Haematology Flashcards
1
Q
What is multiple myeloma?
A
-Cancer of the bone marrow plasma cells (differentiated B lymphocytes)
2
Q
What is the peak age that pts present with multiple myeloma?
A
-60-70 years
3
Q
What is the mneumonic to remember the features of multiple myeloma?
A
-CRAB >HyperCalcaemia >Renal impairment >Anaemia >Bone lesions/disease
4
Q
What are some other features (other than CRAB) that multiple myeloma may cause?
A
- Bone disease: bone pain, osteoporosis, pathological fractures
- Lethargy
- Infection
- Paraprotein production
5
Q
What are the symptoms of myeloma that pts present with?
A
-Osteolytic bone lesions cause: >back ache >pathological fractures -Hypercalcaemia >moans, groans and bones -Frequent infections -Symptoms of anaemia
6
Q
What should be checked in a pt >50 with back pain?
A
- Serum protein elctrophoresis
- ESR
7
Q
What investigations should be done for multiple myeloma?
A
- FBC
- Monoclonal proteins in serum and urine
- Bone marrow biopsy
- Blood film
- Imaging: XR, CT/MRI
8
Q
What would an FBC show in someone with multiple myeloma?
A
-Anaemia
9
Q
Which immunoglobulins would be found in a serum monoclonal proteins in someone with multiple myeloma?
A
- IgG
- IgA
10
Q
What urine monoclonal proteins would be seen in someone with multiple myeloma?
A
-Bence Jones proteins
11
Q
What would a bone marrow biopsy show in a pt with myeloma?
A
-Increase plasma cells within the bone marrow
12
Q
What would a blood film show in a pt with myeloma?
A
-Roloeaux formation
>stacking of red blood cells
13
Q
What would an xray show of someone with myeloma?
A
-Lytic ‘punched out’ lesions
>rain-drop skull
14
Q
What are the diagnostic criteria for Myeloma?
A
-One major and one minor criteria
OR
-3 minor criteria
in a pt with features of myeloma
15
Q
What are the major criteria for diagnosis of myeloma?
A
- Plasmacytoma (demonstrated on biopsy specimen)
- 30% plasma cells in bone marrow sample
- Elevated levels of myoclonal protein in blood or urine
16
Q
What are the minor criteria for myeloma diagnosis?
A
- 10-30% plasma cells in bone marrow sample
- Minor elevations in the level of monoclonal protein in blood or urine
- Osteolytic lesions in imaigng
- Low level of antibodies in blood
17
Q
What are some poor prognostic features of myeloma?
A
- > 2 osteolytic lesions
- Beta-2 macroglobulin >5.5mg/L
- Hb <11g/L
- Albumin <30g/L
18
Q
What are the principles of management for myeloma?
A
-Treat symptomatic pts only
19
Q
How are asymptomatic myeloma pts managed?
A
-regular monitoring
20
Q
How is symptomatic myeloma managed?
A
- Stem cell transplant
- Intensive drug treatment (chemo)
21
Q
What chemo regimes are used to treat symptomatic myeloma?
A
-Thalidomaide or bortezomib with dexamethasone
> supportive treatment: analgesia, bisphosphonates, blood transfusions
22
Q
Which pts are considered candidates for a stem cell transplant?
A
- Pts under 65 of fit pts under 70
- Assess general fitness, diagnosis, stage of disease
- Younger and physically fitter people do better
23
Q
What is monoclonaL gammopathy of undetermined significance?
A
-Also known as benign paraporteinaemia and monoclonal gammopathy
>10% develop myeloma at 5 years
>50% develop myeloma at 15 years
24
Q
What are the features of MGUS?
A
- Usually asymptomatic
- 10-30% of pts have demyelinating neuropathy
25
How can MGUS be differentiated from myeloma?
- Normal immune function
- Normal beta-2 macroglobulin levels
- Lower level or paraproteinemia than myleoma
- Stable level of paraproteinaemia
- No clinical features of myeloma
26
What is lymphoma?
-Malignant proliferation of lymphocytes
>accumulate in lymph nodes and cause lymphadenopathy
>can be found in the peripheral blood or other organs (bone marrow, spleen)
27
What are the different type of lymphoma?
- Hodgkin's
| - Non-Hodgkins
28
What are the causes of lymphoma?
- Most cases unknown
- Infection
- Primary immunodeficiency
- Secondary immune deficiency ie HIV, transplant pts
- Autoimmune disorders
29
What are some examples of infections that cause lymphoma?
- EBV
- HTLV-1
- Helicobacter pylori
30
What are the symptoms of Hodgkin's lymphoma?
- Enlarged, painless, non-tender, 'rubbery' superficial lymph nodes
- Asymmetrical
- Usually cervical but can be axillary or inguinal
- May fluctuate in size
- Alcohol induced lymph node pain
31
What are the constitutional B symptoms that present with Hodgkin's lymphoma?
- Pel-Ebstein fever (rises abruptly, stays high for a week and then drops for a week)
- Weight loss
- Night sweats
- Pruritus
- Lethargy
32
When does Hodgkin's lymphoma typically present?
-3rd and 7th decade
33
What are the signs of Hodgkin's lymphoma?
- Painless lymphadenopathy
- Normocytic anaemia, eosinophillia, raised LDH on blood tests
- Hepatosplenomegaly
- Cachexia
34
What investigations should be done for lymphoma?
- Lymph node biopsy
- Imaging (for staging)
- Bloods: FBC, film, LFT, LDH
- Immunophenotyping
35
What blood test results would indicated a poorer prognosis in someone with lymphoma?
- Raised ESR
- Low HB
- Raised LDH due to increased cell turnover
36
What is the histiological cell type associated with Hodgkin's lymphoma?
-Reed-Sternberg cells
| >mirror image nuclei appearance
37
What is the gold standard diagnosis for Hodgkin's lymphoma?
-Excision of a complete Lymph node - submitted for detailed histiological evaluation
38
What staging system is used to classify lymphoma?
-Ann Arbor classification
39
What are the stages of Ann Arbor classification?
-Stage 1 = confined to one lymph node region
-Stage 2 = confined to 2 or more lymph node regions on the same side of the diaphragm
-Stage 3 = affecting lymph node regions on both sides of the diaphragm
-Stage 4 = spread beyond lymph nodes (e.g. liver, bone marrow)
*Each stage is then split further into
A – no systemic symptoms other than pruritis
B – B symptoms present - weight loss, fever, night sweats
40
What are the 4 subtypes of Hodgkin's lymphoma?
- Nodular sclerosing Hodgkin lymphoma (most common)
- Mixed cellularity Hodgkin lymphoma
- Lymphocyte depleted Hodgkin lymphoma (worst prognosis)
- Lymphocyte rich classical hodgkin lymphoma (best prognosis)
41
What are poor prognostic factors for lymphoma?
- Male sex
- Increasing age
- Stage 4 disease
42
How is Hodgkin's lymphoma treated?
- Stage 1-2A: short course combination chemo and radi
| - Stage 2B: 4 combination chemo
43
What drugs are used for combination chemotherapy?
```
-ABVD
>Adriamycin
-Bleomycin
-Vinblastine
-Decarbazine
```
44
What are some side effects of ABVD chemo?
- Infertility
- Doxorubicin: cardiomyopathy
- Bleomycin: lung damage
- Vinblastine: peripheral neuropathy
- Secondary cancers
- Psychological issues
45
What are some features of Non-Hodgkin's lymphoma?
- Median age: 55-60years
- Painless widespread lymphadenopathy
- Hepatosplenomegaly
- Raised LDH
- Paraproteinaemia
- Autoimmune haemolytic anaemia
- Extra-nodal disaese
46
What are the subtypes of NHL?
- Indolent or low grade NHL (follicular)
| - High grade or aggressive NHL (diffuse large B cell)
47
What are the features of indolent/low grade NHL?
- Slow growing, usually advanced at presentation
- Incurable
- Median survival 9-11 years
48
What are the features of high grade or aggressive NHL?
- Usually nodal presentation
- 1/3 cases have extranodal involvement
- Pt unwell, short history, poor prognosis
49
What are some extra-nodal features of NHL?
- Skin > cutaneous T cell lymphomas
- Oropharynx > Waldeyer's ring lymphoma (sore throat/obstructed breathing)
- Gut > gastric MALT, small bowel lymphomas
50
What is the classic treatment regime seen for NHL?
```
-R-chop
>Rituximab
>Cyclophosphamide
>Hydroxydaunorubicin
>Oncovin (vincristine
>Prednisolone
```
51
What is the role of rituximab in NHL?
- Monoclonal antibody
| - Anti- CD20
52
How does anti-CD20 work in the context of rituximab and lymphoma?
- Anti-CD20 targets CD20 on cell surgace of B cells and kills these cells by antibody-directed cytotoxicity
- Sensitises the CHOP part of R-CHOP
53
What are some poor prognostic indicators for NHL?
- Age >60
- Systemic symptoms
- Bulky disease is abdo mass >10cm
- Raised LDH
- Disseminated disease at presentation
54
What are some possible acute presentations of lymphoma?
-Infection
-SVC obstruction
>Sensation of 'fullness in the head'
>Dyspnoea
>Black outs
>Facial oedema
55
What is leukaemia?
-Malignant proliferation of haemopoietic cells
56
What are 4 types of leukaemia and which cell line do they involve?
- Acute myeloid leukaemia (AML) - cancer of myeloblasts
- Chronic myeloid leukaemia (CML) - cancer of basophils, neutrophils and eosinophils
- Acute lymphoblastic leukaemia (ALL) - cancer of lymphoblasts (precursors to B and T cells)
- Chronic lymphocytic leukaemia (CLL) - cancer of B lymphocytes
57
What is acute myeloid leukaemia?
- Clonal expansion of myeloblasts
| - Most common acute leukaemia in adults
58
What are risk factors for AML?
- Down's syndrome
- Age
- Previous chemo or exposure to radiation
- Myelodysplasia
- Myeloproliferative disorders
59
What are some examples of myeloproliferative disorders that can result in AML?
- CML
- Polycythaemia rubra vera
- Essential thrombocythaemia
- Myelofibrosis
60
What is myelofibrosis?
-Myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytes
>release of platelet derived growth factor stimulates fibroblasts = haematopoiesis develops in the liver and spleen
61
What are the features of myelofibrosis?
- Elderly person with symptoms of anaemia (usually fatigue)
- Massive splenomegaly
- Hypermetabolic symptoms ie weight loss, night sweats
62
What are the diagnostic findings of myelofibrosis?
- Anaemia
- High WBC and platelet count early in the disease
- 'Tear drop cells' on blood film
- Unobtainable marrow biosy
- High urate and LDH
63
How does AML present?
```
-Symptoms of bone marrow failure
>anaemia
>neutropenia
>thrombocytopenia
>infiltration (hepatosplenomegaly, gum hypertrophy)
>bone pain
>fever
>skin involvement
```
64
Why might WCC be high but someone with AML get frequent infections?
-There may be a high level of WCC, but number of functioning WC are low
65
What are some poor prognositc features of AML?
- >60 years
- 20% blasts after 1st course of chemo
- Cytogenetics: deletions of chromosome 5 and 7
66
How can AML be classified?
-French-American-British classification
67
What is acute pre-myelocytic leukaemia?
- Associated with t(15;17)
- Fusion of PML and RAR-alpha genes
- Presents younger that other types of AML
- Good prognosis
68
What type of cells are seen in someone with acute pre-myelocytic leukaemia?
- Auer rods
| - Seen with myeloperoxidase stain
69
How does pre-myelocytic leukaemia present?
-DIC/thrombocytopenia
70
How is AML treated?
- Supportive therapy
- Chemotherapy: daunorubicin, cytarbine
- Allogenic bone marrow Transplantation (with cyclophosphamide to kill all leukaemic cells pre-transplant)
71
Which drugs are used to prevent graft vs host disease post transplant in someone with AML?
-Cyclosporin and methotrexate
72
What is chronic myeloid leukaemia?
- Uncontrolled clonal proliferation of myeloid cells
- Presents between 60-70 years
- Slight male predominance
- Slow onset
73
What causes CML?
-associated with the PHILADELPHIA CHROMOSOME
>t(9:22)
-Those without philadelphia chromosome have worse prognosis
74
How does CML present?
```
-Mostly chronic and insidious. Some detected incidentally
>Weight loss
>Tiredness
>Fever and sweats
>Bleeding
>Abdo discomfort (splenomegaly)
>gout (purine breakdown)
```
75
What investigations should be done for CML?
- Raised WCC
- Decreased or normal Hb
- Variable platelets
- Urate increased
- B12 increased
- Bone marrow biopsy (hypercellular)
- Cytogenic analysis of blood or bone marrow showing Ph Chromosome
76
How is CML treated?
- IMATINIB (tyrosine kinase inhibitor)
- Hydroxycarbamide
- Interferon-alpha
- Allogenic bone marrow transplant
77
What are the phases of CML?
- Chronic: lasting months/years, few/no symptoms
- Accelerated phase: increase in symptoms, spleen size, difficulty controlling blood cell counts
- Blast transformation: features of acute leukaemia and death
78
What is the prognosis of CML?
-Survival >90% at 5 years
79
What is the epidemiology and aetiology of acute lymphoblastic leukaeamia?
- Most common malignancy affecting children
- Peak incidence 2-5 years
- Boys affected> girls
- Genetic susceptibility and environmental triggers
- CNS involvement is common
80
What are the risk factors/assocaitions with ALL?
- Down's syndrome
| - Ionising radiation ie xrays during pregnancy
81
What are the types of ALL?
- Common ALL (75%) - CD10 present, pre-B phenotype
- T cell (20%)
- B-cell (5%)
82
What are the features of ALL?
```
-Bone marrow failure features:
>anaemia
>neutropenia
>thrombocytopenia
-Other
>bone pain (2ndry to bone marrow infiltration)
>Hepatosplenomegaly
>Lymphadenopathy
>Testicular swelling
>Neurological (cranial nerve palsies, meningism)
```
83
What are some of the common and severe infections seen in children with ALL?
- Chest: PCP
- Mouth: candidiasis
- Perianal
- Skin infections
- Bacterial septicaemia
- Zoster, measles, CMV
84
What tests are done for ALL?
- Blood film and bone marrow biopsy (shows blast cells)
- WCC - v high
- CRX/CT: mediatsinal and abdo LN involvement
- LP: for CNS involvement
85
How is ALL treated?
- Supportive
- Infection management
- Chemotherapy
- Matched related allogenic marrow transplants
86
What kind of supportive therapy is given to someone with ALL?
- Blood/platelet transufsion
- IV fluids
- Allopurinol (prevents tumour lysis syndrome)
- Hickman line for IV access
87
What infection management is given to someone with ALL?
- Immediate IV abx
- Antifungals
- Antivirals
- Antifungals
- Co-trimoxazole for PCP
88
What are some poor prognostic factors for ALL?
- Age <2 or >10
- WCC >20 at diagnosis
- T or B cell surface markers
- Non-Caucasians
- Male sex
- Philadelphia chromosome present
89
Which features in a person aged 0-24 should prompt a very urgent (within 48hrs) FBC to investigate for leukaemia?
- Pallor
- Persistent fatigue
- Unexplained fever
- Unexplained persistent infections
- Generalised lymphadenopathy
- Persistent or unexplained bone pain
- Unexplained bruising
- Unexplained bleeding
90
When should someone between 0-24 years be referred urgently for assessment for leukaemia?
- Unexplained petechiae
| - Hepatosplenomegaly
91
What is chronic lymphocytic leukaemia?
- Most common leukaemia
- Grandual accumulation of B lymhocytes in the blood, BM, spleen and LN
- Often incidental finding on FBC, can be anaemic or infection prone
- If severe: weight loss, sweats, anorexia
92
How is CLL more likely to affect?
- Elderly
| - Males
93
What are the features or CLL?
- Often none
- Constiutional: anorexa, weight loss
- Bleeding + infections
- Lymphadenopathy more marked than in CML
94
What is the clinical course of CLL?
-Variable
-Progressive lymphadenopthy and hepatosplenomegaly
-Autoimmune features ie haemolysis, ITP
-Bone marrow failure
>hypogammaglobulinaemia + infection
-Death often due to infection
95
Which infections are commonly associated with mortality in someone with CLL?
- Pneumococcus
- Haemophilus
- Meningococcus
- Candida
- Aspergillus
96
What investgations are done to diagnose CLL?
- Blood film: smudge cells
| - Immunophenotyping
97
What are complications of CLL?
- Hypogammaglobulinaemia > recurrent infections
- Warm autoimmune haemolytic anaemia
- Transformation to high-grade lymphoma (richter's transformation)
98
What is Richter's transformation?
- Occurs when leukaemia cells enter the lymph node and change into high-grade, fast growing non-Hodgkin's lymphoma
- Pt suddenly becomes very unwell
99
What are the symptoms of Richter's transformation?
- Lymph node swelling
- Fever without infection
- Weight loss
- Night sweats
- Nausea
- Abdominal pain
100
How is CLL staged?
-Binet staging
>A: lymphocytosis +/- 3 nodal areas
>B: 3 + nodal areas
>C: anaemia and/or thrombocytopenia
101
How is CLL treated?
- Do nothing
- Chemotherapy
- Monoclonal antibodies ie anti-CD20 rituximab
- Targeted therapy
- Bone marrow transplant
- Supportive care ie transfusions, IVIG for recurrent infections
102
What is the prognosis of CLL?
- 1/3 never progress
- 1/3 progress slowly
- 1/3 progress actively
103
What's the difference between autologous and allogenic stem cell transplants?
- Autologous: enables escalation of chemo with stem cell 'rescue'
- Allogenic: More toxic, stem cells attack residual tumour and recipient. - can cause graft vs host disease
104
What is the appearance of Burkitt lymphoma on lymph node biopsy?
-Starry sky appearance
105
What is burkitt lymphoma?
- Rapidly proliferating B cell tumour
- Can present in weird ways due to rapid proliferation ie nerve root compression
- Ass. w/ EBV
106
What is Waldernstrom's macroglobulinaemia?
- Uncommon condition seen in older men
- Lympholpasmacytoid malignancy characterised by secretion of a monoclonal IgM paraprotein
- Paraproteinaemia cause hyperviscosity of blood = ^ risk of ischaemic stroke
107
What are the features of Waldenstom's macroglobulinaemia?
- Monoclonal IgM paraproteinaemia
- Systemic upset
- Hyperviscosity syndrome: visual disturbance, stroke, headahcehes, spont. bleeding from mucus membranes
- Hepatosplenomegaly
- Lymphadenopathy
- Cyroglobulinaema (Raynaud's)
108
Define anaemia
- Low hb concentration
| - >either due to a low red cell mass or increased plasma volume ie in pregnancy
109
What are the normal values of Hb in men and women?
-Males: 13.1-16.6g/dl
>low Hb <135g/L
-Females: 11-14.7g/dl
>Low Hb < 115g?L
110
What are the symptoms of anaemia?
- Fatigue
- Dyspnoea
- Faint
- Palpitations
- Headaches
- Tinnitus
- Anorexia
- Angina
111
What are the signs of anaemia?
-Pallor: conjunctiva, palmar creases
-Hyperdynamic circulation in severe anaemia:
>Tachycardia
>Flow murmur
>Cardiac enlargement
>retinal haemorrhage
>Heart failure (rare)
112
What are the causes of microcytic anaemia?
- Iron deficiency
- Thalassaemia (reduced/faulty
- Chronic disease (normally normocytic)
- Lead poisoning
113
What is iron deficiency anaemia?
- Microcytic anaemia due to lack of iron
- Common
- Seen in 14% of menstruating women
114
What ar ethe causes of iron deficiency anaemia?
- Blood loss
- Insufficient dietary intake
- Malabsorption ie Coeliac disease
115
What are the signs of Iron deficiency anaemia?
- Kolionychia (spoon shaped nails)
- Atrophic glossitis (big red tongue)
- Angular stomatitis (sores/ulceration in corner of mouth)
- Post-cricoid webs (Plummer vision syndrome)
116
What is seen on a blood film for Iron deficiency anaemia?
- Target cells
- Pencil poikilocytes
- If combines with B12/folate deficiency - dimorphic film occurs with mixed micro and macrocyctic cells
117
How is iron deficiency anaemia treated?
- Treat the cause: oral iron ie ferrous sulphate
- Continue until Hb is normal + for at least 3/12 to replenish stores
- Iron deficiency with no obvious source of bleeding = careful GI workup
118
What are the side effects of ferrous sulphate?
- Nausea
- Abdominal pain
- Diarrhoea or constipation
- Black stools
119
What is anaemia of chronic disease?
```
-Most common cause of anaemia in hospital pts
>Chronic infection
>Vasculitis
>RA
>Malignancy
>Renal failure
```
120
What investigation results will be seen for anaemia of chronic disease?
- Normocytic anaemia
- Ferritin normal or raised
- Check haemoatinics as causes of chronic anaemia are usually multifactoral
121
How is anaemia of chronic disease treated?
- Treat underlying disaese vigorously - achieve optimum therapy
- EPO: effective at raising Hb level and improves QoL in cancer pt
- Iron (give parenterally)
- Hepcidin inhibitors and inflammatory modulators
122
What is sideroblastic anaemia?
- Red cells fail to completely form haem
- Leads to deposits of iron in the mitochondria that form a ring around the nucelus = sideroblast
- Congenital or acquired
- Consider when microcytic anaemia doesn't respond to iron
123
What are the causes of sideroblastic anaemia?
-Congenital
-Acquired:
>Myelodysplasia
->Alcohol
>Lead
>Anti-TB meds
124
How is sideroblastic anaemia diagnosed?
- Hypochromic microcytic anaemia
| - Bone marrow: sideroblasts and increased iron stores
125
How is sideroblastic anaemia managed?
- Supportive
- Treat any underlying cause
- Pyridoxine (vit B6) may help
- Transfusion for severe anaemia
126
What are the causes of normocytic anaemia?
- Bleeding
- Chronic disease
- Pregnancy
- Sickle cell disease
- CKD
- Haemolytic anaemia
- Aplastic anaemia
- Bone marrow failure (suspect if low WCC and platelets
- Combined haematinic deficiency
- Hypothyroidism
127
What are the causes of megalosblastic macrocytic anaemia?
- B12 deficiency
- Folate deficiency
- Cytotoxics ie hydroxycarbaminde, phenytoin
128
What are the causes of non-megaloblastic causes of macrocyctic anaemia?
- Alcohol
- Reticulocytosis
- Liver disease
- Hypothyroidism
- Pregnancy
129
What are some haematological disease causes of macrocytic anaemia?
- Myelodysplasia
- Myeloma
- Myeloproliferative disorders
- Aplastic anaemia
130
What will blood tests show for macrocytic anaemia?
-Blood film: hypersegmented polymorphs in B12 and folate deficiency
-Bone marrow biopsy
>megalobastic RBC
>Normoblastic marrow (liver disease, hypothyroid)
>Abnormal erythropoiesis (sideroblastic, leukaemia, aplasia)
>Increased erythropoiesis ie haemolysis
131
In what foods is folate found?
- Green veg
- Nuts
- Yeast
- Liver
132
What does maternal folate deficiency cause in a fetus?
-Neural tube defects
133
How is folate absorbed?
- Duodenum
| - Proximal jejunum
134
What are the causes of folate deficiency?
- Poor diet: poverty, alcoholics, elderly
- Increased demand: pregnancy, tapeworm, increased cell turnover
- Malabsorption: coeliac
- Drugs: anti-epileptics, trimethooprim, methotrexate
- Alcohol
135
What drugs cause folate deficiency?
- Anti-epileptics: phenytoin, valproate
- Trimethoprim
- Methotrexate
136
What is the role of folate in a) heart disease and b) cognition?
- a) folate lowers homocyteine levels = decreased risk of CVD
- b) benefits cognition
137
How is folate deficiency treated?
-Assess fro underlying cause
-Treat with oral folic acid (5mg/day)
-Prophylaxis in pregnancy (400mcg/day) from conception until at least 12/40
>high risk pregnany -> 5mg/day
138
Which foods have B12 in?
- Meat
- Fish
- Dairy products
139
Where is B12 absorbed?
-Binds to intrinsic factor in the stomach and complex is absorbed in the terminal ileum.
140
Why does B12 deficiency cause anaemia?
-Involved within in the synthesis of thymidine (hence DNA) = if impaired, RBC production is slow
141
What are the causes of B12 deficiency?
-Dietary (vegans)
-Malabsorption
>stomach: lack of intrinsic factor ie post gastrectomy, pernicious anaemia
>Terinal ileum: resectio, Crohn's, tapewrom
>Congenital metabolic errors
142
What are teh features of B12 deficiency?
-Normal features of anaemia
-Neuropsychiatric:
>irritability
>depressino
>psychosis
>dementia
-Neurological:
>paraesthesia
>peripheral neuropathy
>subacute degeneration of spinal cord
143
What are the features of subacute spinal cord degeneration?
- Classic triad of:
1. Extensor plantars (UMN)
2. Absent knee jerks (LMN)
3. Absent ankle jerks (LMN)
144
What is pernicious anaemia?
- Caused by an autoimmune atrophic gastritis leading to achlorhydria (absence of HCl) and lack of intrinsic factor secretion
- Usually develops in middle-old age in females
145
What are some associations with pernicious anaemia?
- Thyroid disease
- T1DM
- Addison's disease
- RA
- Vitiligo
- Hypoparathyroidism
- Predisposes to gastric carcinoma
146
What are some features of pernicious anaemia?
- Lethargy
- Weakness
- Dyspnoea
- Paraesthesia
- Mild jaundcie, diarrhoea, sore tongue
147
What are some specific investigations for pernicious anaemia?
- Parietal cell antibodies
| - Intrinsic factor antibodies
148
How is pernicious anaemia/B12 deficiency treated?
- Treat underlying cause
- B12 injections: hydroxycobalamin for malabsorption problems
- Oral B12 if definitely dietary cause
149
What is aplastic anaemia?
-Characterised by pancytopenia and hypoplastic bone marrow
150
What are the features of aplastic anaemia?
- Normochromic, normocytic anaemia
- Leukopenia with lymphocytes relatively spared
- Thrombocytopenia
- Can be presenting feature of ALL or AML
- Minority of pts develop paroxysmal nocturnal haemoaglobinuria/myelodysplasia
151
What are the causes of aplastic anaemia?
- Idiopathic
- Congenital
- Drugs
- Toxins ie benzene
- Infections ie parvovirus, hepatitis
- Radiation
152
What medications can cause aplastic anaemia?
- Phenytoin
- Cytotoxics
- Chloramphenicol
- Sulphonamides ie sulphonylureas, anticonvulsants,sulfasalazine
153
What are the hereditary causes of haemolytic anaemia?
- Membrane: hereditary spherocytosis/elliptocytocsis
- Metabolism: G6PD deficiency
- Haemoglobinopathies: sickle cell, thalassaemia
154
What are the acquired causes of haemolytic anaemia? (Immune causes)
>autoimmune
>alloimmune (transfusion reaction)
>drugs: methyldopa, penicillin
ia?
155
What are the acquired causes of haemolytic anaemia? (Non-immune causes)
```
>microangopathic:
-TTP/HUS, DIC, malignancy
>prosthetic cardiac valves
>Paroxysmal nocturnal haemaglobinuria
>Infections ie malaria
.Drugs
```
156
What is G6PD deficiency?
-Most common RBC enzyme defect?
>X-linked recessive (affecting males)
-Deficiency in G6PD causing anaemia
-Drugs, infections and fava beans can precipitate a crisis
157
What are the features of G6PD deficiency?
- Neonatal jaundice
- Intravascular haemolysis
- Gallstones
- Splenomegaly
- Heinz bodies on blood film
158
Which drugs can precipitate haemolysis in G6PD deficiency?
- Anti-malarials
- Ciprofloxacin
- Sulphonamides
- Sulphalazine
- Sulfonylureas
159
How is G6PD deficiency diagnosed?
-G6PD enzyme assay
160
What is hereditary spherocytosis?
- Most common hereditary anaemia
- Autosoma dominant
- Normal biconcave disc shape of FBC replaced by sphere-shaped one
- RBC survival reduced as destroyed by spleen
161
How does hereditary spherocytosis present?
- Failure to thrive
- Jaundice, gallstones
- Splenomegaly
- Aplastic crisis precipitated by parvovirus infection
- Spherocytes on blood film
162
How is herditary spherocytosis diagnosed?
- Osmotic fragility test
| - Spherocytes on blood film - round, lack of central pallor
163
How is hereditary spherocytosis treated?
- Folate replacement
| - Splenectomy
164
What level of iron must be reached for someone to require a blood transfusion?
- Transfusion threshold in pts without ACS - 70g/L
| - Transfusion threshold in pts with ACS - 80g/L
165
Why is the transfusion threshold lower in ACS?
-Anaemia can exacerbate ACS because there is less Hb to carry oxygen - heart has to work harder
166
What are some complications of blood transfusions?
- Immunological: acute haemolysis, allergy/anaphylaxis
- Infections
- Transfusion-related lung injury
- Fluid overload
- Hyperkalaemia
- Iron overload
- Clotting
167
What causes an acute haemolytic transfusion reaction?
- Mismatch of ABO blood group
- Causes massive intravascular haemolysis
- Symptoms begin minutes after transfusion starts: fever, abdo and chest pain, agitation and hypotension
168
What is the treatment for acute a hemolytic transfusion reaction? What are the complications?
- Immediate transfusion termination, generous fluid resus, inform lab
- Complications: DIC, renal failure
169
What causes a non-haemolytic febrile transfusion reaction?
- White blood cell HLA antibodies
| - Often the result of sensitisation by previous pregnancies/transfusions
170
What causes an allergic/anaphylactic blood transfusion reaction?
-Hypersensitivity reaction to components within the transfusion
-Symptoms arise within minutes and vary in severity:
>urticaria, anaphylaxis, hypotension, wheezing, dyspnoea, stridor
171
How is allergic/anaphylactic blood transfusion reaction treated?
- Simple urticaria: discontinue transfusion + antihistamines. Transfusion can continue when symptoms resolve
- More severe reaction: treat urgently with antihistamine, corticosteroids and bronchodilators. Permanently stop transfusion
172
Which type of infection is most likely to occur from a platelet transfusion?
-Bacterial infections
| >due to platelets being stored in room temp
173
What is the universal donor blood group for a) rbc b) FFP?
- RBC: O Rh -ve
| - FFP: AB Rh -ve
174
>2 units of blood can result in fluid overload, How can this be avoided?
-Prescribe frusemide in between transfusion of each unit
175
What are the features of post-thrombotic syndrome?
- Painful, heavy calves
- Pruritus
- Swelling
- Varicose veins
- Venous ulceration
- Management: compression stockings
176
What is the most common a) clotting disorder and b) bleeding disorder?
a) factor V leiden (activated protein C deficiency)
| b) Von Willebrand disease
177
How long should someone be on warfarin following a DVT for?
- Provoked DVT ie recent surgery: 3 months
| - Unprovoked: 6 months
178
What is the MOA for the NOACs, heparin and warfarin?
- Rivaroxiban and apixaban: direct factor Xa inhibitor
- Dabigatran: direct thrombin inhibitor (factor 2a)
- Heparin: activates antithrombin III
- Warfarin: inhibits 10,9,7,2
179
What antibiotic is recommended in an episode of neutropenic sepsis?
-Piperacillin with Tazobactam (tazocin)
180
What are the 2 main classifications of polycythaemia?
- Primary/proliferative: ie polycythaemia rubra vera
| - Secondary: reactive
181
What are some causes of secondary polycythaemia?
-Altitude
-COPD/other lung disease
-Smoking
-Cyanotic heart disease
-Obstructive sleep apnoea
-EPO/androgen excess
>cerebellar haemangioma
>hypernephroma
>hepatoma
>doping
182
What is polycythaemia rubra vera?
- Myeloporoliferative disorder (overactive bone marrow)
- Caused by clonal proliferation of marrow stem cells leading to an increased in red cell volume, often accompanied by overproduction of neutrophils and platelets
- JAK2 MUTATION
183
Which mutation is associated with polycythaemia rubra vera?
-JAK2
184
What are the features of polycythaemia vera?
- Hyperviscosity
- Thrombosis
- Pruritus (esp. after hot bath)
- Splenomegaly
- Haemorrhage
- Plethoric appearance
- Hypertension
- Gouty arthritis
185
How is polycythaemia vera investigated?
- FBC: raised haematocrit
- JAK2 mutation test
- Serum ferritin
- Renal and liver function tests
186
How is polycythaemia verta treated?
- Aspirin
- Venesection
- Bone marrow suppression (hydroxycarbamide)
187
What is sickle cell anaemia?
- Abnormal recessive disorder causing production of abnormal globin chains
- HbS produced
- Carriers are protected against Falciparum malaria
- Periods of good health with intervening crises
188
How is chronic sickle cell disease managed?
- Hydroxycarbamide to suppress bone marrow if frequent crises
- Abx and immunisation as prophylaxis for splenic infarct
- Febrile sickle cell chicken > high risk for sepsis. Give ceftriaxone
189
What is thalassaemia?
-Genetic disease of unbalanced Hb synthesis
(with underproduction or no production of one globin chain)
-Unmatched globins precipitate and damage RBC membranes causing haemolysis whilts they are still in the marrow
190
What is beta thalassaemia?
- Point mutation in the beta globin genes on chromosome 11
| - Causes decreased beta chain production (B+) or absence (Bo)
191
What investigations are done for beta thalassaemia?
- FBC + mcv (microcytic anaemia)
- Blood film
- Iron
- HbA2 and HbF raised
- Hb electrophoresis
192
How is beta thalassaemia managed?
- Promotes fitness and healthy diet
- Folate supplements
- Regular (every 2-4 weeks) transfusion to keep Hb >90
- Iron chelators to prevent iron overload (oral deferiprone)
- Large doses of ascorbic acid to increase urinary iron excretion
- Splenectomy if hypersplenism persists
- Hormonal replacement
- Genetic counselling
193
What is alpha thalassaemia?
-2 separate alpha globin genes on chromosome 16
-4 genes termed aa/aa
-Gene deletions:
>(--/--) - inutero death
>(--/-a) - moderate anaemia and features of haemolysis
>(--/aa) or (-a/-a) - asymptomatic carrier
>1 deleted: clinical state is normal
194
What are the clinical classifications of thalassaemia?
1. Thalassaemia major - transfusion dependent
2. Thalassaemia intermedia - less severe anaemia can survive without regular blood transfusions
3. Thalassaemia carrier/heterozygote - asymptomatic
195
What is beta thalassaemia trait?
- AR
- Mild hypochromic, microcytic anaemia:
- HbA2 raised (>3.5%)
- Usually aymptomatic
196
What is haemophilia?
- X linked recessive disorder or coagulation
- Up to 30% of pts have no hx of condition
- Haemophillia A - factor VIII deficiency
- Haemophillia B (christmas disease) - factor IX deficiency
197
What are the features of haemophillia?
- Haemoarthroses
- Haematomas (particular in the muscles)
- Prolonged bleeding after surgery or trauma
198
What would appear on blood tests in someone with haemophillia?
- Prolonged APTT
| - Normal bleeding time, thrombin time and prothrombin time
199
How is haemophillia treated?
- A: factor VIII replacement
| - B: factor IX replacement
200
How are platelets produced?
- Anucleate cell fragments from megakaryocytes
| - Thrombopoietin stimulates production of platelets by megakaryocytes (mainly produced in the liver)
201
What are some causes of thrombocytosis? (too many platelets)
- Reactive: platelets are an acute phase reactant
- Malignancy
- Essential thrombocytosis
- Hyposplenism (spleen breaks down platelets, so less breakdown= more platelets)
202
What is essential thrombocytosis?
- Myeloproliferative disorders
- Overlaps with CML, PRV, myelofibrosis
- Megakaryocyte proliferation results in overproduction of platelets
203
What are the features of essential thrombocytosis?
- Platelet count >600
- Thrombosis
- Haemorrhage
- Burning sensation in the hands (characteristic)
- JAK2 mutation
204
How is essential thrombocytosis managed?
- Hydroxyurea (hydroxycarbamide)
- Interferon alpha
- Low dose aspirin to reduce thrombotic risk
205
What are some causes of severe thrombocytopenia?
- ITP
- DIC
- TTP
- Haematological malignancy (marrow failure)
206
What are some causes of moderate thrombocytopenia?
- Heparin induced thrombocytopenia
- Drug induced
- Alcohol
- Liver disease
- Hypersplenism
- Viral infection (EBV, HIV, hepatitis)
- Pregnancy
- SLE/antiphospholipid syndrome
- Vit B12 deficiency
207
What is ITP?
- Immune or idiopathic thrombocytopenic purpura
- An immune mediated reduction in platelet count
- Antibodies are directed against the glycoprotein 2b/3a or Ib-V-IX complex
- Acute and chronic
- Primary and secondary
208
What are the clinical features of ITP?
-Low platelet count on bloods
-Isolated thrombocytopenia
-Non-blanching purpruirc rash
-Easy bruising
-Evidence of mucosal bleeding
>menorrhagaia
>nose bleeds
>gum bleeding when brushing teeth
209
What drugs can cause moderate thrombocytopenia?
- Aspirin
- Thiazides
- Quinine
- Diuretics
- Sulphonamides
210
What are the features of acute ITP?
- More common in children
- May follow infection or vaccination
- Usually self limiting over 1-2 weeks
211
What are the features of chronic ITP?
- More common in young/middle aged women
- Relapsing remitting course
- History of autoimmune disease
212
How is ITP managed?
- General: stop any NSAIDs or aspirin and observe platelet counts
- Prednisolone
- IVIG
- Rituximab (2nd line)
213
What is Evan's syndrome?
-ITP in association with autoimmune haemolytic anaemia
214
What is thrombotic thrombocytopenic purprua?
- Medical emergency
- Rare form of thrombotic microangiopathy
- Abnormal larege and sticking multimers of VWF cause platelet clumps in vessels
215
WHat are risk factors for thrombotic thombocytopenic purpura?
- Pregnancy/post-partum
- HIV
- Autoimmune disease
- Cancer
216
What are the features of TTP?
- Anaemia and haemolyis
- Thrombocytopenia
- Fever
- Purpura
- Cerebral dysfunction: confusion, headache, paresis, dysarthria, visual problems
217
How is TTP managed?
- No abx (can worsen outcome)
- Plasma exchange
- Steroids
- Immune suppressants
- Vincristine
218
What are the indications for a platelet transfusion?
- Platelet count <30 with clinically significant bleeding ie haematemesis, malaena, prolonged epistaxis
- Platelet count <100 for pts who have more severe bleeding classification or bleeding at critical sites ie CNS
219
What are some contra-indications for platelet transfusion?
- Chronic bone marrow failure
- Autoimmune thrombocytopenia
- Heparin induced thrombocytopenia
- Thrombotic thrombocytopenia purpura
220
What is DIC?
-Cytokine release in response to SIRS
-Causes a systemic activations of clotting cascade = microvascular thrombosis
= consumption of platelets and clotting factors which causes bleeding
-Can lead to organ failure
221
What are some causes/risk factors for DIC?
- Sepsis
- Malignancy (esp. leukaemias)
- Major trauma
- Complications of pregnancy ie abruption, pre-eclampsia)
- Incompatible blood transfusion
- Transplant rejection
- Severe liver disease
- Pancreatitis
- Recreational drugs
- Snake bites
- Connective tissue disorders
222
How is DIC investigated?
- Look for underlying cause
- Clotting profile
- D dimer: raised
- +/- evidence of organ failure
223
What would be seen on the blood tests for someone with DIC?
- Low platelets
- Prolonged PT
- Prolonged APTT
- Prolonged bleeding time
224
How is DIC managed?
-Treat underlying cause
-Supportive provision of
>platelets
>FFP
>Cyroprecipitate
225
What is Von Willebrand's disease?
-Most commonly inherited bleeding disorders
-Majority of cases are AD
-Behaves like a platelet disorder
>mucosal bleeding: epistaxis, menorrhagia
>unlikely to have large joint bleeds and muscle haematomas
226
What would blood investigation results show for VWD?
- Prolonged bleeding time
- APTT may be prolonged
- Factor VIII levels - moderately reduced
- Defective platelet aggregation with ristocetin (substance that aims to force platelet aggregation)
227
How is VWD managed?
- Transexaminc acid for mild bleeding
- Desmopressin (raised levels of vWF)
- Factor VIII concentrate
228
What is heparin induced thrombocytopenia?
- Development of an IgG antibody against a complex formed between platelets and heparin
- IgG/PF4/heparin complexes bind to and activate platelets = platelet consumption increased, thrombosis, skin necrosis
229
When are pts most at risk of heparin induced thrombocytopenia?
-After cardiac bypass surgery with large amounts of unfractioned heparin treatment
230
How does heparin induced thrombocytopenia present?
-Sharp fall in platelets 5-10 days after starting heparin
231
How is heparin induced thrombocytopenia managed?
- Life threatening: stop heparin immediately
| - Use alternative antioagulation even if platelets are low
232
What are the main haematological emergencies?
1. Neutropenic sepsis
2. Hyperviscosity syndrome
3. Tumour lysis syndrome
4. Acute sickle chest syndrome
233
What is tumour lysis syndrome?
- Chemo causes tumour lsis syndrome due to rapid death of cells when they are responding to treatment.
- IV rasburicase or IV allopurinol can be given pre-chemo to reduce risk
234
What are the diagnostic criteria for tuour lysis syndrome?
```
-Abnormality in >2 of the following:
>uric acid ^475 micromol
> K+ >6mmol or 25%^
>Phosphate >1.125 or 25%^
>Calcium >1.75 or 25%^
-Lab tumour lysis syndrome +:
>Increased serum creatining
>Cardiac arrhythmias or sudden death
>Seizure
```
235
What are hte complcications of tumour lysis syndrome?
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia
- Acute renal failure
236
How is tumour lysis syndrome treated?
- Aggressive IV fluid resuscitation
- Allopurinol or rasbicurase
- Electrolyte control
- Early dialysis referral
237
What is the definition of neutropenic sepsis?
- Neutrophil count of <0.5
- In a pt who is having anti-cancer treatment
- Temp >38 or other signs/symptoms consistent with clinical sepsis
238
What are the types of recgonised crises in sickle cell disease?
- Thrombotic, vaso-occlusive, painful crises
- Sequestration
- Acute chest syndrome
- Aplastic
- Haemolytic
239
What are the features of a thrombotic/painful crisis?
-Precipitated by: infection, dehydration, hypoxia
-Microvascular occlusion causing severe pain
-Infarcts occur in various organs:
>bones (avascular necrosis of the hip)
>Hand-foot syndrome
-Lungs
-Spleen
-Brain
240
What are the features of a sequestration crisis?
- Sickling within organs such as the spleen or liver
- Causes pooling of blood with worsening anaemia
- Mainly affects children as the spleen has not yet undergone atrophy
- Splenomegaly, hepatomegaly
- Severe anaemia and shock
- Required uregnt transfusion
241
What are the features of acute chest syndrome?
- Dyspnoea
- Chest pain
- Pulmonary infiltration
- Low p)2
242
What are the features of aplastic crisis?
- Occurs due to infection with parvovirus B19 (slapped cheek)
- Sudden reduction in marrow production (esp. RBCs)
- Sudden fall in Hb
- Usually self-limiting within 2/52
- May need transfusion
243
What are the features of haemolytic crisis?
- Rare
| - Fall in Hb due to ^ rate of haemolysis
244
How is acute sickle cell crisis managed?
- ABCDE
- Prompt, generous analgesia (IV opioids)
- Crossmatch blood, FBC, reticulocytes, cultures, CXR
- Rehydrate with IVI and keep warm
- 02
- Ceftriaxone if T>38
- Transfusion if Hb falls sharply
245
What is hypervisocisty synrome?
- An increase in whole blood viscosity due to raised immunoglobulins produced by malignant clones of plasma cells (myeloma)
- Sludging and lack of perfusion through microvasculature
246
What are the causes of hyperviscosity syndrome?
- Due to increased antibodies: myeloma, Waldenstrom's macroglobulinaemia
- Due to increased WBCs: CML, AML, ALL
- Due to increased RBCs: polycythaemia
247
What is the clinical presentation of hyperviscosity syndrome?
- Lethargy
- Headaches
- Confusion
- Cranial nerve defects
- Ataxia
- Retinal haemorrhages
- Dyspnoea and cough
- Mottling of the skin
248
How is hyperviscosity diagnsed?
- Clincical diagnosis
- Plasma viscosity level
- CT head to exclude other neuro causes of signs
- Globulin levels
- FBC and Ig levels
249
How is hyperviscosity managed?
- Plasmapharesis (if raised Ig levels)
- Leucophoresis (if raised WBCs)
- Avoid blood transfusions
- Start appropriate chemo
