Bloed Flashcards
(112 cards)
1
Q
What does an increased reticulocyte count suggest?
A
1) haemolytic anaemia
2) blood loss
The bone marrow is working hard to replace the lost cells and is releasing immature cells
2
Q
Name 3 causes of microcytic anaemia
A
“SIT”
Sideroblastic anaemia
Iron deficiency anaemia
Thalassaemias
3
Q
Name 3 causes of normocytic anaemia
A
acute blood loss
anaemia of chronic disease
sickle cell anaemia
4
Q
Name 4 causes of macrocytic anaemia
A
remember: FAT RBC
F = folate deficiency A = alcohol T = thyroid (hypothyroidism)
R = reticulocytosis B = B12 deficiency C = cytotoxic drugs
5
Q
Name 3 causes of IDA
A
Chronic blood loss (menstrual, GI (high urea))
Malabsorption (coeliac’s disease, gastrectomy)
Increased demand (pregnancy, growth)
6
Q
What lab results would you expect in haemolytic anaemia?
A
elevated unconjugated bilirubin
elevated LDH (from RBC)
increased reticulocyte count
7
Q
What would you check in iron studies?
A
Iron
transferrin
total iron binding capacity
ferritin
8
Q
Name the haematinics
A
B12
folate
ferritin
9
Q
What is polycythaemia?
A
Increased concentration of Hb within the blood
10
Q
What are causes of polycythaemia?
A
Relative polycythaemia: (decreased plasma volume)
-acute dehydration
Absolute polycythaemia: (increased RBC mass)
- polycythaemia ruba vera (primary)
- raised EPO or chronic hypoxia (secondary)
11
Q
Causes of thrombocytopaenia
A
1) decreased production
- bone marrow failure
- aplastic anaemia
- megaloblastic anaymia
2) increased destruction/consumption:
- DIC/TTP/HUS
- ITP
- SLE/CLL
- drug induced
12
Q
WBC differential
A
determines the number of polymorphs, lymphocytes and monocytes in the total WCC
13
Q
Which conditions cause hypochromic microcytic RBC?
A
poorly haemoglobinised and small (reduced MCH/MCV)
1) IDA
2) ACD
3) thalassaemia
14
Q
MCV
A
mean corpuscular volume = RBC size
15
Q
MCH
A
Mean corpuscular Hb content
16
Q
Reticulocytes
A
Immature RBC
Usually <2% of RBC
No nucleus but some persisting RNA
polychromatic appearance on blood film
17
Q
Name two conditions in which you would see spherocytes
A
AIHA
hereditary spherocytosis
18
Q
Howell-Jolly bodies
A
nuclear fragments in RBC
Seen in hyposplenic patients
19
Q
In which condition would you see macrocytes?
A
Large RBC (increased MCV)
B12/folate deficiency
hepatic disease
hypothyroidism
20
Q
What is anisopoiklocytosis and when would you see it?
A
variation in size (anisocytosis) and shape (poiklocytosis) of RBC.
Seen in B12/folate deficiency
21
Q
When would you see RBC fragmentation?
A
In mechanical haemolytic anaemias (e.g. prosthetic valve malfunction)
22
Q
When would the direct coombs test be positive?
A
test to detect the presence of an antibody on the RBC surface
positive in AIHA and HDN
23
Q
What are leukaemic blasts and when would you expect to see them?
A
abnormal primitive blast cells that are found in the bone marrow and sometimes the peripheral blood.
Seen in acute leukaemia and poor prognosis myelodysplastic syndromes
24
Q
What are myelodysplastic syndromes?
A
Characterised by dysplasia and ineffective haemopoieisis in 1 or more of the myeloid cells.
Characterised by progressive bone marrow failure. Peesent with fatigue/infections/bleeding.
May be associated with monosomy 7 (loss of a chromosome)
Can progress to secondary AML
25
Myeloproliferative disorders
Describes proliferation of cells in the bone marrow with normal (non-dysplastic) appearance.
CML
Polycythaemia Vera
Essential thrombocythaemia
Myelofibrosis
26
Myeloma
malignant prolfieration of plasma cells in the bone marrow
27
What kind of disorder is myeloma?
a lymphoproliferatice disease
28
What is PT and what does it assess?
Prothrombin time
Test of the extrinsic pathway of coagulation
Sensitive to warfarin
29
What is INR?
International normalised ratio
Measure of warfarin activity
30
What is PTT?
= APTT
Partial thromboplastin time
Measure of the intrinsic pathway of coagulation
Sensitive to IV heparin
31
What is a group and screen?
determines ABO and Rh group
Screens plasma for immune RBC antibodies
32
What are packed RBC?
units of blood from which plasma has been removed
33
What is cryoprecipitate?
prepared from donated plasma
rich in factor VIII and fibrinogen
34
What is the indirect coombs test?
a test used to detect the presence of RBC antibodies in plasma.
Forms the basis of the Cross match and the antibody screen in group and screen.
35
Which cells are derived from lymphoid progenitor cells?
B cells
T cells
NK cells
36
where is EPO mainly produced?
peritubular interstitial cells of the kidneys
Liver in newborns (less sensitive than the kidneys to hypoxia, so newborns have a smaller EPO response)
37
Where is TPO produced?
the liver
38
Which cytokines stimulate WBC formation?
IL-7 stimulates lymphoid progenitor cell line (7 upside down is like an L)
IL-3 stimulates myeloid cell line (3 on its side looks like an m)
39
What is anaemia?
Haemoglobin concentration below the reference range for age and sex
40
What is pernicious anaemia?
Insufficient haemopoieisis due to an inability of parietal cells to produce intrinsic factor, which is required for B12 absorption
Antibody against intrinsic factor
41
What is aplastic anaemia?
Rare condition in which there is destruction of red bone marrow and haematopoeitic stem cells.
Causes pancytopaenia = anaemia + leukopaenia + thrombocytopaenia
Caused by toxins, gamma radiation and drugs.
42
Signs and symptoms of anaemia
SOB
pallor
fatigue
jaundice in haemolytic forms
43
Where are HSC found?
Bone marrow
Umbilical cord blood
peripheral blood after stimulation with G-CSF
44
What are bone marrow stromal cells and what is their role?
Macrophages, fibroblasts, fat cells, endothelial cells and reticulum cels
Stromal cells form the bone marrow microenvironment that supports developing HSC. They have adhesion molecules which retain developing cells in the bone marrow
They secrete extracellular matrix molecules (collagen, fibronectin, laminin and proteoglycans) and growth factors.
Provides the requirements of the stem cell for growth and division
45
Clonal HSC disorders
haematological malignancies arising from a single ancestral cell
NB: in contrast, nonmalignant proliferations are polyclonal
46
Name 3 myeloproliferative disorders
1) polycythaemia ruba vera (PRV)
2) Essential thrombocytosis
3) myelofibrosis - marrow filled with fibrous tissue, so liver and spleen take over blood cell production
Can transform into AML
47
Essential thrombocytosis
overproduction of platelets
Associated with Jak2 and calreticulin mutations
Clumps of platelets seen in peripheral blood
Platelets produced are non-functional, so haemorrhage may occur
Treat with aspirin and mild chemotherapy (severe cases)
Can use JAK2 inhibitors (ruxolitinib)
48
Refractory anaemia
Group of anaemic conditions not associated with any other disease; characterised by a frequently advanced anaemia that can only be successfully treated by blood transfusions.
Associated with monosomy 7
may have excess blasts (risk of progressing to CML)
49
Fanconi anaemia
Most common inherited form of aplastic anaemia. Causes pancytopaenia.
Autosomal recessive. faulty FANC gene
Much of the bone marrow becomes replaced by fat.
Other abnormalities:
- cafe au lait spots
- hearing loss
- micropthalmia
- GI/GU malformations
Requires allogeneic SCT
50
What are the main indications for SCT?
relapsed Hodgkin's disease
non-Hodgkins lymphoma
Myeloma
51
What does increased serum ferritin suggest?
Can suggest iron overload
However, ferritin is an acute phase reactant, so it will be elevated in tissue inflammation/infection damage as well. (IDA can occur with normal serum ferritin in the presence of tissue inflammation)
Therefore elevated ferritin does not necessarily suggest iron overload
52
What is latent IDA?
low serum ferritin and normal haemoglobin
Erythroblasts take what iron is available in stores to maintain normal Hb levels
53
Clinical presentation of IDA
koilonychia
atrophic glossitis (pale, smooth, painless tongue)
Angular stomaitis
54
Anaemia of chronic disease
Form of anaemia seen in chronic infection, chronic immune activation and malignancy
Normal or increased iron stores but decreased amounts in serum. Inflammation can prevent the body from using stored iron (failure of iron utilisation)
```
Low iron
Low TIBC
N/increased ferritin
increased ESR
N/low MCV/MCH
```
55
What form of anaemia is associated with a painful tongue and subacute demyelination of the spinal cord?
vitamin B12/folate deficiency = megaloblastic anaemia
Bilateral peripheral neuropathy
mild jaundice
megaloblastic anaemia
56
Haemolytic anaemia
anaemia related to reduced RBC lifespan
no blood loss
no haematinic deficiency
57
What are the lab findings in compensated haemolytic anaemia?
normal Hb
elevated reticulocyte count
elevated unconjugated bilirubin
58
Congenital haemolytic anaemias
1) abnormalities of RBC membrane = hereditary spherocytosis (AD)
2) haemoglobinopathies
3) abnormalities of RBC enzymes = Pyruvate Kinase Deficiency Anaemia (AR) or G6P dehydrogenase deficiency (XLR)
59
Causes of acquired haemolytic anaemia
1) autoimmune - warm AIHA (IgG) / cold AIHA (IgM)
2) isoimmune - haemolytic disease of the newborn
3) fragmentation - haemolytic uraemic syndrome or valve malfunction
60
Cold AIHA (autoimmune hemolytic anemia)
IgM autoantibody
Causes RBC agglutination
Seen in infections (e.g. mycoplasma)
Difficult to treat. Keep warm.
61
Warm AIHA (autoimmune hemolytic anemia)
more common than cold AIHA
IgG autoantibody
seen in context of other autoimmune diseases - SLE, RA.
May be drug-induced.
Stop causative drugs and give steroids / immunosuppressants. Splenectomy if all else fails
62
Mechanisms of Drug Induced AIHA
1) acting as a hapten - binds to RBC and stimulates antibody formation
2) immune complex formation - antibodies form to drug and RBC are caught in the crossfire
3) autoimmune - drug can stimulate immune system to attack RBC (rare)
63
Name 3 inherited bleeding disorders
1) haemophilia (A = factor VIII, B = factor IX)
2) von Willebrand disease
3) severe platelet disorders
64
Name 3 acquired bleeding disorders
1) DIC
2) coagulopathy in liver disease (alcohol)/vitamin K deficiency
3) complication of warfarin therapy
65
Name 3 inherited thrombotic disorders
1) thrombophilia
2) Factor V Leiden
3) prothrombin gene mutation
66
Name an acquired thrombotic disorder
1) antiphospholipid syndrome
67
What does mucocutaneous bleeding suggest?
platelet disorder
68
What does bleeding into a potential space (e.g. haemarthrosis) suggest?
Coagulation defect
69
What does easy bruising since childhood suggest?
an inherited cause of the bleeding disorder
70
What are the functions of von Willebrand factor?
1) facilitated platelet adhesion and aggregation (binds collagen and platelet glycoproteins)
2) prolongs half-life of factor VIII
71
What lab findings would you expect in DIC?
```
prolonged PT
prolonged APTT
schistocytes on blood film
thrombocytopaenia
elevated d-dimer
```
72
Treatment of DIC
aggressively treat underlying cause
Give FFP and platelets
73
Bleeding complications with warfarin
increased risk of brain haemorrhage (elevated INR)
74
Management of elevated INR
Stop warfarin (if life-threatening bleeding) or reduce dose
Give Vitamin K (oral takes 24 hours, IV takes 6 hours)
Give coagulation factors II, VII, IX and X -> Beriplex (takes 20 minutes)
75
What is the effect of Desmopressin (DDVAP) in management of bleeding disorders?
increases the concentration of von willebrand factor and factor VIII
76
What lab results would you expect for factor VII deficiency?
prolonged PT, normal APTT
77
What lab results would you expect for a factor XII deficiency?
Normal PT, prolonged APTT
78
What lab results would you expect for haemophilia?
Normal PT, prolonged APTT
79
What lab results would you expect for von willebrand's disease?
Normal PT, prolonged APTT (vWF prevents degradation of factor VIII)
80
What is PT and how is it assessed?
Prothrombin time, assesses the function of the extrinsic pathway
Add Thromboplastin to patient's plasmin and add calcium. Measure time to clot
NB: INR = standardised form of PT
81
What is aPTT and how is it assessed?
Activated partial thromboplastin time (APTT) assesses the function of the intrinsic pathway.
```
Add:
Patient’s plasma
Contact factor
Phospholipid
Calcium
```
Measure time to clot
82
What is TCT and how is it assessed?
Thrombin Clotting Time (TCT)
Measurement of conversion of fibrinogen to fibrin clot. Indicates how much functioning fibrinogen is in the patient’s blood (common pathway)
Add excess thrombin
83
What is the impact of Lupus anticoagulant on the coagulation screen?
Causes prolonged APPT
84
Which drug provides immediate but short-acting anticoagulant effects?
heparin
85
which anticoagulant drug is safe to use in pregnancy?
heparin
86
Mechanism of action of warfarin
Blocks reduction of vitamin K, which is required as a cofactor for the synthesis of factors II, VII, IX and X
Results in decreased prothrombin levels
NB: has delayed onset and offset. Therefore NOT used for immediate anticoagulation or short term thromboprophylaxis
87
Which drug would you use for immediate anticoagulation or short term thromboprophylaxis?
Heparin. DOACs are also active immediately
Must start with heparin therapy before initiating warfarin (because of the delayed onset of warfarin as the existing pool of functional clotting factors has to be replaced by dysfunctional factors)
88
Which bacteria is Streptokinase isolated from?
group C haemolytic streptococci bacteria
Causes systemic plasmin activation
89
Uses of Fibrinolytics
```
used IV or intra-arterially to treat:
o Venous thrombosis
o Myocardial infarction (within 12h)
o Thrombotic stroke (within 4.5h)
o massive PE
```
90
Mechanism of action: Clopidogrel
blocks platelet ADP receptor, preventing aggregation
91
Mechanism of action: aspirin
irreversibly inhibits COX in platelets. This prevents production of thromboxane A2, preventing platelet activation/aggregation
92
Mechanism of action: Dipyridamole
prevents platelet activation/aggregation by increasing cAMP, thereby reducing responsiveness to ADP stimulation
93
What are the risks of splenectomy?
infection with encapsulated microorganisms:
- streptococcus pneumoniae
- haemophilus influezae
- neisseria meningitidis
94
What prophylactic measures should be taken with splenectomy?
vaccination
prophylactic antibiotic therapy (penicillin V)
carry a splenectomy card
95
What is immunophenotyping and why is it done?
used to determine cell nature (lymphoid vs myeloid)
Done using monoclonal antibodies to surface or intracellular markers.
done on blood/bone marrow samples
methods:
1) flow cytometry
2) immunocytochemistry
96
Causes of pancytopaenia
1) bone marrow failure
2) hypersplenism
3) peripheral consumption of blood cells
97
When would you find normal blast cells in peripheral blood?
cancer metastases to bone
severe infection
radiotherapy for cervical cancer can cause bone marrow scarring
98
What is leucoerythroblastic anaemia?
anaemia due to a space occupying lesion of the bone marrow
99
What investigations would you perform in a patient with suspected acute leukaemia?
FBC/blood film
bone marrow examination:
- microscopy
- immunophenotyping
- cytogenetics to check for a chromosomal translocation
100
What is a bone marrow transplant?
transplantation of multipotent HSC (from bone marrow/peripheral blood/umbilical cord blood)
A means of replacing malignant cells with normal stem cells
the patient must be conditioned before (put into full remission)
101
Idiopathic thrombocytopaenic purpura
isolated thrombocytopaenia
purpuric rash and tendency to bleed
diagnosis of exclusion (e.g. not secondary to SLE/RA)
no splenomegaly --> splenomegaly excludes a diagnosis of ITP
102
Infectious mononucleosis
caused by EBV
fever, sore throat, cervical lymphadenopathy, fatigue
atypical mononuclear cells
do NOT give amoxicillin - will cause a rash. Give penicillin V instead
103
How do you test for infectious mononucleosis?
Monospot test (IM produces heterophile antibodies)
104
does lupus anticoagulant predispose to thrombosis or bleeding?
in vitro - anticoagulant effect. Prolongs APTT (not corrected by addition of normal plasma)
in vivo - thrombotic tendency
105
What system is used to stage lymphoma?
Ann-Arbor
106
What are the stages of Ann-Arbor for lymphoma?
Stage I - single group of lymph nodes
Stage II - more than one group of lymph nodes on the same side of the diaphragm
Stage III - groups of lymph nodes affected on both sides of the diaphragm (includes spleen)
Stage IV - extranodal involvement
A - no B symptoms
B - B symptoms
107
What kind of lymphoma is seen more often in older patients?
Non-Hodgkin's Lymphoma
108
Give 4 examples of intravascular haemolysis
1) RBC fragmentation syndromes
2) ABO incompatible blood transfusion
3) cold type AIHA
4) malaria
109
What are the main laboratory findings in intravascular haemolysis?
* Anaemia, reticulocytosis and raised unconjugated bilirubin
* Haemoglobinaemia and haemoglobinuria
* Haemosiderinuria
free Hb saturates plasma haptoglobin (a binding protein).
Excess free Hb in the plasma is filtered at
the glomerulus leading to haemoglobinuria.
The renal tubules reabsorb some Hb from the urine.
This is broken down to form haemosiderin which can also appear in the urine.
110
What type of haemolysis is caused by warm AIHA?
Extravascular
The IgG attaches to the red cell antigen and damages the RBC membrane. The damaged RBCs become
spherocytic and are phagocytosed by the RES, particularly the spleen.
111
Which unusual sites can be infiltrated in ALL?
CSF and testicles
112
D-dimer
fibrin degradation product
o a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis
o elevated D-dimer levels = due to high fibrinolytic activity
NB: high d-dimer level common in patients who abuse alcohol (poor clearance of activated coagulation factors)
