Haem pathlology Flashcards
Anaemia
Haemoglobin level below normal for age and sex of the patient
Not a diagnosis but a feature of underlying pathology
Clinical features of anaemia
Pallor
Pale conjuctiva
Tachycardia
Increased pulse pressure
Symptoms of anaemia
Weakness Fatigue Lethargy Dizziness Headache
Severity of anaemia
Hb level
Rate of development
Age of the patient
Degree of physiological compensation
Anaemia causes
Decreased red cell production
- Bone marrow
- Reduced EPO
- Reduced DNA synthesis
- Reduced Hb synthesis
- Chronic disease
Increased red cell loss
- Blood loss
- Haemolysis
Testosterone in erythropoiesis
Drives erythropoiesis
Males have higher RBC count than females
Three types of anaemia
Microcytic (Low MCV, Low MCH)
Macrocytic (High MCV)
Normocytic
MCH
“Mean cell hemoglobin” (MCH), is the average mass of hemoglobin per red blood cell in a sample of blood
MCV
Mean corpuscular volume (MCV) is the average volume of red cells
Microcytic anaemia
Iron deficiency
Chronic disease anaemia
Thalassaemia
Macrocytic anaemia
Megaloblastic Liver disease Alcohol Pregnancy Hypothyroidism
Normocytic
Blood loss
Chronic disease
Renal failure
Haemolytic anaemias
Ferritin
Major storage protein of iron
Levels are proportional to the iron stores
Transferrin
Major transport protein of iron
Transferrin receptor
Cells absorb iron through internalisation of the transferrin bound to the transferrin receptor
**These levels increase in iron deficiency
Ferroportin
Transports iron across cell membranes to the plasma
What is the transporter on enterocytes
DMT1
Useful iron versus stored iron
Useful is Fe2+
Stored is Fe3+
Three main causes of iron deficiency
Decreased absorption
Increased use
Blood loss
How much iron is absorbed daily
1 mg
Blood film of iron deficiency anaemia
Hypochromic cells
Pencil cells
Microcytic
Low Hb
Low ferritin
Equals iron deficiency
*Careful in inflammation
Management
Oral iron therapy- safe, cheap, effective
Oral iron
Iron is best absorbed as ferrous salt
Ascorbic acid given to enhance absorption
150-200 mg/day
Keep going until ferritin stores are replenished
Adverse effects of oral iron
Nausea
Constipation
Diarrhoea
Abdominal pain
Where in the body is iron absorbed
Duodenum and proximal jejunum
Failure to respond to oral iron therapy
Malabsorption
Poor compliance
Ongoing blood loss
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)
Anaemia of inflammation
Blunted EPO response
Decreased red cell survival
Impaired absorption of iron due to hepcidin
Hepcidin
Released by liver in inflammation, causes internalisation and degradation of ferroportin
Management of anaemia of inflammation
Does not respond to oral iron
Combination of IV iron and EPO
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
Hb Barts/Hydrops fetalis
Cannot produce a globin
High affinity for oxygen, very poor oxygen delivery to tissues
HbH disease
Loss of three alpha genes, hypochromic microcytic anaemia
Unstable and precipitates causing damage to red cell membrane
Megaloblastocsis
Large oval shaped cells with immature nucleus
Increased erythroid activity
Occur in vitamin B12 or folate deficiency
Blood film in megaloblastic anaemia
Low reticulocyte count
Megaloblastic changes
Hypersegmented neutrophils
Severe cases- low platelets and white cells
Two reactions Vit B12 is needed for
1) Methylmalonyl mutase reaction (maintaining myelin in CNS)
2) Methionine synthetase reaction (DNA synthesis)
B12 deficiency reasons
Decreased dietary intake Decreased absorption Intestinal problems Increased excretion Increased demand
Clinical features in B12 deficiency
Pallor due to anaemia Glossitis GI disturbances Weight loss Psychiatric and neurological problems
Haemolysis
Increased red blood cell destruction and subsequent reduced red blood cell lifespan
Clinical features of haemolysis
Increased RBC destruction
Increased bilirubin
Increased lactate dehydrogenase
Dark urine
Causes of RBC destruction
Intrinsic
- Spherocytosis, elliptocytosis
- Hb- thalassaemia, sickle cell anaemia
- Enzyme- G6PD deficiency, PK deficiency
Extrinsic
- Trauma
- Infection (Malaria)
- Autoimmune haemolytic anaemia
Autoimmune haemolytic anaemia
Production of auto-antibodies against RBC causing haemolysis
What test is used to detect Autoimmune haemolytic anaemia
Coombs test (Positive direct antiglobulin test DAT)
Two subtypes of antibodies in Autoimmue haemolytic anaemia
IgG (Warm)
C3d (Cold)
Secondary causes of AIHA
Infection
Recent transfusion
Lymphoproliferative diseases
Medication or drug induced
Therapy for AIHA
Warm- steroids (prednisolone and dexamethasone)
Cold- Rituximab
Microangiopathic haemolytic anaemia
Red cell fragmentation
Causes:
Mechanical trauma
DIC
Drug induced
Primary vs Secondary haemostasis
Primary- vWF
Secondary- coagulation cascade
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
What causes bleeding
Abnormalities of vasculature
Defects of primary haemostasis
Defects of secondary haemostasis
Accelerated breakdown of clot
Platelet disorders
Quantitative
Qualitative
Both
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
Immune thrombocytopaenia purpura
Increased platelet destruction
Inhibition of megakaryocyte platelet production through IgG antibodies
Petechiae, epitaxis, bleeding gums
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
Abnormal platelet function
Congenital
- GP-Ib-IX-V- Bernard Soulier syndrome
- GPIIb/IIIa- Glanzmann thrombocytpaenia
Acquired
- Aspirin
- Clopidogrel
- Dipyridimole
Bleeding disorders causes
Congenital
- Haemophilia (A is FVIII, B is FIX)
- vWF disease
Acquired
- Liver disease
- Renal problems
Principles of mixing studies
Prolonged APTT or PT—–> Mix 50:50 patients plasma
- –> if normal (clotting factor deficiency)
- –> if not normal (clotting factor inhibitor)
vWF disease
Three types of vWD
1) Reduced vWF
2) Reduced function of vWF
3) Both leading to severe deficiency
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)
Vitamin K deficiency
Prolonged APTT and PT but normal fibrinogen
Because Vit K important for activation of 2,7,9,10
Why should all babies receive IM vit K at birth?
Vitamin K is ommitted at delivery
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
Causes of DIC
Sepsis
Pregnancy
Snake bite
Clinical presentation for DIC
Bleeding
Renal dysfunction
Shock
Hepatic dysfunction
Lab test findings for DIC
Prolonged APTT
Reduced fibrinogen
Low platelets
Raised D-dimers
Heparin causes what in lab tests
Prolonged APTT
Warfarin causes what in lab tests
Prolonged PT
Virchow’s triad
Abnormal blood flow
Hypercoagubility
Endothelial injury
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
Risk factors for VTE
Acquired
- Pregnancy
- Obesity
- Hospitalisation
- Oestrogen therapy
Inherited
- Antithrombin deficiency
- Protein C/S deficiency
Natural inhibitors of coagulation
Antithrombin (on X) Protein C (on V)
Protein S- activates protein C
Antithrombin
Major inhibitor of Factor Xa
Works slowly without heparin but fast with heparin
Protein C
Needs to be activated
Activated Protein C inactivates Factor V and VIIIa
Markedly enhanced effect due to Protein S
Protein S
Important in Protein C system
Acquired deficiency in pregnancy, OCP, liver disease, certain drugs, HIV infection
Factor V Leiden
Point mutation (Arg to Glu) where there is protein C resistance and protein C is unable to inactivate factor V
D-dimer
Plasmin breaks down cross-linked fibrin to D-dimers
Useful for VTE, DVT, DIC, infection, trauma
Why use D-Dimer?
Can exclude DVT/PT but not diagnose it
**High NPV but low PPV
Diagnosis of PE
Imaging
D-Dimer
V/Q scan
Warfarin
Blocks vitamin K epoxide reductase
Transfusion indications
Hb<70g/L
Raises it by 10g/L
Other blood products
Platelets
Fresh frozen plasma
Cryoprecipitate
Fresh frozen plasma
For clotting factors
Fibrinogen
vWF
Cryoprecipitate
Thawing FPP leaves a precipitate rich in fibrinogen.
Has 10x as fibrinogen
