Haematology Flashcards
1
Q
What is the mechanism of action of warfarin?
A
Inhibition of vitamin K epoxide reductase
2
Q
Where in the body is vitamin B12 absorbed?
What factor is needed for this process?
What is the deficiency of this vitamin called?
A
Terminal ileum. Intrinsic factor binds to dietary vitamin B12 and allows for its absorption in the terminal ILEUM. Absence of intrinsic factor (can be due to destruction by an antibody), leads to vitamin B12 deficiency.
Pernicious anaemia
3
Q
What is pernicious anaemia?
Some other causes of this deficiency?
A
In pernicious anemia, there’s increased production of overzealous IgA antibodies against intrinsic factor or the parietal cells.
This interferes with intrinsic factor’s ability to bind to B12. Resulting in vitamin B12 deficiency.
B12 deficiency can be due to
- Decreased dietary intake
- Impaired absorption
- Crohn’s disease: enterocytes in the terminal ileum are often damaged, so B12 can’t bind to transcobalamin to get to the target tissues.
- Gastric bypass: the ingested food passes through the stomach quickly, so even if intrinsic factor is produced, it can’t get to the food to bind B12.
4
Q
What are the symptoms of Vitamin B12 deficiency?
What would you see on a blood film?
A
Symptoms
- Glossitis (swollen tongue)
- Neurological symptoms
Blood film - Hypersegmented neutrophils (5+ lobes)
5
Q
What types of anaemia does
- iron deficiency
- folate deficiency
- B12 deficiency
cause?
A
6
Q
Name 5 Signs and symptoms of anaemia?
A
7
Q
What are some causes of anaemia in the elderly? Why are they more at risk?
A
8
Q
What are the components needed to make functional red blood cells?
A
9
Q
What are some examples of anaemias that occur because of a problem with
- Iron
- Amino acids/globins
- Blasts?
A
.
10
Q
What is the role of
- Ferric reductase?
- Ferritin?
- Ferroportin?
- Transferrin?
A
Ferric reductase - reduced Fe3+ to Fe2+
Ferritin - how iron is stored, mainly in the liver. (20-30% of our iron iOS stored as ferritin, 65% as haemoglobin, the rest as haemosiderin, myoglobin etc)
Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. Ferroportin is the only known iron exporter.[2]
After dietary iron is absorbed into the cells of the small intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream.
Transferrin - transports Fe3+
11
Q
What is haemosiderin?
A
Breakdown product of ferritin.
12
Q
What are the causes of iron deficiency? Give examples for each category.
A
Inadequate diet - eg. vegan, elderly reduced appetite
Increased requirement - eg pregnancy, growth in children
Decreased absorption - eg. Crohn’s, bowel resection
Blood loss - eg. menstruation, gastro, urinary, lung
13
Q
What causes increased absorption of iron? name 5.
A
Iron 2+
Vitamin C
14
Q
What causes decreased absorption of iron? name 5.
A
15
Q
What is the role of hepcidin?
Where is it made?
What does it bind to, and what result does this have?
What anaemia is this process related to?
Hepcidin is low when?
A
Master regulator of iron absorption.
Made in the liver.
Binds to ferroportin so iron can’t be absorbed
Anaemia of chronic disease, haemolysis.
16
Q
What GI investigations would you do for anaemia?
A
FIT = faecal immunochemical test
tTG tests for coeliac disease
17
Q
What are some causes of macrocytic megaloblastic anaemia?
A
18
Q
What are some causes of macrocytic non-megaloblastic anaemia?
A
Pregnancy
Alcohol
Liver disease
Hypothyroidism
19
Q
What investigations for B12 and folate deficiency?
A
20
Q
Describe the stages of erythropoeisis
Where does it take place
Lifespan of a RBC?
A
RBC’s develop in the BONE MARROW from a common progenitor cell.
120 days
21
Q
What are the components of haemoglobin?
What globin chains make up HbA, HbF and HbA2?
A
Haem, iron, globin.
HbA (adult) = 2 alpha, 2 beta
HbF (foetal) = 2 alpha, 2 gamma
HbA2 = 2 alpha, 2 delta
22
Q
Production - what growth factors are involved in erythropoeisis and where are they made?
Removal of defective cells - where?
A
Growth factors - erythropoietin made by kidney. Plus GM-CSF. (granulocyte-macrophage colony stimulating factor).
Production also needs iron, Vit B12, folate, amino acids.
Defective cells are removed by macrophages in the spleen and liver. Macrphages in bone marrow prevent damaged RBS’s from entering circulation.
23
Q
What enzymes are needed for metabolism of RBCs?
A
G6PD - protects RBCs from oxidative stress
Pyruvate kinase - for ATP production
24
Q
Anaemia - definition?
Levels? Men, women.
What is haematocrit?
Why would haematocrit be low?
A
Reduced haemoglobin concentration below the lower limit of the reference range for age and sex.
< 130 g/L in men
< 120 g/L in women
Haematocrit (aka packed cell volume) is the ratio/percentage of red blood cells in the blood. Haematocrit can be reduced because of low RBCs, high plasma, or both.
25
Anaemia
- Give 5 symptoms (what a patient reports)
- Give 4 signs (what you see on examination)
Signs
- Pallor (check conjunctiva)
- Tachypnoea
- Tachycardia
- Hypotension
26
Anaemia - investigations?
27
Give 3 examples of each of microcytic, normocytic and macrocytic anaemia?
28
What is a normal
- WBC
- RBC
- Hb
- Hct (haematocrit)
- MCV
- Platelets
29
What disorder do these bloods show?
What does anisocytosis mean?
What does poikilocytosis mean?
Myelodysplastic syndrome (MDS) aka myelodysplasia
Normocytic anaemia
Failure to produce normal mature RBCs.
Bone marrow biopsy - abnormal cells, maturation arrest. Dysplastic red cells, dysplastic neutrophils, platelet anisocytosis (unequal in size)
Poikilocytosis - different shapes
Normal - reticulocytes, MCV, MCH.
30
What is MCH blood test?
Normal level?
What does it mean if it's high?
What does it indicate if it's low?
MCH = mean corpuscular haemoglobin.
An MCH value refers to the average quantity of haemoglobin present in a single red blood cell.
Normal level = 27-32 pg
Low MCH - iron deficiency anaemia, or thalassaemia.
High MCH scores are commonly a sign of macrocytic anemia. This condition occurs when the blood cells are too big, which can be a result of not having enough vitamin B12 or folic acid in the body.
31
What is aplastic anaemia?
Cause?
What are the signs on blood results? Other test?
Symptoms?
Treatment?
Aplastic anaemia - a normocytic anaemia.
Cause - damage to stem cells in the bone marrow. Autoimmune eg. virus or acquired eg chemotherapy.
Pancytopenia.
Low :
- RBC
- Hb
- Hct
- WBC
- platelets
- reticulocytes
Normal MCV, normal MCH.
Bone marrow biopsy - shows 'empty' bone marrow.
Symptoms
- easy bruising
- easy bleeding eg gums, nose.
Treatment - bone marrow transplant. otherwise fatal.
32
What is haemolysis?
Physical signs of haemolysis?
The premature breakdown of RBC's.
Breakdown of haemoglobin produces bilirubin.
33
What blood results indicate haemolysis?
LDH = lactate dehydrogenase - an enzyme that is raised with increased cell turnover
34
What is LDH?
What is haptoglobin?
LDH = lactate dehydrogenase - an enzyme that is raised with increased cell turnover
Haptoglobin = a protein that binds free haemoglobin. Low levels in haemolysis because its being used up.
35
What do these blood results indicate?
Haemolytic anaemia
- Raised reticulocytes, LDH and bilirubin
- Normocytic anaemia
Spherocytes indicate hereditary spherocytosis, a type of haemolytic anaemia.
NB. HS is autosomal dominant
36
What do these blood results indicate?
Raised reticulocytes, LDH and bilirubin
Anaemia
Bite cells
Haemolytic anaemia
- Raised reticulocytes, LDH and bilirubin
- anaemia
Bite cells indicate G6PD deficiency, a type of haemolytic anaemia.
NB. G6PD is X-linked recessive
37
What is alpha thalassemia trait?
Alpha thalassemia major?
Beta thalassemia trait?
Beta thalassemia major?
38
Describe the conditions of alpha and beta thalassemia major. Which one is worse and always fatal?
39
Describe the conditions of alpha and beta thalassemia trait. What is the usual presentation / concerns?
40
What is the treatment for thalassemia trait and thalassemia major?
41
What do these blood results indicate and why -
Microcytic anaemia
Raised HbA2 (what is this?)
Microcytic anaemia → Beta thalassemia trait.
Mild anaemia.
Raised RBC.
Raised HbA2 (Hb variant with 2 alpha and 2 delta chains)
42
What do these blood results indicate and why?
Alpha thalassemia trait.
Mild microcytic anaemia
Normal RBC
Normal HbA2
43
What is the cause of sickle cell disease?
Single point mutation in the sickle cell gene. Leads to single amino acid substitution. Valine → glutamate in beta chain. Forms HbS.
HbS forms sickle shape when exposed to low oxygen levels.
44
Describe sickle cell TRAIT
What percentage of Hb is HbS?
Care should be taken when?
45
What are the lab findings in sickle cell disease?
How does it present?
Blood film shows?
Chronic haemolytic anaemia from 3-6 months of age
Rate of haemolysis increases during crisis
46
Sickle cell disease - management?
47
What does this blood test show?
Sickle cell TRAIT.
Sickle cell trait - heterozygous for sickle cell gene
HbS accounts for 25-45% if total Hb ('Hb variant 33% in blood result)
48
If blood result shows 'sickle cell variant' at 60% what does that mean?
Sickle cell disease. Hb variant is over 45%.
Hb usually 60-90d/L (worse than in sickle cell trait)
49
What does this blood result mean -
MCV 59. High reticulocytes.
Blood film - target cells and sickle cells.
No HbA (just HbS, HbF, HbA2).
Sickle cell disease 'compound heterozygote'
1 sickle cell gene
1 beta thalassemia gene (absent beta gene) - can't make beta chains - NO HbA (2 alpha 2 beta) there will be just HbS, HbF and raised Hba2.
Severe microcytosis - MCV 59. High reticulocytes.
Blood film - target cells and sickle cells.
50
What is the difference between warm and cold autoimmune haemolytic anaemia?
Which Ig is associated with each?
IgG = warm. Gggggreat its warm!
IgM = cold. Mmmmm its cold :(
51
What is the Coombs test otherwise known as?
What does it test for?
How does it work?
Coombs test = DAT = Direct Antiglobulin Test.
Positive in AIHI (autoimmune haemolytic anaemia)
Patient sample + anti-human Ig = agglutination
52
What is the management for AIHA?
53
What are some causes of haemolysis by mechanical trauma?
54
What does this blood result show?
IgG = warm AIHA.
Low Hb.
High LDH, reticulocytes, bilirubin.
Positive DAT.
Blood film - spherocytes, IgG (cold would show agglutination and IgM)
55
What does this blood test show?
IgM = cold AIHA.
Low Hb.
High LDH, reticulocytes, bilirubin.
Positive DAT.
Blood film - agglutination and IgM (absence of IgG)
56
Name the causes of microcytic anaemia?
What investigations would you do?
NB. Low ferritin points to iron deficiency anaemia
Investigations
- Blood film: microcytic, hypo chromic (central pallor), pencil cells, poikilocytosis (different shaped RBCs)
Thalassaemia - target cells and basophilic stippling
- Dietary intake
- Blood loss eg., menstrual
- Gastro 'top and tail' colonoscopy and OGD
- Haemoglobin electrophoresis (thalassaemia and sickle cell)
57
Name the causes of normocytic anaemia?
What tests would you do?
Tests
- FBC
- Blood film
- DAT / Coombs test (looks for antibodies on red cells, positive in autoimmune haemolytic anaemia or in cases of incorrect blood transfusion)
- Bilirubin (raised in haemolysis)
- LDH (raised in haemolysis)
- Reticulocytes (raised in haemolysis)
- Haptoglobin (low, protein that binds to free Hb so is used up in haemolysis)
58
Name the causes of macrocytic anaemia?
Investigations?
Investigations
- FBC
- Blood film
- B12 and folate levels
- Liver function
- Thyroid function
Myelodysplasia is bone marrow failure
B12 deficiency presents with glossitis and neurological symptoms
59
Group A blood - what antigens on the surface of the RBC? What antibodies in the plasma?
Group B?
Group AB?
Group O?
60
Signs of an acute blood transfusion reaction?
Immediate action to take?
Fever, chills, rigors, tachycardia, hyper or hypotension, collapse, flushing, urticaria, pain, respiratory distress, nausea, malaise.
STOP THE TRANSFUSION and call for help
61
What is the stem cell from which all blood cells are formed?
What are the two lineages called?
Which cells come from each lineage?
Pluripotent haematopoietic stem cell.
Myeloid progenitor cell (7)
- RBC
- Megakaryocte (makes platelets)
- Neutrophil
- Basophil
- Eosinophil
- Monocyte
- Mast cells
Lymphoid progenitor cell (3)
- NK cell
- B cell
- T cell
62
What do monocytes turn into?
What lineage do these cells come from?
Monocytes circulate in the blood, then differentiate into macrophages and dendritic cells which sit in the tissues.
Dendritic cells come from both myeloid and lymphoid lineages
63
What are some alternatives to giving a blood transfusion?
64
What is the difference between conjugated and unconjugated bilirubin? Where do you find them?
65
What is sideroblastic anaemia?
Appearance on blood film?
Symptoms?
Treatment?
Microcytic anaemia.
Normal iron absorption, but can't make the haem.
Results in IRON building up in mitochondria, creating the pathognomic RINGED SIDEROBLASTS.
Build up of iron can cause:
- enlarged liver or spleen
- abnormal heart rhythms
Treatment
- Pyridoxine
- blood transfusions
66
Which disease is associated with the PHILADELPHIA CHROMOSOME?
How does this illness show on a blood test?
Symptoms?
Diagnosis?
Treatment?
CML = chronic myeloid leukaemia. Philadelphia chromosome codes for BCR-ABL, a tyrosine kinase protein which switches on the myeloid lineage.
HIGH NEUTROPHILS (neutrophilia) + myelocytes.
Anaemia symptoms, SPLENOMEGALY, B symptoms
Diagnosis: FBC, blood film, FISH (fluorescent in-situ hybridisation) to look for Philadelphia chromosome. Bone marrow biopsy to asses the phase.
Always TREAT when diagnosed. Treat with TKI - tyrosine kinase inhibitor eg. imatinib. (switches off BCR-ABL).
67
CLL = chronic lymphocytic leukaemia
Usual demographic / course?
How does this illness show on a blood test?
Symptoms?
Diagnosis?
Treatment?
Very high lymphocytes
Usually > 70 yrs. Generally slowly progressive. Involves mature B cell lymphocytes. Often incidental finding and patient is well and doesn't need treatment.
Anaemia symptoms, splenomegaly, lymphadenopathy, thrombocytopenia, B symptoms
FBC (high lymphocytes), blood film (high WBC, mature lymphocytes, smear cells), Immunophenotyping, examination findings.
Treat only if symptomatic. Watch and wait. Monoclonal antibody, chemotherapy, B cell signalling inhibitors (tablets).
No cure.
68
What are the causes of leucocytosis?
69
What are the causes of thrombocytosis?
70
What are the causes of erythrocytosis?
High RBCs.
Primary cause (bone marrow problem) - PV = Polycythaemia vera (JAK2 mutation of red cell precursor)
PV increases risk of THROMBOSIS so should be TREATED
Secondary cause (where the bone marrow is fine but its being stimulated too much ) - chronic hypoxia, doping.
Dehydration can cause APPARENT polycythemia.
71
What are the causes of reduced white cells? Two categories for low counts?
1. Underproduction
2. Reduced survival in the circulation
72
What are the causes of reduced platelets?
73
Causes of low blood counts by reduced production?
1-6 are cancers
Aplastic anaemia - empty bone marrow: stem cell failure, drugs, viruses, pancytopenia.
Haematinic deficiency = B12 and folate
74
What is myeloma?
Myeloma - cancer of plasma cells
75
What is leukaemia?
Name the categories
Cancer of WBC's. Causes over production of one type of cell to the detriment of all others.
76
What is myelodysplasia?
Myelodysplasia - cancer of myeloid cells - causes abnormal/dysfunctional cells
77
What is myelofibrosis?
What can it develop secondary to?
Myelofibrosis - Haematopoietic stem cell cancer. Bone marrow is filled with fibrosis.
Can develop secondary to
- Polycythemia vera
- Essential thrombocythemia
78
What are the four categories of things that leads to high blood counts?
79
What are the causes of hyposplenism?
80
What does the blood film show?
- Three types of cell
- Cause?
Cause : hyposplenism
81
Lymphoma. How might the patient present?
82
What are the features of a high grade lymphoma?
83
What are the features of a low grade lymphoma?
84
What are the stages of lymphoma?
Stage I - 1 site
Stage II - 2 sites, both the same side of the diaphragm
Stage III - There are lymph nodes that contain lymphoma on both sides of the diaphragm.
Stage IV - Multiple sites, both sides of the diaphragm. Stage 4 is the most advanced stage of lymphoma. Lymphoma that has started in the lymph nodes and spread to at least one body organ outside the lymphatic system (for example, the lungs, liver, bone marrow or solid bones) is advanced lymphoma.
B refers to presence of B symptoms
85
How is diagnosis of lymphoma confirmed?
86
What is Burkitt lymphoma?
87
What cell is associated with Hodgkin lymphoma? Describe it
RS cell - Reed-sternberg. Owl eyes. Binucleated cell (two nuclei)
88
Hodgkin lymphoma
- low or high grade?
- Most common in what age groups?
- What gender affected more often?
- Associated with what infection?
- Often presents with a mass where?
- What's the association with alcohol?
- How is it diagnosed?
- Treatment?
- Prognosis good or bad?
.
89
CLL stands for?
Presentation?
Diagnostic tests? What type of cell is raised on an FBC?
Chronic lymphocytic leukaemia
Diagnosis - FBC, blood film, examination findings, immunophenotyping
90
Treatment for CLL?
91
Treatment for CML?
92
How does acute leukaemia present?
- Little bit sick or very sick?
- Long history or short history?
- Symptoms
.
93
How is acute leukaemia diagnosed?
94
What are the treatment options for acute leukaemia?
95
Differences between high grade and low grade lymphoma?
- history, speed of growth, symptomatic, curable, is treatment required, treatment intensity
.
96
What are the stages of haemostasis?
1. Vasoconstriction
2. Formation of platelet plug
- adhesion
- activation
- aggregation
3. Formation of fibrin mesh
4. Clot dissolution
97
What is meant by
- Primary haemostasis?
- Secondary haemostasis?
and what disorders are linked with each stage?
Primary haemostasis - formation of the platelet plug
- Von Willebrand Disease (platelet adherence to collagen requires vWF von Willebrand Factor).
- Low platelets (thrombocytopenia)
Secondary haemostasis - stabilisation of the platelet plug via clotting cascade and deposition of the fibrin mesh.
Disorders include:
- Congenital eg. haemophilia A & B
- Acquired (more common than congenital) eg. warfarin, liver disease
98
What clotting factors are involved in the INTRINSIC pathway of the coagulation cascade?
Why is it called the intrinsic pathway?
Associated disorders?
Measuring method?
INTRINSIC factors XII, XI, IX and VIII (12, 11, 9 & 8).
Called intrinsic as the clotting factors circulate IN the blood vessels.
Haemophilia A & B, factor XII deficiency. IV Heparin.
aPTT
99
What does PT and aPTT stand for? What do they mean?
Does a raised value of 1. PT 2. aPTT increase the risk of bleeding, clotting, or no effect?
PT - prothrombin time.
How quickly the blood forms a clot. Normal is 10-14 seconds.
Raised PT always increases risk of bleeding.
aPTT - activated partial thromboplastin time. Mixed clinical significance - may increase risk of bleeding, clotting, or have no effect.
100
What clotting factors are involved in the EXTRINSIC pathway of the coagulation cascade?
Why is it called the extrinsic pathway?
Associated disorders?
Measuring method?
eXtrinsic - Factors 7 and 3 add to 10.
Extrinsic measures PT. Play Tennis outside!
Extrinsic uses factor 7 and Tissue Factor (TF aka Factor III)
Called extrinsic as tissue factor comes from outside the blood vessels. Tissue factor is released by the tissues when they are injured.
PT (prothrombin time). INR is derived from PT.
DIC, liver disease.
101
What clotting factor is involved in the common pathway of the coagulation cascade?
What is the end result?
10, 10a, 5a, 2 (prothrombin), 2a (thrombin), 1 (fibrinogen), 1a (fibrin)
End result : long fibrin chains stabilise the platelet plug
102
What is fibrinolysis?
X converts Y into Z aka?
Fibrinolysis = breakdown of the fibrin clot by PLASMIN.
Also called the third stage of haemostasis.
Plasminogen → plasmin.
Plasmin converts fibrin → Fibrin degradation products (FDP's) these are also called D-Dimers and are detected on the D-Dimer test.
103
Three things in a coagulation screen?
Which part of the clotting pathway are they measuring?
When are they each abnormal?
104
Bleeding disorders have 4 causes. Name a few for each cause
Blood vessel wall - connective tissue diseases, scurvy (vitamin C), steroids, amyloid.
vWF - Von Willebrand Disease
Platelets - ITP, TTP, bone marrow failure, drugs eg, aspirin, clopidogrel
Coagulation cascade - Haemophilia A (factor VIII), Haemophilia B (factor IX), DIC, liver disease, drugs eg warfarin, heparin, DOACs, massive blood loss.
105
What is TTP?
Cause, symptoms, appearance on blood film, treatment
Thrombotic Thrombocytopenic Purpura. TTP is a rare, life-threatening blood disorder. In TTP, platelet clumps / blood clots form in small blood vessels throughout your body. True medical emergency. Can lead to death in hours if not diagnosed quickly.
Cause - Absent ADAMTS13 → very large vWF → bind platelets in microcirculation causing ischameia in brain, heart, kidney → death.
Causes MAHA - microangiopathic haemolytic anaemia.
Symptoms - Fever, renal impairment, neuro signs, low platelets.
Blood film - shows fragments off RBCs 'cheese wired' cut in half
Treatment - plasma exchange (remove plasma with the multimers)
106
What clotting factors does warfarin affect?
Which pathway of the clotting cascade does it effect?
Antidote?
Warfarin inhibits synthesis of vitamin K dependent clotting facts: 2, 7, 9 and 10. Also protein C and protein S. (competitively antagonises vitamin K).
Affects extrinsic first as factor 7 has shortest half life. common.
Antidotes: Vitamin K (slow), FFP (fast, contains all clotting factors), or PCC (fast, contains factors 2, 7, 9 &10)
107
What are the features and advantages of a DOAC?
Main uses?
(Features are same for thrombin inhibitors and Xa inhibitors)
108
What is a paraprotein?
A monoclonal antibody arising from a clone of lymphocytes or plasma cells.
monoclonal = all making the SAME antibody.
109
What is a paraprotein?
A monoclonal antibody arising from a clone of lymphocytes or plasma cells.
monoclonal = all making the SAME antibody.
Appears as an additional abnormal band on serum protein electrophoresis.
110
Disorders that have a paraprotein? How to tell the difference between the main two?
1. Myeloma - paraprotein plus CRAB symptoms. Bone marrow biopsy will show >10% plasma cells in bone marrow. MRI/PET scan - lytic lesions.
2. MGUS. Monoclonal gammopathy of undetermined significance. Paraprotein ONLY, do not have myeloma, no CRAB symptoms. Bone marrow biopsy will show <10% plasma cells in bone marrow. MRI/PET scan - no lytic lesions.
3. Other - lymphoma, HIV, Hep C, carcinomas, connective tissue disorders, transplant related.
111
What are the clinical features of myeloma?
CRAB
HyperCalcaemia - as a result of bone remodelling. Osteoclasts dissolve/resorb bone.
Renal failure - damage by light chains/ NSAIDs.
Anaemia - renal damage lowers production of EPO
Bone lesions - remodelling
Also
- Infections
- Spinal cord compression (plasmacytomas or fractures, vertebral body collapse)
112
What is myeloma?
What are the three cardinal features?
Myeloma, also known as multiple myeloma, is a cancer / malignant proliferation of the PLASMA cells (plasma cells come from B cells, and make antibodies).
Form of bone marrow cancer.
Accounts for 1% of all cancers. Median age 60-65.
Variable clinical spectrum from asymptomatic → rapid decline and death
113
Myeloma - investigations?
Bone marrow biopsy (shows >10% plasma cells in bone marrow)
Serum paraprotein - mostly IgG. Myeloma does not ALWAYS have a paraprotein, but does usually. (NB. lymphoma is IgM)
Urine = Bence-Jones protein has been superseded by 'serum free light chains'
Blood film may show:
- Rouleux (stacked RBCs like coins) (not diagnostic)
- increased ?
CT/MRI/PET scans may show lytic lesions, vertebral collapse, pathological fractures. (not diagnostic)
114
Myeloma - treatments?
Age > 70 = chemotherapy
Age < 70 = chemotherapy + autologous stem cell transplant (own cells harvested before chemo)
115
Spot diagnosis! What do the following indicate?
1. Target cells
2. Smear cells
3. Hypersegmented neutrophils
4. Philadelphia chromosome
5. Rouleux
6. Reed-Sternberg cells
7. Very high neutrophils
8. Very high leucocytes
9. Bence-jones protein / serum free light chains
10. Serum paraprotein IgG
11. Spherocytes
12. Bite cells
13. DAT /Coombs test positive
14. Howell-Jolly bodies
15. Neurological symptoms
1. Iron deficiency anaemia, thalassaemia, can mean sickle cell disease, liver disease.
2. Leukaemia
3. B12 deficiency
4. CML chronic myeloid leukaemia
5. Myeloma or Waldenstrom's macroglobulinaemia
6. Hodgkin's lymphoma
7. CML chronic myeloid leukaemia
8. CLL chronic lymphocytic leukaemia
9. Myeloma or Waldenstrom's macroglobulinaemia
10. Myeloma
11. Haemolytic anaemia, Hereditary spherocytosis
12. G6PD deficiency
13. Autoimmune haemolytic anaemia, usually.
14. Hyposplenism eg. sickle cell, previous splenectomy, megaloblastic anaemias. HJBs are nuclear remnants - small purple dots.
15. B12 deficiency
116
Spot diagnosis! What do these indicate?
1. Schistocytes
2. Low ferritin
3. Pencil cells
4. Ringed sideroblasts
5. High reticulocytes
6. JAK2 mutation
7. Low haptoglobin
8. Isolated thrombocytopenia
9. Raised HB and raised HCT
10. Raised HbA2
1. Any disease where there is mechanical shearing of RBCs eg. MAHA, DIC, TTP (thrombotic thrombocytopenic purpura), aortic stenosis.
2. Iron deficiency anaemia
3. IDA
4. Sideroblastic anaemia (due to iron building up in mitochondria)
5. Haemolysis
6. Polycythemia vera
7. Haemolysis (haptoglobin is protein that bins to free Hb - used up in haemolysis)
8. ITP - immune thrombocytopenia
9. Polycythemia / erythrocytosis
10. Beta thalassaemia trait
117
What clotting factors are deficient in haemophilia A and B?
Inheritance? Significance? How are sons/daughters of affected men affected?
Signs and symptoms?
Management?
Congenital disorder of secondary haemostasis (clotting factors)
Haemophilia A - factor VIII
Haemophilia B -factor IX.
X Linked Recessive - almost exclusively affects males.
Sons of affected men DONT have the condition
Daughters of affected men are ALWAYS CARRIERS.
Signs and symptoms - Both A and B have variable phenotype - can be mild/moderate/severe.
- Excessive bleeding in response to minor trauma
- Spontaneous haemorrhage without trauma
- neonates can present with intracranial haemorrhage, haematomas and cord bleeding
- Spontaneous bleeding into joints (haemoathrosis) and muscles. If untreated this can lead to joint damage and deformity. 'Target' joints get affected multiple times, becoming weaker each time.
- Bruising
- Retinal bleed
Abnormal bleeding can occur in other areas:
Gums
Gastrointestinal tract
Urinary tract causing haematuria
Retroperitoneal space
Intracranial
Following procedures
Diagnosis -Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing.
Management - blood clotting factor replacement at specialist centres.
Infusions of the affected factor (VIII or IX)
Desmopressin to stimulate the release of von Willebrand Factor
Antifibrinolytics such as tranexamic acid
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What is Von Willebrand disease?
How common is it?
Treatment?
Most common inherited bleeding disorder - affects 1:100 individuals.
Variable severity / phenotype. Results in excessive bleeding eg. periods or after surgical procedures, or in severe types spontaneous bleeds.
Can be autosomal dominant or recessive.
Lack of vWF - von Willebrand Factor promotes adhesion of platelets to damaged endothelium
Often undiagnosed - becomes apparent during surgical procedure or with increasing age
There are 3 main medicines that can help stop bleeds:
- Desmopressin – available as a nasal spray or injection
- Tranexamic acid – available as tablets, a mouthwash or an injection
- Von Willebrand factor concentrate – available as an injection
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What do tear-draped shaped RBC's indicate?
Other name for these cells?
Symptoms of this condition?
Myelofibrosis - usually. Can also be MDS (myelodysplastic syndrome)
Dacrocytes.
Myelofibrosis
- B Symptoms
- Splenomegaly
- Hepatomegaly
- Bone marrow failure eg. infections
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In what conditions do you find schistocytes? (Fragments of RBC's)
Schistocytes are fragments of red blood cells seen in microangiopathic haemolytic anaemia (MAHA).
MAHA may be isolated, or associated with thrombotic microangiopathy syndromes (such as haemolytic uraemic syndrome and thrombotic thrombocytopenia purpura) or disseminated intravascular coagulation (DIC).
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1. Tear-drop poikilocytes
2. Extravascular haemolysis & spherocytosis
3. Middle aged patient + Massive splenomegaly
4. Philadelphia chromosome
5. JAK2 mutation
6. Treatment for haemophilia A a) minor bleeds b) major bleeds
7. Result of alcohol abuse on platelets?
8. Heinz bodies, target cells, basophilic stippling
9. >10% plasma cells in bone marrow
10. <10% plasma cells in bone marrow, with paraprotein
1. Myelofibrosis
2. Warm AIHA
3. CML. Blood film - mature myeloid cells
4. CML
5. Polycythemia (rubra) vera
6. a) Desmopressin b) Recombinant factor VIII
7. Low platelets
8. Thalassemia
9. Myeloma
10. MGUS
