Clinical haematology Flashcards
Conditions and Presentations (229 cards)
1
Q
ALL
A
- Most common form of malignancy which affects children
- accounts for 80% of childhood leukaemia
- peak is around 2-5 years old
- boys affected more than girls are
2
Q
ALL bone marrow failure signs
A
anaemia: lethargy and pallor
neutropaenia: frequent or severe infections
thrombocytopenia: easy bruising, petechiae
3
Q
Other feautres of ALL
A
bone pain (secondary to bone marrow infiltration)
splenomegaly
hepatomegaly
fever is present in up to 50% of new cases (representing infection or constitutional symptom)
testicular swelling
4
Q
Types of ALL
A
common ALL (75%), CD10 present, pre-B phenotype
T-cell ALL (20%)
B-cell ALL (5%)
5
Q
Poor prognostic factors of ALL
A
age < 2 years or > 10 years
WBC > 20 * 109/l at diagnosis
T or B cell surface markers
non-Caucasian
male sex
6
Q
Myeloma- CRABBI
A
- calcium
- Renal
-Anaemia
-Bleeding
-Infetion
7
Q
Myeloma calcium
A
- hypercalcaemia
primary factor:
* increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
———————————————
much less common
* impaired renal function,
* increased renal tubular calcium reabsorption
* elevated PTH-rP levels
this leads to constipation, nausea, anorexia and confusion
8
Q
Myeloma - Renal
A
Presentation:
* dehydration
* increased thirst
monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
other causes of renal impairment in myeloma include
* amyloidosis
* nephrocalcinosis
* nephrolithiasis
9
Q
Anaemia- myeloma
A
bone marrow crowding suppresses erythropoiesis leading to anaemia
this causes fatigue and pallor
* normocytic normochromic anemia
10
Q
Bleeding myeloma
A
bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
11
Q
Bones myeloma
A
bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
this may present as pain (especially in the back) and increases the risk of pathological fractures
12
Q
Myeloma infection
A
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
13
Q
Other features of myeloma
A
amyloidosis e.g. macroglossia
carpal tunnel syndrome
neuropathy
hyperviscosity
14
Q
Myeloma bloods investigation
A
full blood count: anaemia
peripheral blood film: rouleaux formation
urea and electrolytes: renal failure
bone profile: hypercalcaemia
15
Q
Protein electophoresis investigation
A
raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
16
Q
Major diagnostic criteria for Myeloma
A
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
17
Q
Minor criteria of myeloma
A
- 10% to 30% plasma cells in a bone marrow sample.
- Minor elevations in the level of M protein in the blood or urine.
- Osteolytic lesions (as demonstrated on imaging studies).
- Low levels of antibodies (not produced by the cancer cells) in the blood.
18
Q
Bruising in children - neonates
A
Coagulation disorders
haemorrhagic disease of the newborn
haemophilia
Thrombocytopaenia
maternal alloimmune thrombocytopaenia
Also
birth trauma: cephalohaematoma
congenital infections e.g. rubella
19
Q
Infants bruising causes
A
Accidental injury
Non-accidental injury
Coagulation disorders
haemophilia
Thrombocytopaenia
ITP
Thrombocytopaenia with Absent Radius (TAR)
congenital infection
20
Q
Older children bruising causes
A
Accidental injury
Non-accidental injury
Coagulation disorders
haemophilia
von Willebrand’s disease
liver disease
Thrombocytopaenia
ITP
acute lymphoblastic leukaemia
meningococcal septicaemia
Thrombocytopaenia with Absent Radius (TAR)
congenital infection
21
Q
Common sites for bruises due to play
A
Shins
Elbows
Forehead
22
Q
Bruises of concern in children.
A
- excessive multiple bruises of different ages
bruise patterns which may indicate slapping, being gripped tightly (fingertip marks) or the use of inflicting instruments (e.g. belt)
sites which may raise concern include the face, ears, neck, buttocks, trunk or proximal parts of limbs
23
Q
Normal colour changes in bruises
A
initially red
then changes to purple, blue or black (over 1-3 days)
later fades to yellow or green
light bruises typically fade within 2 weeks, more severe bruising may take longer
24
Q
Haemophilia
A
X-linked recessive disorder of coagulation
- 30% of patients have no family history of the condition.
25
Hameophilia A
Deficiency of factor VIII
26
Christmas disease
Haemophilia B
Lack of factor IX
27
Features of haemophilia
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
28
Blood test findings in haemophilia
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
29
Haemophilia A and antibodies
10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.
30
Immune thrombocytopenia in children
ITP is am immune-mediated reduction in the platelet count
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. It is an example of a type II hypersensitivity reaction.
ITP more common acute in children than in adults, may follow an infection or vaccination
31
Features of ITP
bruising
petechial or purpuric rash
bleeding is less common and typically presents as epistaxis or gingival bleeding
32
Investigations of ITP
full blood count
should demonstrate an isolated thrombocytopenia
blood film
bone marrow examinations is only required if there are atypical features e.g.
lymph node enlargement/splenomegaly, high/low white cells
failure to resolve/respond to treatment
33
Managment of ITP
usually, no treatment is required
ITP resolves in around 80% of children with 6 months, with or without treatment
advice to avoid activities that may result in trauma (e.g. team sports)
other options may be indicated if the platelet count is very low (e.g. < 10 * 109/L) or there is significant bleeding. Options include:
oral/IV corticosteroid
IV immunoglobulins
platelet transfusions can be used in an emergency (e.g. active bleeding) but are only a temporary measure as they are soon destroyed by the circulating antibodies
34
Pernicious anaemia
- autoimmune disorder which affects the gastric mucosa, results in vitamin B12 deficiency.
- often delayed and subtle symptoms
- causes can include H.pylori, alcoholism, gastrectomy…
35
Pathophysiology of pernicious anaemia
antibodies to intrinsic factor +/- gastric parietal cells
intrinsic factor antibodies → bind to intrinsic factor blocking the vitamin B12 binding site
gastric parietal cell antibodies → reduced acid production and atrophic gastritis. Reduced intrinsic factor production → reduced vitamin B12 absorption
vitamin B12 is important in both the production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy
36
Risk factors of pernicious anaemia
more common in females (F:M = 1.6:1) and typically develops in middle to old age
associated with other autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison's, rheumatoid and vitiligo
more common if blood group A
37
Features of pernicious anaemia
anaemia features
lethargy
pallor
dyspnoea
neurological features
peripheral neuropathy: 'pins and needles', numbness. Typically symmetrical and affects the legs more than the arms
subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy
other features
mild jaundice: combined with pallor results in a 'lemon tinge'
glossitis → sore tongue
38
Invesigations for pernicious anaemia
full blood count
macrocytic anaemia: macrocytosis may be absent in around of 30% of patients
hypersegmented polymorphs on blood film
low WCC and platelets may also be seen
vitamin B12 and folate levels
a vitamin B12 level of >= 200 nh/L is generally considered to be normal
antibodies
anti intrinsic factor antibodies: sensivity is only 50% but highly specific for pernicious anaemia (95-100%)
anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically
Schilling test is no longer routinely done
radiolabelled B12 given on two occasions, firstly on its own, secondly with oral IF. Urine B12 levels are then measured
39
Managment of pernicious anaemia
vitamin B12 replacement
usually given intramuscularly
no neurological features: 3 injections per week for 2 weeks followed by 3 monthly treatment of vitamin B12 injections
more frequent doses are given for patients with neurological features
there is some evidence that oral vitamin B12 may be effective for providing maintenance levels of vitamin B12 but it is not yet common practice
folic acid supplementation may also be required
40
Complications of pernicious anaemia
Increased risk of gastric cancer
41
Lymphadenopathy
- enlarged lymph nodes.
42
Infective differential diagnosis for lymphadenopathy
infectious mononucleosis
HIV, including seroconversion illness
eczema with secondary infection
rubella
toxoplasmosis
CMV
tuberculosis
roseola infantum
43
Neoplastic causes of lymphadenopathy
leukaemia
lymphoma
44
Other causes of lymphadenopathy
autoimmune conditions: SLE, rheumatoid arthritis
graft versus host disease
sarcoidosis
drugs: phenytoin and to a lesser extent allopurinol, isoniazid
45
Massive haemorrhage definition
loss of one blood volume in a 24 hour period or the loss of 50% of the circulating blood volume in 3 hours.
A blood loss of 150ml/ minute is also included.
The normal adult blood volume is 7% of total adult body weight. The blood volume equates to between 8 and 9% of a child's body weight.
46
Complications of massive haemorrhage- hypothermia
Blood is refrigerated
Hypothermic blood impairs homeostasis
Shifts Bohr curve to the left
47
Hypocalcaemia complications in haemorrhage
Both FFP and platelets contain citrate anticoagulant, this may chelate calcium
48
Hyperkalaemia massive haemorrhage risk
Plasma of red cells stored for 4-5 weeks contains 5-10 mmol K+
49
Delayed type transfusion
Due to minor incompatibility issues especially if urgent or non cross matched blood used
50
Transfusion related lung injury
Acute onset non cardiogenic pulmonary oedema
Leading cause of transfusion related deaths
Greatest risk posed with plasma components
Occurs as a result of leucocyte antibodies in transfused plasma
Aggregation and degranulation of leucocytes in lung tissue accounts for lung injury
51
Coagulopathy
Anticipate once circulating blood volume transfused
1 blood volume usually drops platelet count to 100 or less
1 blood volume will both dilute and not replace clotting factors
Fibrinogen concentration halves per 0.75 blood volume transfused
52
Common causes of hepatomegaly
-Cirrhosis: if early disease, later liver decreases in size. Associated with a non-tender, firm liver
-Malignancy: metastatic spread or primary hepatoma. Associated with a hard, irregular. liver edge
-Right heart failure: firm, smooth, tender liver edge. May be pulsatile
53
Causes of hepatomegaly
viral hepatitis
glandular fever
malaria
abscess: pyogenic, amoebic
hydatid disease
haematological malignancies
haemochromatosis
primary biliary cirrhosis
sarcoidosis, amyloidosis
54
Causes of hepatosplenomegaly
chronic liver diseasewith portal hypertension
infections: glandular fever, malaria, hepatitis
lymphoproliferative disorders
myeloproliferative disorders e.g. CML
amyloidosis
55
Massive splenomegaly causes
myelofibrosis
chronic myeloid leukaemia
visceral leishmaniasis (kala-azar)
malaria
Gaucher's syndrome
56
Other causes of splenomegaly
portal hypertension e.g. secondary to cirrhosis
lymphoproliferative disease e.g. CLL, Hodgkin's
haemolytic anaemia
infection: hepatitis, glandular fever
infective endocarditis
sickle-cell*, thalassaemia
rheumatoid arthritis (Felty's syndrome)
57
Fissure in and
- Bright red rectal bleeding
- painful bleeding that occurs post defecation, small volumes
- associated with constipation
- Muco-epithelial defect usually in the midline posteriorly (anterior fissures more likely to be due to underlying disease)
58
Haemorrhoids
- bright red rectal bleeding
- post dedication bleeding on toilet paper and in pan
- altered bowel habit and history of straining
-no blood mixed with stool
- no local pain
- colon and rectum normal
- proctoscopy may show internal haemorrhoid, usually impalpable
59
Crohn’s disease
- Bright red or mixed blood
- bleeding may be accompanied by other symptoms such as altered bowel habit, malaise, history of tissues, assessed ‘
- Perineal inspection may show fissures or fistulae. Proctoscopy may demonstrate indurated mucosa and possibly strictures. Skip lesions may be noted at colonoscopy.
60
Ulcerative colitis
- bright red bleeding often mixed with stool
- Diarrhoea, weight loss, nocturnal incontinence passage of mucous PR
- Proctitis is most marked finding
Perianal disease is usually absent. Colonoscopy will show continuous mucosal lesion.
61
Rectal cancer
Bright red blood mixed volumes
- Alteration of bowel habit. Tenesmus may be present. Symptoms of metastatic disease.
Usually obvious mucosal abnormality. Lesion may be fixed or mobile depending upon disease extent. Surrounding mucosa often normal, although polyps may be present.
62
All patients rectal bleeding investigations
- DRE
- procto- sigmoidoscopy
- young patients need require bowel preparation with an enema and a flexible sigmoidscopy performed.
Patients with excessive pain and suspected of fissure can be given a GA or LAA
63
Fissure in ano managment
GTN ointment 0.2% or diltiazem cream applied topically is the usual first line treatment. Botulinum toxin for those who fail to respond. Internal sphincterotomy for those who fail with botox, can be considered at the botox stage in males.
64
Haemorrhoid managment
Lifestyle advice, for small internal haemorrhoids can consider injection sclerotherapy or rubber band ligation. For external haemorrhoids consider haemorrhoidectomy. Modern options include HALO procedure and stapled haemorrhoidectomy.
65
Inflammatory bowel disease managment
Medical management- although surgery may be needed for fistulating Crohns (setons).
66
Rectal cancer managment
Anterior resection or abdomino-perineal excision of the colon and rectum. Total mesorectal excision is now standard of care. Most resections below the peritoneal reflection will require defunctioning ileostomy. Most patients will require preoperative radiotherapy.
67
Disseminated intravasular coagulation
- process of coagulation and fibrinolysis are dysregulated, results in widespread clotting and resulting bleeding.
68
Causes of DIC
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
69
Diagnosis of DIC
platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
schistocytes due to microangiopathic haemolytic anaemia
70
Haemochromatosis features
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
'bronze' skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands
71
Reversible complications of haemochromatosis
Cardiomyopathy
Skin pigmentation
72
Irreversible complications of haemochromatosis
Liver cirrhosis**
Diabetes mellitus
Hypogonadotrophic hypogonadism
Arthropathy
73
Haemochromatosis
- autosomal recessive disorder of iron and absorption and metabolism results in iron accumulation
- mutation of the HFE gene on both copies of chromosome 6
74
Blood films
Manual examination of blood under microscope for abnormal shapes, sizes or inlclusions
75
Anisocytosis
Variation in size of red blood cell
- may be seen in myelodysplatic syndrome
76
Target
Red blood cells with central pigemented area surrounded by a pale area, surrounded by pale area.
Thicker cytoplasm on outside
Most commonly associated with iron deficiency anaemia and post-splenectomy
77
Heinz bodies
Individual blobs called inclusions
Blobs are denatures haemoglobin
Usually seen in G6PD deficiency and alpha thalassameia
78
Howell-jolly bodies
Howell-Jolly blobs of DNA material seen inside red blood cell
Spleen normally removes it
Commonly seen in patients with non-functioning spleens or severe anaemia
79
Reticulocytes
Immature red blood cells
Slightly larger than normal red blood cells (erythrocytes)
80
Schistocytes
fragments of red blood cells
81
Microangiopathic haemolytic anaemia (MAHA
small blood clots (thrombi) obstruct small blood vessels.
Result in hameolysis
82
Sideroblasts
immature red blood cells with a nucleus surrounded by iron blobs.
bone marrow cannot incorporate iron into the haemoglobin molecules.
Genetic defect or myelodysplastic syndrome
83
Smudge cells
Associated with chronic lymphocytic leukaemia
Ruptured white blood cells
84
Spherocytes
Sphere-shaped red blood cells that are bi-concave disc shaped
Associated with autoimmune haemolytic anaemia and hereditary spherocytosis
85
Three types of anaemia
Microcytic anaemia (low MCV)
Normocytic anaemia (normal MCV)
Macrocytic anaemia (large MCV)
86
Tails- microcytic anemia
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
87
Normacytic anaemia- AAAHH
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
88
Anaemia of chronic disease
- chronic disease
- chronic kidney disease due to reduced production of erythropoietin by the kidneys
Tx of erythropoietin
89
Megaloblastic anaemia
B12 deficiency
Folate deficiency
90
Noroblastic macrocytic anaemia
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
91
Symptoms of anaemia
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions, such as angina, heart failure or peripheral arterial disease
Pica
Hair loss
92
Signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
93
Koilonychia refers to spoon-shaped nails and can indicate iron deficiency anaemia
Angular cheilitis can indicate iron deficiency anaemia
Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency anaemia
Brittle hair and nails can indicate iron deficiency anaemia
Jaundice can indicate haemolytic anaemia
Bone deformities can indicate thalassaemia
Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease
94
Unexplained iron deficiency anaemia
Colonoscopy
OGD
Bone marrow biopsy `
95
Causes of iron deficient anaemia
Insufficient dietary iron (e.g., restrictive diets)
Reduced iron absorption (e.g., coeliac disease)
Increased iron requirements (e.g., pregnancy)
Loss of iron through bleeding (e.g., from a peptic ulcer or bowel cancer)
96
Bleeding in the GI tract
Cancer (e.g., stomach or bowel cancer)
Oesophagitis and gastritis
Peptic ulcers
Inflammatory bowel disease
Angiodysplasia (abnormal vessels in the wall)
97
How to test for iron deficiency anaemia
TIBC which directly relates to ferretin
98
ALL investigations
* Leucocytosis on FBC
* Blast cells on blood film and bone marrow
* Lymphoblasts are typically large with nucleoli, with very little cytoplasm and no granularity
* Immunophenotyping origin is a T or B cell, along with other immunological subtypes
* Periodic acid–Schiff (PAS) stains for carbohydrate material in ALL
99
When urgent FBC needed for leukaemia? (9)
## Footnote
If there are any of the following
* Pallor
* Persistent fatigue
* Unexplained fever
* Unexplained persistent or recurrent infection
* Generalized lymphadenopathy
* Unexplained bruising
* Unexplained bleeding
* Unexplained petechiae
* Hepatosplenomegaly
100
Managment of ALL
* combination chemotherapy
* CNS prophylactic agents are given to all patients with ALL
* Maintenace therapy for 2 years after
101
How to monitor if ALL therapy is effective?
* morphological remission is defined by blast count < 5%
* Assessment of minimal residual disease (MRD) – greater sensitivity than morphological assessment
PCR to amplify the characteristic clonal rearrangements of:
* Immunoglobulin genes in B-cell ALL
* T-cell receptor genes in T-cell ALL
With the detection of 1 leukaemic cell in 10,000 cells in the bone marrow
102
Complications of ALL
* Increased risk of infection (use prophylactic antibiotics)
* CNS involvment
* Chemotherapy toxicity- mucositis, neutropenic fever, and cardiotoxicity.
103
Side effects of Methotrexate
* Mucositis
* Myelosuppression
* Pulmonary fibrosis
* Liver fibrosis
104
cautions of Methotrexate
* photosensitivity
* dehydration (increased risk of toxicity)
* diarrhoea
* peptic ulcer disease.
105
Contradicting medications methotrexate
*** trimethoprim** or **co-trimoxazole**- bone marrow aplasia
* **chemotherapeutic agents** and **mono-clonal antibodies **increase risk of myelosuppression
106
Monitoring required with Methotrexate?
* Full blood count
* renal function
* liver function tests
## Footnote
done before starting treatment and repeated weekly until the patient is established on the drug. After this, they should be monitored every 2-3 months.
107
causes of microcytic anaemia
* Iron deficicinecy anaemia
* Sideroblastic anemia
* lead poisoning
* Thalassemia
* Iron loading anaemia
108
Side effects of iron tablets
diarrhoea, constipation, black stools, abdominal pain, nausea
109
Oral Iron and Levothyroxine
* advise patients to take at least 4 hours apart.
* iron reduces uptake of levo
110
Signs and symptoms of microcytic anaemia
* Fatigue and Weakness
* Pallor
* Shortness of Breath
* Palpitations
* Cold intolerance
* Iron-deficiency anaemia specific:
* Nail changes such as koilonychia (spoon-shaped nails)
* Atrophic glossitis
* Angular stomatitis
* Pica
111
Classification of VWD
* Type 1 VWD: Partial quantitative deficiency in VWF
* Type 2 VWD: Qualitative defects in VWF (e.g. decreased adhesion to platelets or factor VIII)
* Type 3 VWD: Almost complete deficiency of VWF
112
signs of VWD
* Excess or prolonged bleeding from minor wounds
* Excess or prolonged bleeding post-operatively
* Easy bruising
* Menorrhagia
* Epistaxis
* GI bleeding
113
Investigation for VWD
* Normal PT and TT
* **prolonged APTT** (functional factor VIII deficiency) and bleeding time.
* Von Willebrand factor level and activity assay
114
Acute bleeding VWD managment
* Desmopressin
* Tranexamic acid can be given for minor bleeding or prior to surgery on its own or as an adjunctive therapy to desmopressin or concentrates
* VWF-FVIII concentrates should be used if the above are unsuccessful and bleeding is persistent
115
VWD which factor affected?
clotting factor VIII
116
Acute emergency myeloma
* Acute renal failure – swift treatment of volume depletion, early involvement of renal physicians
* Hypercalcaemia – fluid and bisphosphonates needed
* Hyperviscosity – plasmapheresis
* Spinal cord compression – s radiotherapy emergency
117
Haematopoietic stem cell transplantation
* consider this option up to the age of 70 years
* induction therapy
* conditioning regimen (high-dose melphalan) followed by autologous stem cell transplan
118
What is induction therapy
* **nonchemotherapeutic** (eg. bortezomib, thalidomide and dexamethasone) (VTD) given together with **Daratumumab** (monoclonal antibody binding CD38) (DVTD).
* **VTD with DVTD **
119
Patients unsuitable for stem cell transplantation myeloma
* melphalan, prednisolone and thalidomide (MPT)
* patients likely to relapse after
* supportive managment
120
Complications of myeloma
* Bone Disease
* renal dysfunction
* infection
* anaemia
121
factors 1 to 4
* Factor I is fibrinogen.
* Factor II is prothrombin.
* Factor III is tissue factor (TF in the image above).
* Factor IV is calcium. EDTA in purple blood tubes binds to calcium to prevent blood from clotting before it has been analysed.
122
tumour lysis syndrome investigations
* U&E: Potassium and phosphate are usually raised, raised Cr suggestive of AKI/renal failure.
* Calcium: Typically low in tumour lysis syndrome.
* Uric acid: Usually elevated.
* ECG: To identify any metabolic abnormalities such as hyperkalaemia that may precipitate life-threatening arrhythmias.
123
Managment of tumor lysis syndrome
```
```* **Correction of electrolyte imbalances**: This may require dialysis in severe cases.
* **Administration of intravenous fluids**: To help flush out the intracellular contents released by the dying tumour cells.
* Medications: **Rasburicase**
124
Rasburicase mechanism
transforms uric acid into allantoin. Allantoin is more soluble in urine than uric acid, and more easily eliminated by the kidney.
125
Signs and symptoms of tumour lysis syndrome
* Dysuria or oliguria
* Abdominal pain
* Weakness
* Nausea or vomiting
* Muscle cramps
* Seizures
* Cardiac arrhythmias
* Gout/joint swelling
126
127
Tumour lysis syndrome findings
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
128
Cairo-Bishop scoring system
abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.
* uric acid > 475umol/l or 25% increase
* potassium > 6 mmol/l or 25% increase
* phosphate > 1.125mmol/l or 25% increase
* calcium < 1.75mmol/l or 25% decrease
129
Electrolyte changes seen with transfusion
* hypocalemia
* hyperkalaemia
130
AML
* Malignancy
* uncontrolled proliferation of myeloid precursors in the bone marrow
* leading to bone marrow failure and the accumulation of **immature white blood cells (blasts) in the peripheral blood.**
131
Epidemiology of AML
* Primarily affects adults
* Idiopathic
* exposure to ionizing radiation
132
Signs and symptoms of AML
* Bone marrow failure – anaemia, bleeding, infections
* Signs of tissue infiltration, including hepatomegaly, splenomegaly and gum hypertrophy
* Central nervous system involvement is rare
* Constitutional symptoms such as fever and unintentional weight loss
133
Investigations of AML
* blood tests (leucocytosis)
* blood film- blasts
* Blood marrow biopsy
* hypercellular marrow
* the presence of blasts (usually >50%)
* Sometimes Auer rods
134
NICE urgent FBC within 48hrs
* Pallor
* Persistent fatigue
* Unexplained fever
* Unexplained persistent or recurrent infection
* Generalized lymphadenopathy
* Unexplained bruising
* Unexplained bleeding
* Unexplained petechiae
* Hepatosplenomegaly
135
Managment of AML
* chemotherapy (lasts 5-10 days)
* Bone marrow transplant
* Prophylactic antimicrobials
* Blood products and growth hormone therapy
* offer all crypopreservation
136
AML prognosis
* 3-year survival rate 20%
* 30% cure rate with chemotherapy
137
How is AML classified morphologically according to the French–American–British (FAB) classification?
AML is classified into eight subtypes (M0–M7).
138
What does the FAB classification system for AML include?
The FAB classification system includes subtypes M0 to M7 based on morphological appearance.
139
What is the role of Sudan Black in cytochemistry for AML?
Sudan Black stains lipid material in myoblasts.
140
Which cytochemical stain is used to identify monocytic variants in AML?
Nonspecific esterase is used, which stains monocytic variants in AML (M5)
141
What are common tissue infiltration sites for AML?
* skin
* liver
* gums.
142
How does the release of lysozyme from malignant cells affect AML patients?
* damange to the renal tubules
* potassium leak and hypokalemia.
143
significance of the translocation t(15;17) in AML?
confirms acute promyelocytic leukemia (APML; M3 subtype) and confers a good prognosis.
144
What cytogenetic abnormality is associated with a better prognosis in the M2 subtype of AML?
translocation t(8;21).
145
How does t(15;17) affect the morphological appearance of promyelocytes in APML?
Hypergranular promyelocytes are seen, except in the M3 variant, which is hypogranular.
146
What is the utility of immunophenotyping in leukemia?
cell markers to distinguish AML from ALL if there are difficulties.
147
What can be observed on a blood film showing AML?
blast cells
148
Amyloidosis
* abnormal protein, called amyloid, builds up in organs and tissues, impairing their function.
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Types of amyloidosis (4)
* AL (primary)
* AA (secondary)
* hereditary
* familial amyloidosis
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AL amyloidosis proteins
light chains of immunoglobulins produced by plasma cells.
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conditions are commonly associated with AA amyloidosis? (3)
chronic inflammatory conditions such as
* rheumatoid arthritis
* inflammatory bowel disease
* chronic infections.
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What protein accumulation characterizes hereditary amyloidosis?
accumulation of mutant transthyretin (TTR) protein.
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common symptoms of amyloidosis?
* Fatigue
* weight loss
* swelling of the ankles and legs
* shortness of breath
* irregular heartbeats.
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How is amyloidosis diagnosed?
* Biopsy of affected tissue
* staining with Congo red dye
* apple-green birefringence under polarized light.
* further analysis with immunohistochemistry or mass spectrometry.
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Organs affected by amyloidosis
* kidneys
* heart
* liver
* nervous system
* gastrointestinal tract.
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Vaccinations post Spelenctomy
* Pneumococcal vaccination (with regular boosters every 5 years).
* Seasonal influenza vaccination (yearly, typically every autumn).
* Haemophilus influenza type B vaccination (one-off).
* Meningitis C vaccination (one-off).
Low does phenoxymethylpenicillin or clarithromyocin or erythromycin for life
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Indications for splenectomy
* trauma and rupture
* hypersplenism
* haemolytic anemia
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Non-Hodgkin's lymphoma
* Lymphoid malignancy
* absence of Reed-sternberg cells
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Epidemiology of NHL
* More common in males
* affects all ages equally
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Infectious associations with NHL (8)
* Helicobacter pylori – gastric MALT (mucosa-associated lymphoma tissue) lymphoma
* Epstein–Barr virus – Burkitt lymphoma (high-grade NHL) and AIDS-related CNS lymphoma
* hepatitis C virus – diffuse large B-cell lymphoma and splenic marginal zone lymphoma
* human T-cell lymphotropic virus type 1 (HTLV1) – T-cell lymphoma
* HIV/AIDS
* post-organ transplant
* Autoimmunse disorder
* inherited disorders affecting DNA repair
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Classification of NHL
* 30 different types
* cell of origin – B cell or T cell;
* pathological grade – high grade (aggressive) or low grade (indolent)
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diffuse large B-cell lymphoma (DLBCL)
* 60-70% cure rate and approaching 90% in young, fit patients
*
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Prognosis of NHL
5-year survival for treated patients with:
Low-grade lymphoma is typically around 30%
High-grade disease is 50%
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NHL investigation
* LDH blood test
* Normocytic anaemia or haemolytic anaemia
* Paraprotein
* blood films
* biospy
* Cytogenetics (t(11;14)
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Low-grade, indolent NHL managment
* **asymptomatic patients** 'watch and wait' until there is evidence of symptoms/organ failure
* ** stage I disease**, local radiotherapy to nodal sites can be used
* **advanced systemic disease,** immunochemotherapy is usually given – 'rituximab in combination with chemotherapy or obinutuzumab with chemotherapy is now the preferred therapy for most indolent NHLs.
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Sickle cell anaemia
* autosomal recessive
* normal haemoglobin (where variable HbS is present) tends to form abnormal haemoglobin molecules
* (HbS) upon deoxygenation leading to distortion of RBCs.
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Epidemiology of sickle cell disease
Central and West African descent
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Vaso-occlusive crises
* Primarily caused by microvascular obstruction due to RBC sickling and inflammation
* May be triggered by local hypoxia (eg. in cold weather)
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Vaso-occlusive crisis symptoms
severe pain
swelling
fever.
It can affect various parts of the body, such as the bones, joints, and abdomen.
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Managment of Vaso-occlusive crises
* analgesics
* hydration
* oxygen therapy
* treatment of any underlying infections or triggers.
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complications of SCD
* Splenic infarction and subsequent immunocompromise
* Sequestration crisis
* Osteomyelitis
* Stroke
* Dactylitis
* Poor growth
* Chronic renal disease
* Gallstones
* Retinal disorders
* Priapism
* Pulmonary fibrosis and pulmonary hypertension
* Iron overload from repeated blood transfusions
* Red cell aplasia (due to parvovirus B19 infection in the presence of chronic haemolytic anaemia)
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SCD managment
* peak flow
* FBC
* Reticulocytosis and unconjugated hyperbilirubinemia may be noted
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SCD blood film finding
* characteristic sickle cells
* target cells
* reticulocytosis with polychromasia
* features of functional hyposplenism (Howell–Jolly bodies, nucleated red cells)
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SCD frequent crises managment
Hydroxycarbamide
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SCD newer treatment
* **crizaniluzumab** (p-selectin inhibitor) for treatment of pain crises
* **voxelotor** (haemoglobin oxygen-affinity modulator) for haemolytic complications
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What is the final product of hemostasis?
Stable fibrin clot
## Footnote
The stable fibrin clot is formed from the conversion of fibrinogen to fibrin by thrombin.
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What does the fibrinolytic system do?
Breaks down fibrinogen and fibrin
## Footnote
The activation generates plasmin, which is responsible for the lysis of fibrin clots.
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What is a critical enzyme necessary for both coagulation and fibrinolysis?
Plasmin
## Footnote
Plasmin is the central proteolytic enzyme involved in the breakdown of fibrin.
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What happens to coagulation and fibrinolysis in DIC?
They are dysregulated
## Footnote
DIC results in widespread clotting and resultant bleeding.
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What is a critical mediator in DIC?
Tissue factor (TF)
## Footnote
TF is released after vascular damage and plays a major role in the development of DIC.
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Which cytokines are involved in the release of tissue factor?
Interleukin 1, tumor necrosis factor, endotoxin
## Footnote
These cytokines trigger the release of TF, particularly in septic conditions.
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List some causes of DIC.
* Sepsis
* Trauma
* Obstetric complications
* Malignancy
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What are the typical blood picture findings in DIC?
↓ platelets, ↓ fibrinogen, ↑ PT & APTT, ↑ fibrinogen degradation products
## Footnote
Schistocytes may also be present due to microangiopathic hemolytic anemia.
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What is Haemophilia A caused by?
Deficiency of factor VIII
## Footnote
Haemophilia B, also known as Christmas disease, is due to a lack of factor IX.
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What are the common clinical features of haemophilia?
* Haemoarthroses
* Haematomas
* Prolonged bleeding after surgery or trauma
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What is the typical blood test result for a patient with haemophilia?
Prolonged APTT; bleeding time, thrombin time, prothrombin time normal
## Footnote
These results are indicative of coagulation factor deficiencies.
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Alpha-thalassaemia is due to a deficiency of _______.
Alpha chains in haemoglobin
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How many alpha-globulin genes are located on chromosome 16?
2 separate alpha-globulin genes
## Footnote
The number of affected alleles determines the clinical severity.
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What is Hb H disease?
Caused by 3 affected alpha globulin alleles
## Footnote
Results in a hypochromic microcytic anemia with splenomegaly.
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What happens when all 4 alpha globulin alleles are affected?
Death in utero (hydrops fetalis)
## Footnote
This condition is also known as Bart's hydrops.
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What is beta-thalassaemia caused by?
Absence of beta globulin chains
## Footnote
It is located on chromosome 11.
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What are some features of beta-thalassaemia?
* Failure to thrive
* Hepatosplenomegaly
* Microcytic anaemia
* HbA2 & HbF raised, HbA absent
193
What is a common management strategy for beta-thalassaemia?
Repeated transfusions
## Footnote
This leads to iron overload, necessitating iron chelation therapy.
194
Sickle-cell anaemia results from the synthesis of which abnormal haemoglobin chain?
HbS
## Footnote
It is more common in people of African descent.
195
What substitution occurs in the beta chains in sickle-cell disease?
Glutamate is substituted by valine
## Footnote
This substitution decreases the water solubility of deoxy-Hb.
196
What is the definitive diagnosis of sickle cell disease?
Haemoglobin electrophoresis
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What is essential thrombocytosis?
A myeloproliferative disorder with megakaryocyte proliferation
## Footnote
It results in overproduction of platelets.
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What is the typical platelet count in essential thrombocytosis?
> 600 * 10^9/l
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What are some features of polycythaemia vera?
* Pruritus
* Splenomegaly
* Hypertension
* Hyperviscosity
* Thrombosis
200
What mutation is present in approximately 95% of patients with polycythaemia vera?
JAK2 mutation
201
What is the first-line treatment for polycythaemia vera?
Venesection
## Footnote
This is used to keep the haemoglobin in the normal range.
202
What are the diagnostic criteria for JAK2-positive polycythaemia vera?
A1: High haematocrit or raised red cell mass; A2: Mutation in JAK2
203
What does a low ESR indicate in polycythaemia vera?
It may be an additional feature
## Footnote
Typically observed alongside other symptoms.
204
What is a significant cause of morbidity and mortality in polycythaemia vera?
Thrombotic events
205
True or False: Polycythaemia vera can progress to acute leukaemia.
True
206
What is Warfarin?
An oral anticoagulant used for managing venous thromboembolism and reducing stroke risk in atrial fibrillation patients
## Footnote
Warfarin has been largely replaced by direct oral anticoagulants (DOACs) which require less monitoring.
207
What is the mechanism of action of Warfarin?
Inhibits epoxide reductase, preventing the reduction of vitamin K to its active hydroquinone form
## Footnote
This affects the carboxylation of clotting factors II, VII, IX, and X, and protein C.
208
What mnemonic is used to remember the clotting factors affected by Warfarin?
1972
## Footnote
This refers to factors II, VII, IX, and X.
209
What are the indications for using Warfarin?
Mechanical heart valves, venous thromboembolism, atrial fibrillation
## Footnote
Target INR varies based on condition.
210
What is the target INR for patients with mechanical heart valves?
Depends on valve type and location
## Footnote
Mitral valves generally require a higher INR than aortic valves.
211
What is the target INR for venous thromboembolism when using Warfarin?
2.5; if recurrent, 3.5
## Footnote
For atrial fibrillation, the target INR is also 2.5.
212
How are patients monitored while on Warfarin?
Using the INR (international normalized ratio)
## Footnote
This is the ratio of the patient's prothrombin time over the normal prothrombin time.
213
What is a consideration regarding the half-life of Warfarin?
Warfarin has a long half-life and achieving a stable INR may take several days
## Footnote
Loading regimes and computer software are often used to adjust the dose.
214
What factors may potentiate the effects of Warfarin?
* Liver disease
* P450 enzyme inhibitors (e.g., amiodarone, ciprofloxacin)
* Cranberry juice
* Drugs displacing Warfarin from plasma albumin (e.g., NSAIDs)
* Inhibiting platelet function (e.g., NSAIDs)
## Footnote
These factors can increase the risk of bleeding.
215
What are common side effects of Warfarin?
* Haemorrhage
* Teratogenic effects
* Skin necrosis
* Purple toes
## Footnote
Skin necrosis occurs due to a temporary procoagulant state when starting Warfarin, often managed with concurrent heparin administration.
216
True or False: Warfarin can be used in breastfeeding mothers.
True
## Footnote
Warfarin is teratogenic but can be considered safe during breastfeeding.
217
Fill in the blank: Warfarin works by inhibiting _______.
epoxide reductase
## Footnote
This inhibition prevents the reduction of vitamin K.
218
What is the risk associated with initiating Warfarin therapy?
Temporary procoagulant state leading to thrombosis and skin necrosis
## Footnote
This can occur due to reduced biosynthesis of protein C.
219
What are target cells associated with?
Sickle-cell/thalassaemia, Iron-deficiency anaemia, Hyposplenism, Liver disease
## Footnote
Target cells are red blood cells that have a bullseye appearance due to abnormal hemoglobin distribution.
220
What condition is indicated by 'tear-drop' poikilocytes?
Myelofibrosis
## Footnote
Tear-drop poikilocytes are red blood cells that are shaped like teardrops, often seen in myelofibrosis.
221
Spherocytes are associated with which conditions?
Hereditary spherocytosis, Autoimmune hemolytic anaemia
## Footnote
Spherocytes are spherical red blood cells that can be seen in various hemolytic anemias.
222
Basophilic stippling can be a sign of which conditions?
Lead poisoning, Thalassaemia, Sideroblastic anaemia, Myelodysplasia
## Footnote
Basophilic stippling is characterized by the presence of small blue granules in red blood cells, indicating certain types of anemia.
223
What do Howell-Jolly bodies indicate?
Hyposplenism
## Footnote
Howell-Jolly bodies are remnants of DNA in red blood cells, often seen when the spleen is not functioning properly.
224
Heinz bodies are associated with which conditions?
G6PD deficiency, Alpha-thalassaemia
## Footnote
Heinz bodies are aggregates of denatured hemoglobin and are indicative of oxidative stress in red blood cells.
225
What conditions are indicated by schistocytes ('helmet cells')?
Intravascular haemolysis, Mechanical heart valve, Disseminated intravascular coagulation
## Footnote
Schistocytes are fragmented red blood cells often associated with severe hemolytic processes.
226
What do 'pencil' poikilocytes indicate?
Iron deficiency anaemia
## Footnote
Pencil poikilocytes are elongated red blood cells that suggest iron deficiency.
227
Burr cells (echinocytes) are associated with which conditions?
Uraemia, Pyruvate kinase deficiency
## Footnote
Burr cells have a spiky appearance and indicate various metabolic disturbances.
228
Acanthocytes are associated with which condition?
Abetalipoproteinemia
## Footnote
Acanthocytes have irregular projections and are linked to lipid metabolism disorders.
229
What does the presence of hypersegmented neutrophils indicate?
Megaloblastic anaemia
## Footnote
Hypersegmented neutrophils are indicative of vitamin B12 or folate deficiency.
