Haematology P2 Flashcards
1
Q
Transfusion thresholds and targets after transfusion red blood cells:
A
transfusion threshold: -without ACS: 70g/L -with ACS: 80g/L target after transfusion: -without ACS: 70-90g/L -with ACS: 80-100g/L
2
Q
How should RBC be stored before infusion and how quickly transfused?
A
- stored at 4 degrees
- non urgent scenario, RBC transfused over 90-120 minutes
3
Q
What is cryoglobulinaemia:
A
- immunoglobulins which undergo reversible precipitation at 4 degrees
- dissolve at 37 degrees
- 1/3 idiopathic
4
Q
Type I cryoglobulinaemia:
A
- monoclonal - IgG or IgM
- associations: multiple myeloma, Waldenstrom macroglobulinaemia
5
Q
Type II cryoglobulinaemia:
A
- mixed monoclonal and polyclonal, usually with rheumatoid factor
- associations: hep C, rheumatoid arthritis, Sjogren’s, lymphoma
6
Q
Type III cryoglobulinaemia:
A
- polyclonal: usually rheumatoid factor
- associations: rheumatoid arthritis, Sjogren’s
7
Q
Symptoms cryoglobulinaemia:
A
- Raynaud’s only type I
- cutaneous: vascular purpura, distal ulceration, ulceration
- arthralgia
- renal involvement (diffuse glomerulonephritis)
8
Q
Cryoglobulinaemia tests:
A
- low complement (esp C4)
- high ESR
9
Q
Treatment of cryoglobulinaemia:
A
- immunosuppression
- plasmapheresis
10
Q
What is cryoprecipitate?
A
- blood product made from plasma (factor VIII and fibrinogen)
- usually transfuse as 6 unit pool
- indications: massive haemorrhage and uncontrolled bleeding due to haemophilia
11
Q
DIC
A
- dysregulated coagulation and fibrinolysis
- widespread clotting and bleeding
- mediated by release of TF which triggers extrinsic pathway and subsequently intrinsic pathway
- caused by sepsis, trauma, obstetric complications (HELLP), malignancy
12
Q
What is HELLP syndrome?
A
haemolysis, elevated liver function tests, low platelets
13
Q
Typical picture of DIC:
A
- low platelets
- prolonged APTT, prothrombin and bleeding time
- fibrin degradation products raised
- shistocytes due to microangiopathic haemolytic anaemia
14
Q
Factor V Leiden
A
- activated protein C resistance
- most common inherited thrombophilia
- mis-sense mutation activated by factor V is inactivated 10 times more slowly by activated protein C than normal
- hetero: 4-5 fold risk VTE
- homo: 10 fold risk VTE
- screening not recommended
15
Q
Fanconi anaemia:
A
- autosomal recessive
- haematological: aplastic anaemia, increased risk acute myeloid leukaemia
- neurological
- skeletal abnormalities: short, thumb/radius abnormalities
- cafe au lait spots
16
Q
G6PD deficiency
A
- commonest RBC enzyme defect
- Mediterranean, Africa
- x-linked recessive
- reduces NADPH and glutathione which increases red cell susceptibility to oxidative stress
- diagnose by checking levels 3 months after acute episode of haemolysis when RBCs with most severe reduced G6PD will have been haemolysed
17
Q
Features of G6PD deficiency:
A
- neonatal jaundice
- intravascular haemolysis
- gallstone
- splenomegaly
- Heinz bodies on blood film, bit and blister cells
18
Q
Drug causes of haemolysis:
A
- antimalarials: primaquine
- ciprofloxacin
- sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
19
Q
What is GVHD?
A
- multi-system complication of allogenic bone marrow transplant or solid organ transplant or transfusion in immunocompromised
- donor T cells mount immune response to host cells
- not same as transplant rejection
- poor prognosis
20
Q
Criteria for diagnosis of GVHD:
A
- transplanted tissue has immunologically functioning cells
- recipient and donor immunologically different
- recipient immunocompromised
21
Q
Acute GVHD:
A
- within 100 days of transplant
- usually affects skin, liver and GI tract
- multi-organ involvement - worse prognosis
22
Q
Chronic GVHD:
A
- following acute disease or de novo
- after 100 days post tranplante
- more varied picture: lung, eye, skin, GI
23
Q
Signs/symptoms of acute GVHD:
A
- painful maculopapular rash (often neck, palms and soles) which can progress to erythoderma or toxic epidermal necrolysis
- jaundice
- watery and blood diarrhoea
- persistent n&v
- culture negative fever
24
Q
Signs/symptoms of chronic GVHD:
A
- skin: poikiloderma, scleroderma, vitiligo, lichen planus
- eye: keratoconjunctivitis sicca, corneal ulcers, scleritis
- GI: dysphagia, odynophagia, ulceration, ileus
- lung
25
Management of GVHD:
- immunosuppression (IV steroids)
- supportive
- anti-TNF, mTOR inhibitors and extracorpeal photopheresis
26
Granulocyte colony stimulant factors:
- used to increase neutrophil count in neutropenic patients
- secondary to chemotherapy
- e.g. filgrastim, perfilgrastim
27
Causes of hereditary haemolytic anaemia:
- membrane: hereditary spherocytosis/elliptocytosis
- metabolism: G6PD deficiency
- haemoglobinopathies: sickle cell, thalassaemia
28
Causes of acquired haemolytic anaemia:
```
immune causes:
-automminue: warm/cold Ab
-alloimune: transfusion, haemolytic disease newborn
-drugs: methyldopa, penicillin
non-immune:
-microangiopathic haemolytic anaemia: TTP/HUS, DIC, malignancy, pre-eclampsia
-prosthetic valves
-paroxysmal nocturnal haemoglobinuria
-malaria
-dapsone
```
29
Haemophilia
- x-linked recessive disorder of coagulation
- A - factor VIII def
- B - factor IX def
- causes haemoarthroses, haematomas, prolonged bleeding
- prolonged APTT, normal bleeding time, thrombin time and PT
30
What is hereditary angioedema?
- autosomal dominant
- low plasma C1 inhibitor protein
- C1INH is serine protease inhibitor
- uncontrolled release of bradykinin resulting in oedema of tissue
31
Investigations in hereditary angioedema:
- C1-INH low during attack
| - low C2 and C4 (C4 most reliable and screening tool)
32
Symptoms of hereditary angioedema:
- attacks may be proceeded by painful macular rash
- painless, non-pruritic swelling of subcutaneous/submucosal tissue
- upper airways, skin or abdominal organs (occasionally abdominal pain due to visceral oedema)
- urticaria not usually feature
33
Management of hereditary angioedema:
- acute: HAE does not respond to adrenaline, antihistamines or glucocorticoids
- IV C1 inhibitor concentrate, FFP if not available
- prophylaxis: anabolic steroid Danazol
34
What is hereditary spherocytosis?
- most common hereditary haemolytic anaemia in northern european
- autosomal dominant defect of RBC cytoskeleton
- sphere shaped
- survival reduced as destroyed by spleen
35
Presentation of hereditary spherocytosis:
- failure to thrive
- jaundice, gallstones
- splenomegaly
- aplastic crisis precipitated by parvovirus infection
- degree of haemolysis variable
- MCHC elevated
36
Diagnosis of hereditary spherocytosis:
- EMA binding test and cryohaemolysis test
| - atypical presentations electrophoresis analysis of erythrocyte membranes
37
Management of acute haemolytic crisis:
- generally supportive
| - transfusion if necessary
38
Long term treatment of hereditary spherocytosis:
- folate replacement
| - splenectomy
39
Causes and features of hyposplenism:
- splenectomy
- sickle cell
- coeliac disease, dermatitis herpetiformis
- Graves'
- SLE
- amyloid
features: Howel-Jolly bodies, siderocytes
40
What is ITP?
- immune mediated reduction in platelet count
- AB against GPIIb/IIIa or Ib-V-IX complex
- children have acute thrombocytopenia that may follow infection or vaccination
- adults more chronic condition
- more common in older females
41
Presentation of ITP:
- incidentally following routine bloods
- petechiae, purpura
- bleeding
- catastrophic bleeding uncommon
42
Management of ITP:
- first line treatment for ITP is oral prednisone
| - pooled normal human Ig (IVIG) may be used
43
What is Evan's syndrome?
ITP associated with AIHA
44
Symptoms of iron deficiency anaemia:
- fatigue, SOB on exertion
- palpitations
- pallor
- nail changes (koilonychia)
- hair loss
- atrophic glossitis
- post-cricoid webs
- angular stomatitis
45
Investigations for iron deficiency anaemia:
- FBC: hypochromic microcytic anaemia
- low serum ferritin
- TIBC high
- transferrin sats low
- blodo film: anisopoikilocytosis (RBC different sizes and shapes), target cells, pencil poikilocytes
46
Management of iron deficiency anaemia:
- oral ferrous sulphate: take for 3 months after correction to replenish stores
- iron rich diet
47
ADR of iron supplementation:
- nausea
- abdo pain
- constipation
- diarrhoea
48
Iron def anaemia vs anaemia of chronic disease:
```
iron def anaemia:
-serum iron <8
-high TIBC
-low transferrin saturation
-low ferritin
anaemia of chronic disease:
-serum iron <15
-low TIBC
-low transferrin saturation
-high ferritin
```
49
What does a decrease in haptoglobin suggest?
intravascular haemolysis
50
What does an increase in MCHC suggest?
- hereditary spherocytosis
| - autoimmune haemolytic anaemia
51
What does a decrease in MCHC suggest?
mircrocytic anaemia e.g. iron deficiency
52
What does lead poisoning cause and what are the features?
```
-defective ferrochelastase
and ALA dehydrates function
-absominal pain
-peripheral neuropathy
-fatigue
-constipation
-blue lines on gum margin
```
53
Investigations with lead poisoning:
- blood lead >10mcg/dL
- microcytic anaemia
- basophilic stippling and clover leaf morphology
- sometimes raised serum and uric delta aminolaevulinic acid (distinguish from AIP)
- increased urinary coprophorphyrin
- in children, lead can accumulate in metaphysis of bones
54
Management of lead poisoning:
- dimercaptosuccinic acid (DMSA)
- D-penicillamine
- EDTA
- dimercaprol
55
Macrocytic anaemia causes:
```
megaloblastic causes:
-vit B12 def
-folate def
normoblastic causes:
-alcohol
-liver disease
-hypothyroidism
-pregnancy
-reticulocytosis
-myelodysplasia
-drugs: cytotoxics
```
56
What is MGUS?
-monoclonal gammopathy of undetermined significance
(benign paraproteinaemia and monoclonal gammopathy)
-eventually develop myeloma
57
Features of MGUS:
- usually asymptomatic
- no bone pain or increased risk of infections
- 10-30% demyelinating neuropathy
58
Differentiating features of MGUS from myeloma:
- normal immune function
- normal beta 2 microglobulin levels
- lower level of paraproteinaemia than myeloma
- stable level of paraproteinaemia
- no clinical features of myeloma e.g. lytic lesions or renal disease
59
Causes of microcytic anaemia:
- iron def anaemia
- thalassaemia
- congenital sideroblastic anaemia
- anaemia of chronic disease
- lead poisoning
60
What is myelodysplastic syndrome and what are the features:
- acquired neoplastic disorder of haematopoietic stem cells
- pre-leukaemia may progress to AML
- more common with age
- presents with bone marrow failure (anaemia, neutropenia, thrombocytopenia)
61
Myelofibrosis:
- myeloproliferative disorder
- hyperplasia of abnormal megakaryocytes
- resultant disease of platelet derived growth factor though to stimulate fibroblasts
- haematopoiesis in liver and spleen
62
Features of myelofibrosis:
- elderly with anaemia symptoms
- massive splenomegaly
- hypermetabolic symptoms: weight loss, night sweats
63
Lab findings of myelofibrosis:
- anaemia
- high WBC and platelet count early in disease
- tear drop poikilocytes on blood film
- unobtainable bone marrow biopsy (dry tap) so trephine biopsy needed
- high urate and LDH (reflect increased cell turnover)
64
What do bite and blister cells indicate:
G6PD deficiency
