failure, complications of the cause
68
What is Myelodysplasia?
1. Also known as myelodysplastic syndrome (MDS)
2. An acquired neoplastic disorder of hematopoietic stem cells
3. Pre-cursor to leukaemia, may lead to AML
4. Causes low levels of one or more types of blood cells in the blood
69
What are the features of myelodysplasia?
1. More common with age
2. Presents with bone marrow failure (anaemia, neutropaenia, thrombocytopenia): depends on cell line affected
70
What is Myelofibrosis?
1. Myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
2. The resultant release of platelet derived growth factor is thought to stimulate fibroblasts
3. Haematopoiesis develops in the liver and spleen: enlarged spleen (massive)
71
What are the features of Myelofibrosis?
1. E.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
2. Massive splenomegaly
3. Hypermetabolic symptoms: weight loss, night sweats etc
72
What are the lab findings for myelofibrosis?
1. Anaemia
2. High WBC and platelet count early in the disease
3. 'tear-drop' poikilocytes on blood film
unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed
4. High urate and LDH (reflect increased cell turnover)
73
What is Normocytic anaemia?
Anaemia associated with normal MCV (80-100fl)
74
What are the causes of normocytic anaemia?
1. Anaemia of chronic disease
2. Chronic kidney disease
3. Aplastic anaemia
4. Haemolytic anaemia
5. Acute blood loss
75
What is polycythaemia?
An increase in haemoglobin (Hb) concentration above the upper limit of normal for a person’s age and sex
Classified into:
1. Relative polycythaemia (normal red cell mass but low plasma volume)
2. Absolute (true) polycythaemia (high red cell mass): polycythaemia vera
76
What are the primary and secondary causes of polycythaemia?
1. Primary: polycythaemia rubra vera
2. Secondary causes:
a. COPD
b. Altitude
c. Obstructive sleep apnoea
d. Excessive erythropoietin: cerebellar haemangioma, hypernephroma
77
What is Polycythaemia vera?
1. A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume
2. Often accompanied by overproduction of neutrophils and platelets
3. Mutation in JAK2 (95%)
4. Incidence peaks in the 60s
78
What are the features of polycythaemia vera?
1. Pruritus, typically after a hot bath
2. Splenomegaly
3. Hypertension
4. Hyperviscosity:
a. arterial thrombosis
b. venous thrombosis
5. Haemorrhage (secondary to abnormal platelet function)
6. Low ESR
79
What are the investigations for polycythaemia vera?
1. Full blood count/film:
a. raised haematocrit
b. Raised neutrophils, basophils, platelets raised in half of patients
2. JAK2 mutation
3. Serum ferritin
4. Renal and liver function tests
80
What is the diagnostic criteria for polycythaemia vera?
1. JAK2 positive: diagnosis requires both criteria to be present
A1: High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)
A2: Mutation in JAK2
2. JAK2 negative: diagnosis requires A1 + A2 + A3 + either another A or two B criteria
A1: Raised red cell mass (>25% above predicted) OR haematocrit >0.60 in men, >0.56 in women
A2: Absence of mutation in JAK2
A3: No cause of secondary erythrocytosis
A4: Palpable splenomegaly
A5: Presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cells
B1: Thrombocytosis (platelet count >450 * 109/l)
B2: Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers)
B3: Radiological evidence of splenomegaly
B4: Endogenous erythroid colonies or low serum erythropoietin
81
What is the management of polycythaemia vera?
1. Aspirin: reduces the risk of thrombotic events
2. Venesection: first-line treatment to keep the haemoglobin in the normal range
3. Chemotherapy: hydroxyurea - slight increased risk of secondary leukaemia, phosphorus-32 therapy
82
What is the prognosis of polycythaemia vera?
1. Thrombotic events are a significant cause of morbidity and mortality
2. 5-15% of patients progress to myelofibrosis
3. 5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)
83
What is sickle cell disease?
A chronic condition with sickling of red blood cells caused by inheritance of haemoglobin S (Hb S)
84
What are the different types of Sickle Cell Disease?
1. Sickle cell anaemia: Homozygosity for Hb S
2. Sickle cell trait: Carries one copy of Hb S: only symptomatic if severely hypoxic
3. Sickle cell disease: Includes compound heterozygosity for Hb S and C and for Hb S and b-thalassaemia
85
What is sickle cell anaemia?
1. An autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS
2. Symptoms in homozygotes don't tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin
86
What is the pathophysiology of sickle cell disease?
1. Normal haemoglobin: HbAA
2. Sickle cell trait: HbAS
3. Homozygous sickle cell disease: HbSS
4. Polar amino acid glutamate is substituted by non-polar valine (codon 6)
5. Decreases the water solubility of deoxy-Hb
6. In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
7. Sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction
87
What are the factors that precipitate sickling?
Infection
Dehydration
Hypoxia
Acidosis
88
What are the presenting symptoms for Sickle Cell Disease?
Symptoms secondary to vaso-occlusion or infarction:
1. Autosplenectomy (splenic atrophy or infarction): risk of infections with encapsulated organisms (e.g. pneumococcus, Haemophilus influenzae, meningococcus)
2. Abdominal pain
3. Bones: Painful crises affecting small bones of hands or feet (dactylitis) in children, and ribs, spine, pelvis and long bones in adults, chronic hip or shoulder pain (avascular necrosis)
4. Myalgia and arthralgia
5. CNS: Can cause fits or strokes (e.g. hemiplegia)
6. Retina: Visual loss (proliferative retinopathy)
Symptoms of sequestration crises (red cell pooling in various organs):
1. Such as spleen, liver (hepatosplenomegaly)
2. Exacerbation of anaemia
3. Lungs: ‘Acute chest syndrome’: breathlessness, cough, pain, fever
4. Corpora cavernosa: Persistent erection (pripiasm) and impotence
89
What is the definitive investigation for Sickle Cell Disease?
Haemoglobin electrophoresis
90
What is the management of an acute crisis in sickle cell anaemia?
1. Analgesia e.g. opiates
2. Rehydrate
3. Oxygen
4. Consider antibiotics if evidence of infection
5. Blood transfusion
6. Exchange transfusion: e.g. if neurological complications
91
What is the longer term management of sickle cell anaemia?
1. Hydroxyurea: increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
2. NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
92
What is Thalassaemia?
Group of genetic disorders characterized by reduced globin chain synthesis/ reduced production rate of either alpha or beta chains
93
What is the aetiology of Thalassaemia?
1. The autosomal recessive genetic defects result in an imbalance of globin chain production and deposition in erythroblasts and erythrocytes
2. This causes ineffective erythropoiesis (making of RBC), haemolysis, anaemia and extramedullary haemopoiesis (production of blood cells)
94
What is alpha thalassaemia?
Due to a deficiency of alpha chains in haemoglobin
95
What are the different manifestations of alpha thalassaemia (chromosome 16)?
1. If 1 or 2 alpha globulin alleles are affected then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
2. If are 3 alpha globulin alleles are affected results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
4. If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)
96
What is beta thalassaemia (chromosome 11)?
1. Major: homozygous b -thalassaemia: absence of beta globulin chains
2. Trait: heterozygous carrier
97
What are the features of beta thalassaemia major?
1. Presents in the first year of life with failure to thrive and hepatosplenomegaly
2. Microcytic anaemia
3. HbA2 & HbF raised
4. HbA absent
98
What is the management of beta thalassaemia major?
Repeated transfusion:
1. This leads to iron overload → organ failure
2. Iron chelation therapy is therefore important (e.g. desferrioxamine)
99
What is beta thalassaemia trait?
1. An autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia
2. It is usually asymptomatic
100
What are the features of beta thalassaemia trait?
1. Mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
2. HbA2 raised (> 3.5%)
101
What are the signs of Thalassaemia on physical examination?
b-Thalassaemia major:
a. Pallor
b. Malaise
c. Dyspnoea
d. Mild jaundice
e. Frontal bossing and thalassaemic facies (marrow hyperplasia)
f. Hepatosplenomegaly (erythrocyte pooling, extramedullary haemopoiesis)
Patients with b-thalassaemia intermedia may also have these signs
102
What is the definitive investigation for Thalassaemia?
Haemoglobin analysis:
1. beta-thalassaemia major: minimal to no Hb A, elevated Hb F and HbA2
2. beta-thalassaemia intermedia: decreased Hb A, elevated Hb F and HbA2
3. beta-thalassaemia trait: mostly Hb A, elevated Hb F and HbA2
103
What is Thrombotic thrombocytopenic purpura (TTP)?
Triad of:
1. microangiopathic haemolytic anaemia
2. acute renal failure
3. thrombocytopaenia
Other features include: fever and fluctuating CNS signs
104
What is the aetiology of Thrombotic thrombocytopenic purpura (TTP)?
1. Abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels
2. Deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns ('cleaves') large multimers of von Willebrand's factor
3. Overlaps with haemolytic uraemic syndrome (HUS)
105
What is the epidemiology of Thrombotic thrombocytopenic purpura (TTP)?
TTP is a rare disorder which mainly affects adult females
106
What are the features of Thrombotic thrombocytopenic purpura (TTP)?
1. Fever
2. Fluctuating neuro signs (microemboli)
3. Microangiopathic haemolytic anaemia
4. Thrombocytopenia
5. Renal failure
107
What are the causes of episodes of Thrombotic thrombocytopenic purpura (TTP)?
1. Post-infection e.g. urinary, gastrointestinal
2. Pregnancy
3. Drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
4. Tumours
5. SLE
6. HIV
108
What are the appropriate investigations for Thrombotic thrombocytopenic purpura (TTP)?
1. Bloods:
a. Platelet count: significantly low
b. Haemoglobin: normocytic anaemia
c. Haptoglobin: significantly decreased during haemolysis
2. Blood film: microangiopathic, fragmented red blood cells, raised reticulocytes, spherocytes
3. Urinalysis: renal abnormalities: proteinuria
4. U&Es: raised urea and creatinine
109
What is Von Willebrand's disease?
The most common inherited bleeding disorder, due to either a quantitative or qualitative abnormality of von Willebrand factor (VWF)
110
What is Von Willebrand factor (VWF)?
1. A plasma glycoprotein involved in blood clotting
2. Promotes platelet adhesion to damaged endothelium
3. Carrier molecule for factor VIII
111
What are the types of Von Willebrand disese?
1. Type 1: partial reduction in vWF (80% of patients)
Type 2: abnormal form of vWF
Type 3: total lack of vWF (autosomal recessive): most severe form
112
What are the presenting symptoms of Von Willebrand's disease?
1. Bleeding from minor wounds
2. FH of bleeding
3. Menorrhagia: menses associated with soaking pads within 1 hour, anaemia, decreased ferritin, and pictorial blood assessment
4. Easy and excessive bruising
5. GI bleeding
6. Epistaxis
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What are the investigations for Von Willebrand's disease?
1. Prolonged bleeding time
2. APTT: prolonged
3. Prothrombin time normal
4. Factor VIII levels may be moderately reduced (distinguish between types)
5. vWF assay: defective platelet aggregation with ristocetin
114
What is the management of Von Willebrand's disease?
1. Tranexamic acid for mild bleeding
2. Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
3. Factor VIII concentrate
115
What are hereditary haemolytic anaemia causes?
1. Membrane: hereditary spherocytosis/elliptocytosis
2. Metabolism: G6PD deficiency
3. Haemoglobinopathies: sickle cell, thalassaemia
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What are the acquired haemolytic anaemia causes?
1. Coombs positive (DAT):
a. Autoimmune: warm/cold antibody type
b. Alloimmune: transfusion reaction, haemolytic disease newborn
c. Drug: methyldopa, penicillin
2. Coombs negative:
a. Microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia
b. Prosthetic heart valves
c. Paroxysmal nocturnal haemoglobinuria
d. Infections: malaria
