Haematology - Part 1 Flashcards
1
Q
Describe what happens on each day of the origins of haemopoiesis
A
Day 27 - starts in the aorta-gonado-mesonephros region
Day 35 - expands rapidly
Day 40 - migrates to the liver which becomes the main site of haemopoiesis
2
Q
Name Myeloid cells
A
Granulocytes, erythrocytes, platelets
3
Q
Name lymphoid cells
A
lymphocytes
4
Q
RBC life span
A
120 days
5
Q
Most common cell type in blood
A
Neutrophils
6
Q
Increased in bacterial infections
A
neutrophils
7
Q
Increased in parasites and allergies e.g. aspirin
A
eosinophils
8
Q
Basophilia indicates
A
chronic myeloid leukeamia
9
Q
life span of neutrophils
A
6-8 hours
10
Q
Name of monocytes in the liver and skin
A
Kuppfer cells in liver, langerhans cells in skin
11
Q
What does monocytosis indicate
A
TB
12
Q
Causes of lymphocytosis
A
atypical lymphocytes of glandular fever (usually self limiting) or chronic lymphocytic leukaemia
13
Q
Causes of lymphopenia
A
3 months post bone marrow transplant
14
Q
What is myeloma
A
the malignant overproduction of plasma cells
15
Q
What do we collect blood into
A
into EDTA anti coagulated tubes
16
Q
Where do we take a bone marrow aspirate from
A
liquid bone marrow aspirate from the posterior iliac crest. Treptine core biopsy is also taken
17
Q
What is sensitivity?
A
Proportion of abnormal results correctly identified by the test,
18
Q
What is specificity?
A
The proportion of normal results correctly classified by the test
19
Q
What could cause a false result of thrombocytopenia?
A
Platelets clotting in the tube
20
Q
What happens to lymphocyte count post splenectomy
A
Mild lymphocytosis
21
Q
Causes of microcytic anaemia
A
Iron defeciency, chronic disease, thalassaemia, lead poisoning, sideroblastic anaemia
22
Q
Normocytic anaemia causes
A
Blood loss, haemolytic, chronic disease, bone marrow failure (post chemo or due to infiltration by carcinoma)
23
Q
Macrocytic anaemia causes
A
Megaloblastic –> B12 or folate defeciency –> get hypersegmented neutrophils and oval microcytes
Non-megaloblastic –> alcohol (most common cause), liver disease, myelodysplasia and aplastic anaemia).
24
Q
Ranges for anaemia types
A
Microcytic: MCV 27pg
Macrocytic: MV: >95
25
What does leucodepletion do?
Separates RBC from the whole blood
26
What can plasma be split into?
Fresh frozen plasma (FFP), cyroprecipitate or fractionation into factor concentrates and immunoglobulins
27
What do we replace plasma with in RBC storage
glycose, electrolyes and adenine to keep RBC healthy
28
What is the transfusion threshold trigger
The lowest haemoglobin concentration not associated with anaemia symptoms
29
How do we adapt to anaemia
Increase cardiac output, increase cardiac artery blood flow, increase Epo, Increase 2,3 DPG
30
Thresholds for transfusion
31
What do we do for patients on regular transfusion due to inherited anaemias?
Suppress endogenous Epo
| Beware of Iron overload can cause cardiomyopathy and liver failures
32
When do we give FFP?
Massive haemorrhages, coagulopathy with bleeding/surgery, thrombotic thrombocytopenia purport
DO NOT GIVE to reverse warfarin or to replace single factor
33
What is crossmatching
mixing the donor RBC with the patients plasma to see if a reaction occurs
34
Acute Transfusion Reactions
Immune: Acute haemolytic reaction, allergic reaction, TRALI
| Non-immune --> bacteria, contamination, TACO, febrilenon-haemolytic transfuion reaction
35
Delayed transfuion reaction
Immune: TA GVHD, Post transfusion Purpura
| Non-immune: TTI
36
Acute haemolytic Reaction summary
Release of free Hb --> renal failure, microvascular thrombosis, cytokine storm, vasoconstriction
37
What may be the first sign of acute haemolytic reaction in anaesthetised patients?
Haemoglobinuria
38
Signs of acute haemolytic reactions
fever/chills, back pina, infusion pain, haemoglobinuria, bleeding, chest pain
Fatal in 15-20% of people
39
What causes delayed haemolytic reactions
Develop antibodies to RBC antigens other than ABO Post transfusion
Get fatigue, jaundice, increased bilirubin/LDH, decreased Hb, fever
40
What is TRALI?
Where the donors plasma has antibodies against the recipients leucocytes (anti-HLA, anti-HNA).
Activated WBC lodge in the pulmonary capillaries --> release substances causing endothelial damage
Fever, hypotension, DO NOT GIVE DIURETICS OR STEROIDS, fluid loading improces
Fatal in 5-10% of people
41
What is TACO?
Get sudden dyspnoea, orthopnea, tachycardia, hypertension, hyperaemia, increased JVP
Risk factors are the elderly, small children, reduced LV function, fast transfusion or high volume
42
What is urticarial rash
May occur with a wheeze, occurs due to hypersensitivity to a random plasma protein
43
What is anaphylaxis
Severe life threatening reaction soon after transfusion starts, wheeze, tachcardic, hypotension, laryngeal/facial oedema
44
What causes febrile non-haemolytic anaemia
Due to the accumulation of cytokines during blood storage
Unpleasant but not fatal
Occurs during or soon after reaction. Get a fever and go tachycardic
45
What do we give to treat thrombotic stokes?
Anti-platelets
46
How does a haemostatic plug form
Damage to the vessel wall, platelets adhere via vWF --> platelets activate and clump together to form clot
47
What is thromboxane
Produced by platelets (using COX enzyme) --> causes the constriction of vessel walls
48
What blocks the COX enzyme
Aspirin inhibits COX irreversibly (whereas the other NSAIDS are reversible) and inhibits COX1 more than COX2
49
What receptor binds fibrin for aggregation
Glycoprotein alpha2-beta3
50
What does clopidogrel black
The ADP receptor as ADP activates platelets
51
What pathway is the intrinsic pathway
12,11,9,7 - APTT
| Factor 12 activates when in contact with a foreign surface (i.e. silica)
52
Extrinsic pathway
Prothrombin time --> F7 and TF. Tissue factor is expressed on the surface of damaged cells
53
What factor does thrombin activate?
Factor 11. Hence Factor 12 deficiency is asymptomatic, factor 11 deficiency has varying symptoms
54
Name the anticoagulatns
Protein C ( and its cofactor protein S), antithrombin III, fibrinolytic syndrome
55
What does protein C cleave?
Factor V
56
What enzyme mops up plasmin
alpha2-antiplasmin
57
What bleeds do platelet/vessel wall defects cause?
```
Mucosal and skin bleeding
Superficial bruising
Petechiae (not palpable and don't blanch)
Spontaneous
Prolonged and non-recurrent
```
58
What types of bleed do coagulation defects cause?
```
Joint bleeds
Deep spreading haematomas
Retroperitoneal bleeds
Deep muscular bleeds
Prolonged and recurrent
```
59
Causes of vessel wall//platelet defects
thrombocytopenia, abnormalities in platelets, abrnormal vessel wall (Ehlers Danlos and Scurvy), Abnormal reaction between platelets and vessel wall (e.g. vWF)
60
What is vWF
A large multimeric protein with lots of subunits
vWF disease is the most commonly inherited bleeding disorder
61
Which part of vWF is good for adhesion
the high molecular weight part
62
Which blood group have lower levels of vWF
blood group O
63
What are the types of vWF
Type 1 - reduced amount of normal vWF
Type 2 - abnormal vWF but normal amount (only have low molecular weight part)
Type 3 - severe
64
type of inheritance for vWF
type 1 & 2 are autosomal dominant
| Type 3 is autosomal recessive!!
65
What does vWF carry?
Factor VIII, hence defeciencies cause coagulation problems too. In types 1 & 2 it may also cause low FVIII especially in women
66
Symptoms of vWF disease?
mucocutaneous bleeding including menorrhagia, post op+ post partum bleeding
67
Treatment of vWF
```
Antifibrinolytics (tranaexmic acid)
DDAVP --> releases vWF from endothelial cells --> can be tolerant after 3rd time
Factor concentrates of vWF
COCP for menorrhagia
Recombinant vWF in trials
```
68
Who do we not give DDAVP too?
Under 2's as it acts as a vasoconstrictor like vasopressin
69
What do we do before giving factor concentrates?
Ensure they are vaccinated against hepatitis
70
What inheritance are the haemophililas
X-linked recessive
71
What is haemophilia A
Factor VIII defeciency 1in 5000 males
72
What is haemophilia B
Factor IX defeciency 1 in 30000 males
73
What types of bleed are the haemophilia?
muscle haemorraghes (can cause limb deformities), haemarthrosis, risk of intracranial bleed during pregnancy, spontaneous and severe,
74
Treatment of Haemophilia
Replace protein
Factor concentrates
Antifibrinolytics
Vaccine against hepatitis
75
What do we give only to treat haemophilia A
DDAVP as it releases vWF which carries factor VIII
76
What can stop factor concentrates working?
Inhibitor development in 25% of haemophilia A (more common than in B). Mostly occurs in early treatment (first 10 days) and there is a genetic predisposition.
Give very high levels of Factor 8 so the body doesn't see it as foreign
77
How do you distinguish between inhibitor or deficiency?
repeat test with 50:50 normal to patients blood. If inhibitor APTT remains the same, if defeciency APTT improves
78
What pathway does APTT measure?
Intrinsic
79
What pathway does prothrombin time measure?
Extrinsic
80
Where are the coagulation factors made?
All in the liver hepatocytes except Factor VIII made in the Kuppfer cells
81
Reasons for Vitamin K Defeciency
Nutritional defeciency
Obstructive jaundice
Broad spectrum antibiotics (kill off the bacteria in the gut that synthesise vitamin K)
Neonates for 1-7 days --> give vitamin K injections to prevent this
82
What factors are vitamin K dependent?
2, 7, 9, 10
83
Describe changes in coagulation in liver disease
Thrombocytopenia --> due to portal hypertension and splenic congestion
Plateley dysfunction --> abnormal platelets as plasmin cleaves surface glycoproteins
Excess plasmin activity
Reduced factor concentration except for factor VIII
Delayed fibrin monomerisation due to altered finbrin glycosylation (as a result of excess silica acid)
84
What defines a massive transfsion
Transfusion patients total body blood volume in 24 hours or 50% in 3 hours
85
Complications of massive transfusions
DIC is common
Dilutional depletion of platelets and coagulation factors
- mainly factors V, VIII and fibrinogen
- need at least 7-8 litres of transfusino to cause thrombocytopenia in adults
Citrate toxicity (rare but if hypothermic or neonate risk increased)
Hypocalcaemia --> but no clinical significance
86
Describe DIC
inappropraite activation of clotting and secondary fibrinolytic syndrome
Bleeding and small vessel thrombosis occurs, microvascular thrombosis causes end organ damage and microangiopathic haemolysis
87
Acute causes of DIC
Sepsis, obstetric complications, trauma/tissue necrosis, acute intravascular haemolysis, fulminant liver disease
88
Chronic causes of DIC
Obstetrics (retained dead foetus), malignancy, end stage liver disease, severe localised intravascular coagulation
89
Diagnosis of DIC
Prolonged APTT & PT, raised D-dimer levels
| No one diagnostic test
90
Treatment of DIC
Treat underlying cause, supportive measures
91
How do we control doses of oral anticoagulants
INR = (prothrombin time)^ISI
Prothrombin time = patients prothrombin time/normal
ISI = correction factor for sensitivity of thromboplastic to the international reference
92
What drugs potentiate warfarin
```
Erythromycin
NSAIDS
Cephalosporins
Sulphanylureas
Corticosteroids
Ampicillin
Amiodarone
```
93
What drugs potentiate warfarin
Cholestyramine, spirinalactone, Rifampicin, Carbamazepine, Vitamin K
94
How do we measure effects of heparin
Mainly use APTT (But doesn't measure LMWH)
- measure is effects on anti-thrombin and Xa
- can use calcium prothrombin time or anti Xa Assays (does measure LMWH hepatic time)
95
How to treat over coagulation with heparin
consider protamine
96
LMWH acts most on which factorq
Higher ration of Xa than IIa activity. Higher bioavailability, longer half life and also more predicatable anti-coagulant response
97
What do we give as supportive if long term DIC
Folic acid and vitamin K
98
When is Epo produced
produced by the kidneys in response to hypoxia
99
What does the globin chain do in haemoglobin
keeps it soluble, protects it from oxidation, allows for varying oxygen affinities
100
What chromosome is alpha for Hb on
Chromosome 16
101
What chromosome are the other Hb chains on
all the other Hb chains are on chromosome 11
102
Describe normal adult Hb
Hb-A 95% (alpha, alpha) Hb-A2 3.5% (alpha, delta) HbF 1% (alpha, F)
103
What are haemoglobinopathies
changes in globin genes or their expression that causes disease.
Either structural or thalassaemia
104
What is a thalassaemia
changes in gene expression: imbalance of normal alpha and beta chain production
FREE GLOBIN DAMAGES THE RBC CELL MEMBRANE
105
How to diagnose haemoglobinopathis
Hb Electrophoresis (but doesn't pick up thalassaemias)
Isolectric Focusing
High Performance Liquid Chromatography
106
Describe the sickle cell mutation
Valine to Glutamine substitution at position 6 of the beta globin gene on chromosome 11
107
What happens in sickle cell disease
HbS polymersises at low oxygen to form long fibrils, distort the cells membrane causing a sickle cell shape
Reduces RBC life span to 20 days --> haemolytic anaemia
108
What can reduce the effect of haemoglobinopathies
If there are other haemoglobin types in the blood i.e. HbF
| HbF persists for 6 months after birth and can hide the effects of sickle cell
109
Where do sickle cells occlude
Post capillary vessels as they cause an inflammatory response
110
Symptoms of sickle cell trait
no clinical problems except with dehydration/severe hypoxia
111
Where is sickle cell disease most common
West Africa
112
Acute complications of sickle cell disease
Vado-Occlusive crises: bone, brain, dactyitis, priapism, chest syndrome
Septicaemia
Aplastic Crisis
Sequestration crisis (enlargement of spleen and liver)
113
What do we give to prevent septicaemia in sickle cell
prophylactic penicllin
114
Chronic complications of sickle cell
```
Hyposplenism
Renal disease (medullary infarct, papillary necrosis, tubule damage --> inability to concentrate urine)
Avascular necrosis
Leg ulcers
Respiratory and cardiac complications
Gall stones
Osteomylitis
Retinopathies
```
115
How do we treat sickle cell
Penicillin, analgesia, ECHO screen, transfusion (reduces risk of stroke), hydroxycarbamide
Bone marrow transplant is the only cure
116
What does hydroxycarbamide do?
Treats sickle cell anaemia --> reduces the adhesion to the endothelium and enhances NO (a vasodilator)
117
Name the types of alpha thalassaemia
```
Hb Barts (alpha0) --> hydrops fetalis
HbH --> Tetramer of beta globin, soluble but not very functional
```
118
What is beta thalassaemia
reduced rate of production of beta globin genes pathologically caused by the excessive production of alpha genes
119
Describe thalassaemia minor
blood resembles iron deficiency
| no clinical implciations
120
Describe problems in thalassaemia intermedia
Pulmonary hypertension --> do an ECHO scan
Leg Ulcers
Hormone/endocrine problems (diabetes due to Fe deposits in endocrine organs and hypothyroidism)
Bone changes --> do a DEXA scan
Extramedullary haematopoiesis
No requirement for transfusion in first 3-5 years of life unless not meeting development foals
121
Describe thalassaemia major problems
Presents at 1-2 years
Short stature and distorted limbs due to premature closing of the growth epiphysis
Blood transfusios in life saving
Abnormal lots of nucleated RBC --> as the bone marrow is pumping reticulocytes
122
Describe the pathology of thalassaemia major
Excess alpha chains (due to ineffecetive erythropoieisis and reduced life spain)
Increased bone marrow activity (causes skeletal deformity, increases iron absoprption and end organ damage, protein malnutrition (transfusion can exacerbate organ damage)
Enlarged and overactive spleen due to pooling of RBC
123
Describe thalassaemia facies features
Maxillary hypertrophy
Abnormal dentition
Hair on end skull as diplopic cavities widened by expanding bone marrow
Frontol bossing due to expanding bone marrow
124
Treatment of thalassaemia major
Transfusion every 3 to 4 weeks: Problem is no system to excrete iron from the body causing iron overload
125
Problems of iron overload
Dilated cardiomyopathy/heart failure, liver cirrhosis, failure of puberty/growth, diabetes
126
Common causes of death in thalassaemia major
cardiac failure, arrhythmia and infections
127
How to Treat Iron Overload
Iron chelation therapy from 2nd year of life --> promotes the excretion of iron in faeces and urine
Hormone replacement of hypogonadism
Good iron chelation makes you fertile but the stress of pregnany on the weak heart from iron overload is bad
128
Examples of iron chelators
Desforrioxamine
New oral iron chelators are deferipone and deferasirox
129
Describe changes physiological anaemia in pregnancy
Plasma volume expands 50%, RBC mass expands 25% --> hence haemodilution max at 32 weeks.
causes physiological anaemia
130
Describe what happens to leucocytes in pregancy
Get leucocytosis as the placenta secretes GCSF causing the bone marrow to produce more WBCS
Mainly neutrophilic from the 2nd month to peak in 2nd/3rd trimester
131
When does neutrophilic peak in pregnancny
increases from 2nd month to a peak in the 2nd/3rd trimester
132
What happens to platelets in pregnancy
Gestational thrombocytopenia --> platelets fall after 20 weeks, most marked in late pregnancy
Occure due to folate defeciecny and pre eclampsia
133
What happens to coagulation in pregnancy
Pregnancy is pro-thrombotic state. Persists for 6-8 weeks after giving birth
134
Describe the changes that makes pregnancy prothrombotic
Increase in fibrinogen, factors V, VII, VII, X, XII, Minimal increase in IX, XIII increases initially then falls to 50% of pre pregnancy levels
Increase in procoagulant factors and platelet activation and thrombin generation markers
Decrease in natural anticoagulants and fibrinolysis
Increase in vWF (2fold more than increase in FVIII)
Small decrease in factor XI
