Haematology Flashcards
1
Q
What percentage of blood do RBC make up?
A
45%
2
Q
Anaemia?
A
Decreased level of Hb or RBC in the blood below the reference for age and sex of the individual meaning that there is a decreased amount of O2 to tissue and organs
3
Q
In what circumstances would a patient present with decreased Hb but increased RCM?
A
3rd Trimester of pregnancy
4
Q
Average mcv?
A
800 - 90 fl
5
Q
Hb ranges for M and F?
A
M - 135 - 175 g/L
F - 115 - 160 g/L
6
Q
What are the physiological compensatory mechanisms for anaemia?
A
Increase HR
Increase oxygen dissociation
Increased red cell production
7
Q
What are the pathological consequences of anaemia?
A
myocardial and fatty liver changes
aggravate angina and claudication
skin and nail atrophic changes
CNS changes (cortex and basal ganglia)
8
Q
what is a key measure of anaemia?
A
Reticulocytes - baby RBC
9
Q
Microcytic anaemia in relation to MCV and Hb?
A
Decreased MCV and Decreased Hb
10
Q
Normocytic anaemia in relation to MCV and Hb?
A
Decreased Hb and normal MCV because the Hb produced are normal but there is a low number of them
11
Q
Macrocytic anaemia in relation to MCV and Hb?
A
Increased MCV and decreased Hb
12
Q
The greatest cause of microcytic anaemia?
A
Iron deficiency
13
Q
Aside from iron deficiency, give other causes of microcytic anaemia?
A
Chronic diseases such as renal failure and Thalassamia
14
Q
What can cause normocytic anaemia?
A
Acute blood loss
Chronic disease
Combined haematinic deficiency
15
Q
What is a combined haematinic deficiency?
A
Deficiency in iron, B12 and folate
micro and macro cancel each other out to try to look normal
- consider malabsorption
16
Q
Causes of Macrocytic anaemia?
FATRBCMD
A
Folate deficiency
Alcohol abuse
Thyroid - hypo
Reticulocytosis
B12 deficiency
Cirrhosis
Myelodysplasia
Drugs
17
Q
What investigations would be used to determine decreased B12?
A
Antibodies for intrinsic factor, coeliac, parietal cells
Schilling test - see how well a patient can absorb nuclear radioactive B12
Bone marrow biopsy + haematology referral
18
Q
Growth factors that stimulate blood cells production?
A
Erythropoietin
Thrombopoietin
G-CSF
Interleukin-5 (eosinophils)
19
Q
What is tumour necrosis factor?
A
They are pro-inflammatory cytokines released by activated macrophages and they can suppress erythropoiesis
20
Q
Dilutional anaemia?
A
21
Q
What are the clinical features of anaemia dependant on?
A
Severity and speed of anaemia
22
Q
Why may someone with anaemia be asymptomatic?
A
The gradual decrease in Hb allows for haemodynamic compensation and enhancement of CO2 carrying capacity - faster HR, Increased O2 dissociation and increased RC production
23
Q
Non-specific symptoms of anaemia?
A
fatigue
Faint
Breathless
Exacerbation of angina and claudication
Tachycardia
24
Q
What medication has been associated with macrocytic anaemia?
A
Azathioprine - immunosuppressant that suppresses the production of RBC in BM
25
what is a hyperchromatic blood film associated with?
The centre of the RBC is pale - \>1/3
Iron deficiency microcytic anaemia
26
What are the 2 forms of dietary iron?
Non-haem - diet - ferric to ferrous then dissolved and absorbed
Haem - Hb and myoglobin found in red and organ meat
27
What is the degradation product of ferritin?
Haemosiderin
28
Causes of iron loss?
Menstruation
GI bleed
Increased demand (growth and pregnancy)
Poor intake
Malabsorption
29
What is the difference that would be seen between iron deficiency and anaemia of chronic disease?
ID - Decreased serum iron and greater total iron-binding capacity
CD - Decreased serum iron and decreased total iron-binding capacity
30
Signs of microcytic anaemia?
Koilonychia
Atrophic Glostitis - bumpy tongue
Angular stomatitis - cold sores around the mouth
31
32
Investigations for microcytic anaemia?
Blood cultures + film - small and hyperchromatic
D serum ferritin
D serium iron but high total iron binding capacity (Transferrin saturation \<19%)
Increased transferrin receptor number
33
Management of iron deficiency microcytic anaemia?
Oral iron - ferrous sulphate to increase reticulocytes and Hb
Parenteral iron - IM or IV for those intolerant to oral iron or malabsorption
34
How does chronic disease ead to microcytic anaemia?
Decreased serum iron and decreased total iron binding capacity
Hepcidin is released in response to inflammation and it binds to export proteins (ferroportin) of partial cells and degrades them, iron is also trapped in macrophages and liver cells - so decreased iron in circulation
Hepcidin is produced by the liver
35
Difference between megaloblastic and non-megalobastic macrocyticanaemia?
Megaloblastic - Defective DNA synthesis of RBC causing them to have delayed nuclear maturation in relation to their cytoplasm - B12
Non-megaloblastic - No DNA impairment of RBC production but they are still large - cirrhosis, hypothyroidism
36
The absorption process of B12?
Liberated from protein complexes by gastric acid and pepsin to vit B12
Bound to intrinsic factor b=to be absorbed in the terminal ileum
stored in the liver
37
Causes of Decreased B12
Vegan
Pernicious anaemia (autoimmune against parietal cells)
Coeliac
Tapeworm
Achlorhydria - no gastric acid or HCL
Nitrous oxide - inactivates B12
38
Signs of macrocytic anaemia?
Glossitis
Angular stomatitis
Mild jaundice
Weakness, ataxia, paresthesia
Visual disturbances
39
Difference between B12 and folate deficiency?
Folate deficiency doesn't cause neuropathy
40
Investigations to confirm low folate?
Red cell folate and if not a dietary cause, look into small bowel disease
41
if a patient has megaloblastic anaemia, why do you not give them folic acid?
Folic acid could aggravate neuropathy caused by B12 deficiency
42
Investigations done to confirm macrocytic anaemia?
Blood cultures and film - hypersegmented + large
Decreased serum B12
Serum antibodies - parietal, coeliac and intrinsic factor
43
Management of B12 deficiency anaemia?
Hydroxocobalamin or oral B12
44
Drug that can cause folate deficiency?
Phenytoin - antiseizure
45
Causes of folate deficiency?
poor intake
malabsorption
Excessive usage (pregnancy, lactation, renal dialysis)
Drugs - phenytoin
46
What is aplastic anaemia?
Pancytopenia with hypercellularity - deficiency of all cell elements of blood with aplasia of bone marrow
Anaemia caused by bone marrow failure - you get a reduction in blood cell components and the ones made are faulty or trigger an immune reaction
47
Causes of aplastic anaemia?
pregnancy
newborn
alcohol excess
liver disease
hypothyroidism
Drugs - hydroxycarbamide (chemo therapy)
48
Clinical features of aplastic anaemia?
Bruising
Bleeding gums
epistaxis (nose bleeds) - acute haemorrhages of nostril, nasal cavity or nasopharynx
INCREASED RISK OF INFECTION DUE TO DECREASED NEUTROPPILS
49
Investigations of aplastic anaemia?
Blood count - pancytopenia + low reticulocytes
Bone marrow exam - hypercellular and increased fat space
Bone marrow trephine biopsy
50
Management of aplastic anaemia?
Stop causative agent
Blood and platelet transfusion
Bone marrow transplant
51
What is haemolytic anaemia?
Increased destruction of RBC and decreased circulating life span
52
What is the compensatory mechanism of haemolytic anaemia?
BM releases more reticulocytes
53
Intravascular causes of haemolytic anaemia?
Acquired - autoimmune or non-autoimmune
Inherited - membrane disorders, Hb abnormalities or metabolic disorders
54
examples of inherited membrane disorders than can cause haemolytic anaemia?
spherocytosis
Elliptocytosis
55
Examples of Hb abnormalities that can cause haemolytic anaemia?
Thalassaemia
Sickel cell
56
What metabolic defect can cause haemolytic anaemia?
Glucose-6-phosphate deficiency
57
What factors suggest haemolytic anaemia?
Increase plasma Hb and decreased RBC
Increased Hb binding to haptoglobin so decreased haptoglobin in total
+ve schumm test - Detect levels of methemalbumin which is haem and albumin
Haemosiderin
Haemoglobinuria
58
What are inherited haemolytic anaemias?
Anaemia caused by defects in components of mature blood cells e.g. membrane defects, Hb abnormalities or metabolic defects in the machinery of the RBC
59
Hereditary spherocytosis?
Decreased spectrin which is a structural protein of RBC - increased Na permeability
RBC is spherical, rigid and less deformable than a normal RBC
60
Clinical features of spherocytosis?
Asymptomatic
Jaundice, splenomegaly
Pigmented gall stones
61
Investigations of hereditary spherocytosis?
Increased reticulocytes + anaemia
Sphrocytes on blood film
Haemolysis - increased biliverdin
62
Management of hereditary spherocytosis?
Splenectomy after childhood
63
What is hereditary elliptocytosis?
RBC are elliptical in shape rather than standard biconcave
64
What is thalassaemia?
A group of disorders arising from 1 or multiple gene defects resulting in a reduced rate of production of 1 or more globin chains
Alpha and beta thalassaemia
65
Beta thalassaemia?
Little to no beta chain production so alpha bind with delta or gamma chains
66
What are the 3 forms of beta thalassaemia?
BT minor - trait - anaemia absent
BT intermedia - moderate anaemia - splenomegaly, leg ulcers, gall stones
BT major - severe anaemia in the first year of life, failure to thrive and recurrent infections
Hypertrophy of infective bone
**Thalassaemic facies** - large maxilla, parietal and frontal bone
Hepatosplenomegaly
67
Investigations used to diagnose thalassaemia?
Blood film - hyperchromatic microcytic
Increased reticulocytes
**Nucleated red cells in peripheral circulation**
**Hb electrophoresis - Increased Hbf and decreased HbA**
68
Management of beta thalassaemia?
Blood transfusion alongside iron-chelating agents (acerbic acid) to prevent iron overload
Long term folic acid
Bone marrow transplant
69
Alpha thalassaemia?
4x alpha genes per cell and sometimes some or all of them get deleted - manifestation of symptoms is dependant on how many genes have been deleted
70
Hb barts?
Complete absence of all alpha chains in a RBC
71
what is sickle cell anaemia?
family of Hb disorders where the sickle b-globin gene is inherited
Valine or lysine replaced by glutamic acid
In low O2 environments, Hb becomes insoluble and polymerised - rigid sickle shape = premature haemolysis and obstruction of the microcirculation
72
Exacerbating factors of sickle cell
infection, cold, hypoxia, dehydration and acidosis
73
How do the clinical features of sickle cell differ between child and adults?
The effects of vascular occlusion
Child - pain in hands and feet
Adult - pain in long bone, ribs, spine and **pelvis (**avascular necrosis of bone)
74
Other clinical features of sickle cell anaemia?
Enlarged spleen
Bone marrow aplasia
infection
75
Long term effects of sickle cell anaemia?
deformed bones
splenic atrophy
renal ischaemia
stroke
pigmented gall stones
ulcers
Acute chest syndrome
76
Investigations of sickle cell?
Heel prick and check if from high-risk area
Blood count - high reticulocytes with high Hb
Blood film - Sickled erythrocytes
Hb electrophoresis - HbSS
77
Management of sickle cell?
Avoid precipitating factors
Non-opiate adjuvant analgesics - P, NSAIDS
Blood transfusion
Hydroxycarbamide - increases HbF and is used in crisis
78
What is the sickle cell trait?
Normal blood count and film but symptoms come in extreme situation e.g. flying in a non-pressurised plane
79
Treatment of emergency sickle crisis?
analgesia - morphine and non-opioid adjuvant analgesia
Laxative
Anti-pruritic
Antiemetics - vomit
Anxiolytic - reduce anxiety
Antibiotic
80
How does glucose 6 dehydrogenase deficiency result in haemolytic anaemia?
G6PD - maintains levels of glutathione which protects the RBC against antioxidant injury and without it they get injured by antioxidants
81
Complications of G6PD?
Jaundice
Haemolytic anaemia
Acute haemolysis
82
Investigations to confirm G6PD deficiency?
G6PD in RBC
83
What to avoid if you have G6PD?
Flava beans
Drugs such as quinolones
84
Management of G6PD?
Remove causative agents and sometimes transfusion
85
Differences between the 2 types of autoimmune acquired haemolytic anaemia?
WARM AHA - IgG, autoimmune disorders 2º cause, management is high dose steroids, splenectomy or immunosuppressants
COLD - IgM, 2º cause is infection and management is to avoid cold exposure
86
What is autoimmune haemolytic anaemia?
Antigens on the surface of the patients RBC trigger an immunological response and get destroyed by autoimmune antibodies
Dependant on body temp
Antibodies attach to RBC causing extravascular haemolysis (spleen) or intravascular haemolysis (activation of complement)
87
What is the direct antiglobulin coombs test?
antibodies or complement attached to surface RBC - react with antiserum or monoclonal antibodies against the attached immunoglobulins or C3d
+ve - agglutination
88
Can drugs cause autoimmune haemolysis?
Yes
They can alter the structure of cell membrane resulting in intravascular haemolysis
They can alter the membrane of red blood cell making it antigenic - extravascular haemolysis
89
What are the 2 different types of non-autoimmune acquired haemolysis?
Paroxysmal nocturnal haemoglobinuria
Mechanical haemolytic anaemia
90
what is Paroxysmal nocturnal haemoglobinuria?
Dark urine at night and in the morning on waking
Deficiency in GPI anchor (CD59, CD55) which teethers proteins to the cell membrane of RBC so the RBC are more sensitive to haemolytic action of complement
intravascular haemolysis, venous thrombosis and bone marrow aplasia
91
Treatment of Paroxysmal nocturnal haemoglobinuria?
Blood transfusion
**Eculizumab** - binds to complement preventing haemolysis
Bone marrow transplant
92
What is mechanical haemolytic anaemia?
RBC injured through physical trauma in circulation e.g.
**Mechanical valves**
**prolonged marching** (RBC damaged in the feet)
Microangiopathic haemolysis - fragmentation of RBC in abnormal microcirculation causing malignant hypertension
93
What is a major complication of DVT?
Pulmonary embolism
94
Investigations of DVT?
Wells score \>2 - ask questions of factors that make you more prone to DVT
D-dimer - degradation product of fibrin - negative score is more helpful than a positive because positive can be caused by a range of different things
Thrombophilia
Underlying malignancy
Hommans test - tilt the leg
95
Describe virchow's triad and explain the pathophysiology of thrombus development?
Hypercoagulability
Stasis of blood flow
Endothelial injury
96
Risk factors for DVT?
Pregnancy - obstruction
Increased age
Hypertension
Surgery
Synthetic oestrogen
Obesity
Immobile
97
Signs of DVT?
warm and tender calf
Asymmetrical calf
Pitting oedema
98
Difference between signs/symptoms of arterial thrombosis and venous thrombosis?
**_Arterial_**
signs - decreased pulse, pale, cold finders and hands, dizziness
Symptoms - pins and needles, cold, numb, muscle pain in the affected area
**_Venous_**
Signs - swollen, red, warm to touch, tender
Symptoms - calf pain, tender
99
6 P's of limb iscahemia?
Pain
Pulseless
Paraesthesia
Paralysis
Pallor
Perishingly cold
100
MOA warfarin?
Inhibits Vit K reductase (oxidised to reduced) so gamma carboxyglutamic acid component of 10 9 7 2 isn't made so inhibiting the cascade
(glutamic acid, O2 and CO2)
101
Heparin MOA?
Binds to the enzyme inhibitor antithrombin 3 causing antithrombin to be activated
Inhibits thrombin and factor 10
102
What is used to monitor the effect of warfarin?
INR - international normalised ratio - a measure of how long it takes for a blood clot to form (measure extrinsic pathway)
APTT - Activated partial thromboplastin time - Measure of the intrinsic pathway
103
Oral anticoagulation that can be used for DVT?
Warfarin
Heparin
Fondaparinux, apixaban
104
What is the difference between lymphoblastic leukeaemia and myeloid leukaemia?
Lymphoblastic - malignancy of lymphoid tissue affecting B and T lymphocytes
Myeloid -proliferation of cells derived from the myeloblast e.g. eosinophil, basophil, neutrophil and monocytes
105
What is the commonest cancer in childhood?
Acute lymphoblastic leukaemia - malignancy of lymphoid tissue affecting B and T lymphocytes by arresting matruation =
uncontrolled proliferation of immature cells
Marrow failure
Tissue infiltration
106
Signs of tissue infiltration (Acute lymphoblastic leukaemia)?
Lymphadenopathy
Hepatospenomegaly
Orchidomegaly (testes)
107
What can be used to classify acute lymphoblastic leukaemia?
Morphological
Immunological
Cytogenic
108
Signs of marrow failure?
Anaemia
Infections
Bleeding
109
Investigations sued to diagnose acute lymphoblatic leukaemia?
BC + blood film (decreased WCC)
CXR + CT - lymphadenopathy
Lumber puncture - CNS involvement
110
Management of acute lymphoblatic leukaemia?
Blood transfusion
Fluids
PICC line (Hickmans line)
**Allopurinal** - to prevent tumour lysis syndrome
Chemo
Marrow transplant
**Thiopurine** - immunosupressant
111
What is haemtological remission?
No evidence of leukaemia in blood and normal/recovering blood count and \<5% blasts in a normal regenerting marrow
112
What is acute myeloid leukaemia?
Neoplastic proliferation of blast cells derived from marrow myeloid cells - immune cells eosinophils, neutrophils, basophills and monocytes
113
What are myelodysplatic syndromes?
Disorders that manifest as a result of marrow failure with life threatening risk of infection and bleeding
114
Complications of acute myeloid leukaemia?
Infection
Septicaemia
Fever
Increased plasma urate
Leukostasis - elevated blast cell count
115
Signs and symtpoms of acute yeloid leukaemia?
Marrow failure
Infiltration
116
Diagnosis of acute myeloid leukaemia?
Decreased WCC
Decreased blast cells peripherally
**Aur rods -** red staining needle like rods found in a bone marrow biopsy due to abnormal fusion of granules (cytoplasma of myeloblasts)
Peripheral blood film showing monoblasts
117
What is chronic myeloid leukaemia?
Uncontrolled cloncal proliferation of myeloid cells (they are all the same type of cell whereas acute is all the cells derived from the myeloblast)
118
What is present in \>80% of patients with chronic myeloid leukaemia?
Philadelphia chromosome
Mutation of chromosome 22 - affecting activity of tyrosine kinase
119
Symptoms of chronic myeloid leukaemia?
Decreased weight
Tired + fever + sweating
Abdo pain
Gout
120
Management of chronic myeloid leukaemia?
Imatinib - inhibits tyrosine kinase
Hydroxycarbamide
Allogeneic stem cell transplantation
121
Signs of chronic myeloid leukaemia?
Spleenomegaly
Hepatosplenomegaly
Anaemia
Bruising
122
Investigations to confirm chronic myeloid lukaemia?
Increased WBC
Decreased Hb
Increased Urate
Bone marrow hypercellular
Philadelphia gene - (cytogenetics)
Numerous granulocytic cells at different stages of differentiation
123
What is the hallmark of chronic lymphocytic leukaemia?
Progressive accumulation of a malignant clone of functionally incompetant B cells
124
Signs of chronic lymphocyti leukaemia?
Enlarged rubbery non-tender noders
Splenomealy
Hepatomegaly
125
Symptoms of chronic lymphocytic leukaemia?
usually found on routine bloods
Anaemia, prone to infection, sweats and anorexia
126
Complications of chronic lymphocytic leukaemia?
Autoimmune haemolysis
Infection
Marrow failure
127
Treatment of chronic lymphocytic leukameia?
Fludarabine + Rituximab + Cyclophosphamide - anticancer drugs
Steroids
Radiotheraphy
Stem cell transplant
Blood transfusion
128
What is the difference between leukamia and lymphoma?
Leukaemia - affects blood cells and bone marrow
Lymphoma - affects lymph nodes as solid tumour proliferations of lymphocytes accumulate in lymph nodes and cause lymphadenopathy
129
Hallmark of hodgkins lymphoma?
Reed-sternberg cells - abnormal lymphocytes that have more than 1 nucleaus
130
Lymph nodes affected in hodgkins lymphoma?
Cervial - supraclavicular - mediastinal
Through contagious spread from LN to LN
131
Risk factors for hodgkins lymphoma?
EBV
Benzene
Hisotry of infectious mononucleosis
An affected sibling
Post transplant
132
Symptoms of Hodgkins lymphoma?
Enalrged non-tender rubbery lymph nodes
Fever, weight loss, night swetas
**Alcohol indiced LN pain**
If large enough, the mass can obstructt the SVC
133
Signs of hodgkins lymphoma?
Localised and painless lymphadenopathy
Spleno or hepatomegaly
Cachexia - wasting of the body due to severe chronic illness
Anaemia
134
Investigations done to confirm hodkins lymphoma?
**Tissue diagnosis** - Core needle biopsy of lymph node
**Bloods** - FBC, Film, LFT,Hb, Urate - RS cells, LDH
**Imaging** - CXR, PET/CT
135
What is LDH?
Lactate dehydrogenase enxyme is used to convert sugars into energy for cells to use - increased needed for the proliferation of lymphocytes
136
How does EBV cause HL?
By activating **nuclear kappa light chain** which is a transcription factor - genes that promote proliferation
137
What is staging process is used to stage hodgkins lymphoma?
An Arbor staging
1 - confined to single lymph node
2 - 2 or more lymph nodes at the same side of the diaphragm
3 - involvement of both sides of the diaphragm
4- Extralymphatic tissue involement - liver and bone marrow
138
Differnce between type A and type B hodgkins lymphoma?
A - no symptoms other than itching
B - Unexplained fever, weight loss \>10% and drentching sweat and extranodal extention - breaking the confines of the capsule and affecting surrounding tissue
139
Management of hodgkins lymphoma?
1, 2, A - radiotherapy and short course chemo
3, 4, B - radiotherapy and long course Chemo
ABVD
140
ABVD?
Adriomycin
Bleomycin
Vinblastine
Dacarbazine
141
What is brentuximab?
Monoclonal antibody against CD30 used alongside chemo and stem cell transplant for relapse of hodgkins lymphoma
142
Sideeffects of radio and chemo therapy?
IHD, NHL, Hypothyroidism, Lund fibrosis
MYelosupression, alopecia, nausea , infertility, NHL
143
Index used to deteramin the prognosis of hidkins lymphoma?
Hasenclaver index
144
Non-hodgkins lymphomas?
Any tumours of lymph nodes without reed sterberg cells - mostly derived from B cells
145
Types of aggresive NHL?
Diffuse large B bell lymphoma
Burkitt's - CT 9/14 - MYC genes overexpressed - increased cell growth and metabolism
Mantle cell - CT 14/11 - BCL1 overexpression activating cyclin D! - cell growth
146
Difference of extranodal involvement of burkitt's lymphoma between african and non-african countries?
Africa - Jaw and EBV association
Non-african - Abdomen and no EBV association
147
Types of indolent NHL?
**Follicular** - overexpression of BCLR which normally prevents cell death
**Marginal zone** - Mucosa associated lymphoid tissue - lining of the stomach of those with chronic inflammation
**Lyphoplasmacytic** - BM, LN,Spleen - neoplastic cells produce immunoglobuin M proteins causing the blood to become thick (waldenstroms macroglobulinaemia)
148
What are the 2 different types of T cell lymphomas?
**Adult T cell lymphoma** - incorparates it's DNA into T cell DNA
**Mycosis fungoides** (cutaneous T cell lymphoma) - Sezary sydtome which is a genrealised red rash and blood film looks cerebriform - nucleaus looks like a brian
149
Signs and symptoms of NHL?
**Lymphadenopathy** (painless)
**Fever, sweating and weightloss**
**Extranodal involvement** -
GI - bowel obstruction
BM - fatigue, anaemia, bruising and infections
SC - spinal chord compression - loss of sensation in the legs
150
Diagnosis of NHL?
CT
LN core needle biopsy
151
Management of NHL?
Chemo and radio
Rituximab - kills CD20 +ve cells by antibody directed cytotoxicity and apoptosis
Rituximab, Cyclophosphamide, Hydroxydaunorubicin (adriomycin), Vincristine, Prednisolone
152
Myeloma?
Abnormal proliferation of plasma cells resulting in hypersecretiond of Ig and Ig fragments leading to the destruction of ograns
Mostly IgG - causes a decrease in other immunoglobulins
153
Diagnosis of Myeloma?
Urine contains **Bence jones** protein (Ig light chains of kappa or lambda types filtered throguh the kidneys)
154
Blood film appearance of myeloma?
IL6 and CD138
**Ms plasma cell**
Do you want to see my **perinuclear halo**?
I've **lots of RER** to show
I have **vacules with Ig** and my **cytoplasm is dark blue**
We can do **rouleaux** before my alarm goes off showing my **clockface chromatin**
Ms PC **occupies 10% of the room** and knows most men
155
Clinical features of myeloma?
**I-CRAB**
**I**nfections - marrow infiltration
**C**alcium elevation - increased osteoclast activity from signalling myeloma cells
**R**enal insufficency - bence jones proteins have a toxic and inflammatory effect on the kidneys
Normocytic nochromatic **A**naemia
**B**one lesions
156
Investigations done to confirm myeloma?
BLOODS - rouleaux, normocytic anaemia, increased calcium
BONE MARROW BIOPSY - \>10% cell infiltration
SERUM AND URINE ELECTROPHORESIS
XRAY - bone lesions e.g. pepper pots skull
157
Management of myeloma?
Analgesia
Biphosphonates - inhibit osteoclastic activity, verterbral fractures and pain
Surgery to fix vertebral collapse
local radiotherapy
Transfusions + erythropoisesis
Rehydration
Broad spec antibiotics or regular IV immunoglobulins
158
159
What is paraproteinaemia?
The presence of circulating immunoglobulins produced by a single clone of plasma cells
Monoclonal M bands on serum electrophoresis
160
Types of paraproteinaemias?
**Multiple myeloma**
**Waldenstroms macroglobulinaemia** - lymphoplasmacytic NHL which produces IgM paraproteins
**Primary amyloidosis**
**Monoclonal gammaopathy of uncertain significance** - not causes by a known condition
**Paraproteinaemia** in lymphoma or leukaemia
**Heavy chain disease**- neoplastic cells produce free Ig heavy chains - alpha chains can infilttrate the bowel wall causing malabsorption
161
Amyloidosis?
Extracellular deposits of amyloid proteins which are resistant to degredation leading to organ failure - T2DM, altzheimers
162
Differnce between primary and secondary amyloidosis?
Primary - proliferation of plasma cells with amyloidic genetic monoclonal immunoglobulins and has many systemic effects (macroglossia)
Secondary -derived from serum amyloid A (acute phas eproteins) reflecting chronic inflammation in rheumatioid arthiritis
163
Familial amyloidosis?
Mutations of transport proteins produced by the liver (transthyretin) c neuropathy
Found in serum and CNF and transports thyroxine and retinal binding protein bound to retinal
164
What are myeloproliferative disorders?
Disorders caused by clonal proliferation of haematopoietic myeloid stem cells in the bone marrow
165
List the blood cells and associated conditions?
RBC - polycythemia
WBC - Chronic myeloid leukaemia
Platelets - essential thrombocythemia
Fibroblasts - myelofibrosis
166
What is the difference between reactive and absolute polycythemia?
**Reactive** - Caused by decreased plasma volume making it look like the RBC mass has increased - dehydration, burns, stress, hypovolaemia
**Absolute** - (primary vera) increase in RBC mass due to spontaneous proliferation of 1 pluripotent stem cell in bone marrow - they proliferate without even needing EPO
(Secondary) due to hypoxia (high altitude, smoking) or inappropriate EPO secretion from a renal or hepatocellular carcinoma
167
Clinical features of polycythemia?
Can be asymptomatic and found on routine bloods
HYPERVISCOCITY - dizziness, headache, tinnitus and visual disturbance
Itching after a hot bath
Erythromelalgia - blocked perfusion to hands causing vascular peripheral pain and inflammation
Splenomegaly
Gout
arterial or venous thrombosis
168
Investigations used to diagnose polycythemia?
FBC
Hypercellular bone marrow
Increased RC mass
Erythropoietin levels
Splenomegaly
169
Management of polycythemia?
if they are \>60 + previous thrombus - hydroxycarbamide (increases fetal haemoglobin and decreases RBC count and platelets)
Alpha interferon - inhibits the growth of abnormal clones of stem cells
Aspirin
170
Essential thrombocythemia?
Clonal proliferation of megakaryocytes resulting in increased platelets resulting in microvascular occlusions and AV thrombosis
171
Symptoms of thrombocythemia?
Headache, atypical chest pain, light-headed, erythromelalgia
172
Management of essential thrombocythemia?
Aspirin
Hydroxycarbamide
173
Myelofibrosis?
Extensive scarring of bone marrow. So much scarring meaning that cells are not able to develop properly
Hyperplasia of megakaryocytes which produce platelet-derived growth factor leads to intense fibrosis of the bone marrow
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Blood film of a patient with myelofibrosis?
Tear drop RBC
Decreased Hb
Nucleated RBC
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Management of myelofibrosis?
Allogeneic stem cell transplant
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MOA Heparin?
Activates Antithrombin 3
Inhibits 10a and thrombin
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MOA tPa or streptokinase?
activate plasminogen to become plasmin
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MOA warfarin?
Vitamin K reductase inhibitor so the vitamin K dependant clotting factors (1972) don't have their gamma carboxyglutamic acid component and so they don't function
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3 main factors that stop bleeding?
Vasoconstriction
Platelet plug
Coagulation cascade
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Signs of vascular and platelet disorders?
Prolonged bleeding from cuts
Bleeding into the skin (bruising and purpura)
Bleeding from mucous membranes (epistaxis and bleeding gums)
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What are some vascular defects that can result in bleeding disorders?
poor vascular integrity means bleeding into tissue
Ehlers-danlos - low collagen
Scurvy - low vit C means low capillary integrity
Steroids
Osler-weber- rendu - abnormal blood vessel formation in skin, mucous membranes, the gut and even organs
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What is the difference between Haemophilia A and haemophilia B?
A - factor 8 deficiency and B is a factor 9 deficiency
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Signs of thrombophilia?
Arthropathy - bleeding in the joint
Haematoma - bleeding outside of blood vessels
increases PT time and decreased factor 8
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Why should people with haemophilia avoid IM injections and NSAIDS?
They slow down blood clotting time and increase the risk of gut bleeding - the decreased activity of platelets
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Management of Haemophilia A?
Minor - desmopressin - increases the release of clotting factor 8
Major - recombinant factor 8 to 50% the normal level
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Management of Haemophilia B?
Recombinant factor 9
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Acquired haemophilia?
unusual susceptibility to bleed mostly due to hypercoagulability
Slow or irregular blood clotting caused by a defect in the system of coagulation
Autoantibodies against factor 8
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Other causes of bleeding disorders?
Liver disease
Malabsorption
Anticoagulant medication
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