Haem pathlology Flashcards
(84 cards)
1
Q
Anaemia
A
Haemoglobin level below normal for age and sex of the patient
Not a diagnosis but a feature of underlying pathology
2
Q
Clinical features of anaemia
A
Pallor
Pale conjuctiva
Tachycardia
Increased pulse pressure
3
Q
Symptoms of anaemia
A
Weakness Fatigue Lethargy Dizziness Headache
4
Q
Severity of anaemia
A
Hb level
Rate of development
Age of the patient
Degree of physiological compensation
5
Q
Anaemia causes
A
Decreased red cell production
- Bone marrow
- Reduced EPO
- Reduced DNA synthesis
- Reduced Hb synthesis
- Chronic disease
Increased red cell loss
- Blood loss
- Haemolysis
6
Q
Testosterone in erythropoiesis
A
Drives erythropoiesis
Males have higher RBC count than females
7
Q
Three types of anaemia
A
Microcytic (Low MCV, Low MCH)
Macrocytic (High MCV)
Normocytic
8
Q
MCH
A
“Mean cell hemoglobin” (MCH), is the average mass of hemoglobin per red blood cell in a sample of blood
9
Q
MCV
A
Mean corpuscular volume (MCV) is the average volume of red cells
10
Q
Microcytic anaemia
A
Iron deficiency
Chronic disease anaemia
Thalassaemia
11
Q
Macrocytic anaemia
A
Megaloblastic Liver disease Alcohol Pregnancy Hypothyroidism
12
Q
Normocytic
A
Blood loss
Chronic disease
Renal failure
Haemolytic anaemias
13
Q
Ferritin
A
Major storage protein of iron
Levels are proportional to the iron stores
14
Q
Transferrin
A
Major transport protein of iron
15
Q
Transferrin receptor
A
Cells absorb iron through internalisation of the transferrin bound to the transferrin receptor
**These levels increase in iron deficiency
16
Q
Ferroportin
A
Transports iron across cell membranes to the plasma
17
Q
What is the transporter on enterocytes
A
DMT1
18
Q
Useful iron versus stored iron
A
Useful is Fe2+
Stored is Fe3+
19
Q
Three main causes of iron deficiency
A
Decreased absorption
Increased use
Blood loss
20
Q
How much iron is absorbed daily
A
1 mg
21
Q
Blood film of iron deficiency anaemia
A
Hypochromic cells
Pencil cells
Microcytic
Low Hb
22
Q
Low ferritin
A
Equals iron deficiency
*Careful in inflammation
23
Q
Management
A
Oral iron therapy- safe, cheap, effective
24
Q
Oral iron
A
Iron is best absorbed as ferrous salt
Ascorbic acid given to enhance absorption
150-200 mg/day
Keep going until ferritin stores are replenished
25
Adverse effects of oral iron
Nausea
Constipation
Diarrhoea
Abdominal pain
26
Where in the body is iron absorbed
Duodenum and proximal jejunum
27
Failure to respond to oral iron therapy
Malabsorption
Poor compliance
Ongoing blood loss
28
Parenteral iron therapy
For patients unable to tolerate oral iron or non-compliant, high rate of loss
Products- Iron polymaltose (Ferrosig) and Iron carboxymaltose (Ferrinject)
29
Anaemia of inflammation
Blunted EPO response
Decreased red cell survival
Impaired absorption of iron due to hepcidin
30
Hepcidin
Released by liver in inflammation, causes internalisation and degradation of ferroportin
31
Management of anaemia of inflammation
Does not respond to oral iron
| Combination of IV iron and EPO
32
B thalassaemia major
Cannot produce any B globin
a globin precipitates and damages developing erythroid cells and breakdown of cells occurs in the bone marrow
Ineffective erythropoiesis and shortened red cell survival leading to severe transfusion dependent anaemia
33
Hb Barts/Hydrops fetalis
Cannot produce a globin
| High affinity for oxygen, very poor oxygen delivery to tissues
34
HbH disease
Loss of three alpha genes, hypochromic microcytic anaemia
| Unstable and precipitates causing damage to red cell membrane
35
Megaloblastocsis
Large oval shaped cells with immature nucleus
Increased erythroid activity
Occur in vitamin B12 or folate deficiency
36
Blood film in megaloblastic anaemia
Low reticulocyte count
Megaloblastic changes
Hypersegmented neutrophils
Severe cases- low platelets and white cells
37
Two reactions Vit B12 is needed for
1) Methylmalonyl mutase reaction (maintaining myelin in CNS)
| 2) Methionine synthetase reaction (DNA synthesis)
38
B12 deficiency reasons
```
Decreased dietary intake
Decreased absorption
Intestinal problems
Increased excretion
Increased demand
```
39
Clinical features in B12 deficiency
```
Pallor due to anaemia
Glossitis
GI disturbances
Weight loss
Psychiatric and neurological problems
```
40
Haemolysis
Increased red blood cell destruction and subsequent reduced red blood cell lifespan
41
Clinical features of haemolysis
Increased RBC destruction
Increased bilirubin
Increased lactate dehydrogenase
Dark urine
42
Causes of RBC destruction
Intrinsic
- Spherocytosis, elliptocytosis
- Hb- thalassaemia, sickle cell anaemia
- Enzyme- G6PD deficiency, PK deficiency
Extrinsic
- Trauma
- Infection (Malaria)
- Autoimmune haemolytic anaemia
43
Autoimmune haemolytic anaemia
Production of auto-antibodies against RBC causing haemolysis
44
What test is used to detect Autoimmune haemolytic anaemia
Coombs test (Positive direct antiglobulin test DAT)
45
Two subtypes of antibodies in Autoimmue haemolytic anaemia
IgG (Warm)
| C3d (Cold)
46
Secondary causes of AIHA
Infection
Recent transfusion
Lymphoproliferative diseases
Medication or drug induced
47
Therapy for AIHA
Warm- steroids (prednisolone and dexamethasone)
| Cold- Rituximab
48
Microangiopathic haemolytic anaemia
Red cell fragmentation
Causes:
Mechanical trauma
DIC
Drug induced
49
Primary vs Secondary haemostasis
Primary- vWF
| Secondary- coagulation cascade
50
Endothelial injury
Platelets go to the site and bind to subendothelial collagen to initiate primary closure of the vessel wall defect
TF combines with factor VII. FVIIa-TF activate other clotthing proteins to produce thrombin which converts fibrinogen to fibrin to stabilise the clot
51
What causes bleeding
Abnormalities of vasculature
Defects of primary haemostasis
Defects of secondary haemostasis
Accelerated breakdown of clot
52
Platelet disorders
Quantitative
Qualitative
Both
53
Causes of thrombocyopaenia
Congenital disorders
Acquired
- Impaired bone marrow production (leukaemia, myelodysplasia)
- Increased platelet destruction (Sepsis, DIC, ITP, autoimmune conditions, Pre-eclampsia)
- Hypersplenism
- Drug induced
54
Immune thrombocytopaenia purpura
Increased platelet destruction
Inhibition of megakaryocyte platelet production through IgG antibodies
Petechiae, epitaxis, bleeding gums
55
Platelet function in haemostasis
Platelets bind to surface receptors (GP1b through vWF and GPVI to collagen)
They then change shape
Express GPIIb/IIIa
Produce ADP/TxA2 to recruit more platelets to produce platelet plug
56
Abnormal platelet function
Congenital
- GP-Ib-IX-V- Bernard Soulier syndrome
- GPIIb/IIIa- Glanzmann thrombocytpaenia
Acquired
- Aspirin
- Clopidogrel
- Dipyridimole
57
Bleeding disorders causes
Congenital
- Haemophilia (A is FVIII, B is FIX)
- vWF disease
Acquired
- Liver disease
- Renal problems
58
Principles of mixing studies
Prolonged APTT or PT-----> Mix 50:50 patients plasma
- --> if normal (clotting factor deficiency)
- --> if not normal (clotting factor inhibitor)
59
vWF disease
Three types of vWD
1) Reduced vWF
2) Reduced function of vWF
3) Both leading to severe deficiency
60
Management of vWD
1) Desmopressin (release of vWF from stored granules)
2) Tranexamic acid tablets (stabilise fibrin clot)
3) Biostate (product with FVIII and vWF)
61
Vitamin K deficiency
Prolonged APTT and PT but normal fibrinogen
| Because Vit K important for activation of 2,7,9,10
62
Why should all babies receive IM vit K at birth?
Vitamin K is ommitted at delivery
63
Disseminated intravascular coagulation (DIC)
Systemic process where blood is exposed to pro-coagulant factor
Leading to widespread coagulation, massive thrombin generation, depletion of clotting factors
64
Causes of DIC
Sepsis
Pregnancy
Snake bite
65
Clinical presentation for DIC
Bleeding
Renal dysfunction
Shock
Hepatic dysfunction
66
Lab test findings for DIC
Prolonged APTT
Reduced fibrinogen
Low platelets
Raised D-dimers
67
Heparin causes what in lab tests
Prolonged APTT
68
Warfarin causes what in lab tests
Prolonged PT
69
Virchow's triad
Abnormal blood flow
Hypercoagubility
Endothelial injury
70
Venous thromboembolism
Venous thromboembolism (VTE) is the formation of blood clots in the vein. When a clot forms in a deep vein, usually in the leg, it is called a deep vein thrombosis or DVT
71
Risk factors for VTE
Acquired
- Pregnancy
- Obesity
- Hospitalisation
- Oestrogen therapy
Inherited
- Antithrombin deficiency
- Protein C/S deficiency
72
Natural inhibitors of coagulation
```
Antithrombin (on X)
Protein C (on V)
```
Protein S- activates protein C
73
Antithrombin
Major inhibitor of Factor Xa
| Works slowly without heparin but fast with heparin
74
Protein C
Needs to be activated
Activated Protein C inactivates Factor V and VIIIa
Markedly enhanced effect due to Protein S
75
Protein S
Important in Protein C system
| Acquired deficiency in pregnancy, OCP, liver disease, certain drugs, HIV infection
76
Factor V Leiden
Point mutation (Arg to Glu) where there is protein C resistance and protein C is unable to inactivate factor V
77
D-dimer
Plasmin breaks down cross-linked fibrin to D-dimers
| Useful for VTE, DVT, DIC, infection, trauma
78
Why use D-Dimer?
Can exclude DVT/PT but not diagnose it
**High NPV but low PPV
79
Diagnosis of PE
Imaging
D-Dimer
V/Q scan
80
Warfarin
Blocks vitamin K epoxide reductase
81
Transfusion indications
Hb<70g/L
Raises it by 10g/L
82
Other blood products
Platelets
Fresh frozen plasma
Cryoprecipitate
83
Fresh frozen plasma
For clotting factors
Fibrinogen
vWF
84
Cryoprecipitate
Thawing FPP leaves a precipitate rich in fibrinogen.
| Has 10x as fibrinogen
