Anaemia + Complications Flashcards
What is Anaemia?
- low level of haemoglobin
- result of underlying disease
What is
1. microcytic anaemia
2. normocytic anaemia
3. macrocytic anaemia
1.Low Hb with low mean cell volume
2. Low Hb with normal mean cell volume
3. Low Hb with high mean cell volume
Cause of Microcytic anaemia?
Mnemonic TAILS
T- Thalassaemia
A- Anaemia of chronic disease
I- Iron deficiency anaemia
L-Leas poisoning
S-Sideroblastic anaemia
Normocytic anaemia causes?
3As and 2Hs
A- Acute blood loss
A-Anaemia of chronic disease
A-Aplastic anaemia
H-Haemolytic anaemia
H-hypothyroidism
Types and causes of Macrocytic anaemia?
- Megaloblastic anaemia: B12 deficiency and Folate deficincy
- Normoblastic macrocytic anaemia: Alcohol, Reticulocytosis (usually from haemolytic anaemia or blood loss), Hypothyroidism, Liver disease,Drugs such as azathioprine
Symptoms of anaemia?
- Tiredness
- Shortness of breath
- Headaches
- Dizziness
- Palpitations
- Worsening of other conditions such as angina, heart failure or peripheral vascular disease
Symptoms of iron deficiency anaemia?
- Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency
- Hair loss can indicate iron deficiency anaemia
Signs of anaemia?
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised respiratory rate
Signs of anaemia?
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised respiratory rate
Specific signs of iron deficiency anaemia?
- Koilonychia- spoon shaped nails
- Angular chelitis
- Brittle hair and nails
Bloods for anaemia?
- Haemoglobin
- Mean Cell Volume (MCV)
- B12
- Folate
- Ferritin
- Blood film
What is Haemolytic anaemia?
- where there is destruction of red blood cells leading to anaemia
What causes haemolytic anaemia?
Think of broad classifications and then give examples of the conditions
Inherited
* Membrane: Hereditary spherocytosis/elliptocytosis
* metabolism: G6P deficiency
* Haemoglobinopathies: sickle cell, thalassaemia
Acquired
Immune (Coombs-positive):
* Autoimmune: warm/cold
* Alloimmune incl. transfusion reaction, haemolytic disease newborn
* Drug: methyldopa, penicillin
Non-immune (Coombs negative)
* Microangiopathic haemolytic anaemia: TTP/HUS, DIC, malignancy, pre-eclampsia
* Prosthetic heart valves
* paroxysmal nocturnal haemoglobinuria
* infections: malaria
* drug: dapsone
* Zieve syndrome
What is Zieve syndrome?
- rare clinical syndrome of Coombs-negative haemolysis, cholestatic jaundice, and transient hyperlipidaemia associated with heavy alcohol use, typically following a binge
- typically resolves with abstinence from alcohol
What happens to haemaglobin in intravascular haemolysis?
- Free haemoglobin is released which then binds to haptoglobin
- As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm’s test).
- Free haemoglobin is excreted in urine as haemoglobinuria, haemosideriuria
Cause of intravascular haemolysis?
- mismatched blood transfusion
- G6PD deficiency
- red cell fragmentation: heart valves, TTP, DIC, HUS
- paroxysmal nocturnal haemoglobinuria
- cold autoimmune haemolytic anaemia*
Extravascular haemolysis causes?
- haemoglobinopathies: sickle cell, thalassaemia
- hereditary spherocytosis
- haemolytic disease of newborn
- warm autoimmune haemolytic anaemia
Features of haemolytic anaemia?
- Anaemia- fatigue, breathlessness, palpitations
- Splenomegaly- as spleen becomes filled with destroyed RBC
- Jaundice- as bilirubin is released during destruction of RBCs
Investigations for haemolytic anaemia?
- Bedside: ECG- if pt has palpitations
- Bloods: FBC- normocytic anaemia
Blood film- schistocytes, reticulocytosis
If immune cause- positive coombs test
What is Hereditary Spherocytosis?
- Autosomal dominant condition
- Causes sphere shaped RBC- fragile and break down when passing through the spleen
- Most common hereditary haemolytic anaemia in people of northern European descent
Presentation of Hereditary spherocytosis?
- failure to thrive
- jaundice, gallstones
- splenomegaly
- aplastic crisis precipitated by parvovirus infection
- degree of haemolysis variable
- MCHC elevated
Diagnosis of Hereditary Spherocytosis?
- Diagnosis: Positive fhx, clinical features, typical lab investigations (spherocytes, increased reticulocytes, raised MCHC)- if this is all present, no additional tests are needed
- If diagnosis is ambiguous: EMA binding test and the cryohaemolysis
- atypical presentation: electrophoresis analysis of erythrocyte membranes
Managment of Hereditary spherocytosis?
- Folate replacement
- Splenectomy
- Acute haemolytic crisis:
treatment is generally supportive, transfusion if necessary
What is G6PD deficiency?
- Defect in red blood cell enzyme G6PD
- More common in Mediterranean and African patients
- X linked recessive
- Causes crises that are triggered by infections, medications (anti-malarials) or fava beans
How does G6PD deficiency present?
- Neonatal jaundice
- Gallstones
- Anaemia
- Splenomegaly
- Heinz bodies on blood film
*
How do you diagnose G6PD deficiency?
- G6PD enzyme assay
- measure the activity of the enzyme
What do you seen on blood film of G6PD deficiency?
- Heinz bodies
- Bite and blister cells may also be seen
When do you perform the enzyme assay for G6PD deficiency?
- around 3 months after an acute episode of haemolysis
- This is because during haemolysis the most severly affected RBC without G6PD will have hemolysed there fore will not be measured in the assay–> false negative results
- Therefore need to wait 3 months
What can precipitate a crisis in G6PD?
- Infection
- Fava beans
- Drugs: anti-malarials e.g. primaquine, ciprofloxacin, sulph groups (sulphonamides, sulphasalazine, sulfonylureas)
What is autoimmune haemolytic anaemia?
- Antibodies are created against the patients RBC
- This leads to the destruction of rbc
- 2 types- warm and cold
What are the investigation findings in autoimmune haemolytic anaemia?
General features of haemolytic anaemia:
* anaemia
* reticulocytosis
* low haptoglobin
* raised lactate dehydrogenase (LDH) and indirect bilirubin
* Blood film: spherocytes and reticulocytes
Specific features of autoimmune haemolytic anaemia:
Positive coombs test
What is Warm Autoimmune haemolytic anaemia (AIHA) ?
- The antibody (IgG usually) causes haemolysis best at body temp
- haemolysis tends to occur in extravascular sites e.g. spleen
Causes of warm AIHA?
- Idiopathic
- autoimmune disease e.g. SLE
- Neoplasia e.g. lymphoma or CLL
- Drugs e.g. methyldopa
Causes of warm AIHA?
- Idiopathic
- autoimmune disease e.g. SLE
- Neoplasia e.g. lymphoma or CLL
- Drugs e.g. methyldopa
Management of warm AIHA?
- Treatment of underlying disorder
- Steroids +/- rituximab are generally used first line
What is cold Autoimmune haemolytic anaemia?
- antibody usually IgM
- Causes haemolysis best at 4 degrees
- Mediated by complement
- more commonly intravascular
- Features may incl symptoms of raynauds and acrocyanosis
Pt responds less wel to steroids
What is cold Autoimmune haemolytic anaemia?
- antibody usually IgM
- Causes haemolysis best at 4 degrees
- Mediated by complement
- more commonly intravascular
- Features may incl symptoms of raynauds and acrocyanosis
Pt responds less wel to steroids
Causes of cold AIHA?
- Neoplasia e.g. lymphoma
- Infections e.g. mycoplasma, EBV
What is Paroxysmal Nocturnal Haemoglobinuria?
- RARE
- Specific genetic mutation in haematopoitic stem cells in bone marrow- occurs during pts lifetime
- Mutation results in loss of the proteins on the surface of red blood cells that inhibit the complement cascade
- Loss of protection against the complement system–> results in activation of complement cascade on the surface of RBC—> destruction of RBC
Presentation of Paroxysmal Nocturnal Haemoglobinuria?
- Red urine in the morning containing haemoglobin and haemosiderin
- Anaemia due to haemolysis
- Predisposed to thrombosis and smooth muscle dystonia (oesophageal spasm and erectile dysfunction)
Managment of Paroxysmal Nocturnal Haemoglobinuria?
- Eclizumab- monoclonal antibody that targets C5 causing suppression of the complement system
- Bone marrow transplantion can be curative
What can cause Microangiopathic Haemolytic Anaemia?
- Haemolytic Uraemic Syndrome (HUS)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenia Purpura (TTP)
- Systemic Lupus Erythematosus (SLE)
- Cancer
Management of Prosthetic valve haemolysis?
Monitoring
Oral iron
Blood transfusion if severe
Revision surgery may be required in severe cases
Diagnosis of Paroxysmal Nocturnal Haemoglobinuria?
- Flow cytometry of blood to detect low leverls of CD59 and CD55
What is anaemia of chronic disease?
- Anaemia due to chronic inflammation
- Functional problem: body has the iron but cannot use it
- Caused by malignancy, chronic infections, RA
Pathophysiology of Anaemia of Chronic disease?
- Chronic disease leads to chronic inflammation which causes IL-6 and IL-1 to be released
- high levels of IL-6 stimulated hepcidin release from liver–> hepcin inhibits iron absoprtion as it decreases the activity of ferroportin (iron channel on gut enterocytes and plasma membrane of reticuloendothelial cells- macrophages)
- This means that there is a reduction of plasma iron
- This causing inhibition of erythropoiesis in bone marrow
What are the blood results in Anaemia of Chronic disease?
- FBC- normochromic, normocytic anaemia (this progresses to microcytic, hypochromic type)
- Low TIBC
- High ferritin
- Low transferrin saturation
What is thrombocytopenia?
- Low platelet count
- Normal platelet count: 150-450 x 10^9/L
What conditons affects platelet production?
Resulting in thrombocytopenia ?
- Sepsis
- B12 or folic acid deficiency
- Liver failure causing reduced thrombopoietin production in the liver
- Leaukaemia
- Myelodysplastic syndrome
What causes platelet destruction?
Resulting in thrombocytopenia?
- Medications
- Alcohol
- Immune thrombocytopenia purpura
- Thrombotic thrombocytopenia purpura
- Heparin-induced thrombocytopenia
- Haemolytic uraemia syndrome
Presentation of thrombocytopenia?
- Mild: may be asymptomatic and found incidentally
- Below 50 x 10^9: easy or spontaneous bleeding, prolonged bleeding times, nosebleeds, bleeding gums, heavy periods, blood in urine or stool
- Below 10 x 106^9 : high risk for spontaneous bleeding. Spontaneous intracranial haemorrhage and GI bleeding are concerning
Ddx of abnormal/ prlonged bleeding time?
Thrombocytopenia
Haemophillia A and haemophillia B
Von Willebrand disease
DIC
What is Immune thrombocytopenia (ITP)?
- Immune mediated reduction in platelet count
- Antibodies against glycoprotein IIb/IIIa or Ib-V-IX complex
How does ITP differ in adults and children?
- Children have an acute thrombocytopenia that may follow infection or vaccination
- Adults tend to have a more chronic condition
Who gets ITP in adulthood?
- Older females
- associated with autoimmune haemolytic anaemia
How does ITP present in adults?
- may be detected incidentally following routine bloods
symptomatic patients may present with: - petechiae, purpura
- bleeding (e.g. epistaxis)
- catastrophic bleeding (e.g. intracranial) is NOT a common presentation
Investigations for ITP in adults?
- FBC- isolated thrombocytopenia
- Blood film
Management of ITP?
- First line: oral prednisolone
- IVIG (pooled normal human immunoglobulin) may also be used- raised platelet count quicker so may be used if active bleeding or urgent invasive procedure required
What is Evan’s syndrome?
- ITP in association with autoimmune haemolytic anaemia
What are the chains of haemoglobin called?
- 2 alpha chains
- 2 beta chains
What is alpha thalassaemia?
- caused by defects in alpha- globulin chains
- Gene coding for this is on chromosome 16
What is the severity of alpha thalassaemia dependent on?
- If 1 or 2 alpha globulin alleles are affected then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
- If are 3 alpha globulin alleles are affected results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
- If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hydrops fetalis, Bart’s hydrops)
*
Management of alpha thalassaemia?
- Monitoring the full blood count
- Monitoring for complications
- Blood transfusions
- Splenectomy may be performed
- Bone marrow transplant can be curative
What is beta thalassaemia?
- Defect in Beta globin chains
- gene coding for this on chromosome 11
What are the types of B thalassaemia and why is this the case?
Thalassaemia Minor
Thalassaemia Intermedia
Thalassaemia Major
- this is due to the gene defect consisting of abnormal copies that retain some function or deletion genes (no function in the beta-globin protein at all)
What is the Beta thalassaemia trait?
- SAME AS MINOR
- Autosomal recessive condition characterised by mild hypochromic, microcytic anaemia
- Usually asymptomatic
What are the features of beta thalassaemia minor/ trait?
- mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
- HbA2 raised (> 3.5%)
What is thalassaemia intermedia?
- 2 abnormal copies of the beta globin
- 2 defective copies or one defective gene and one deletion gene
Features of thalassaemia minor
- more significant microcytic anaemia
- pts require more monitoring and occasional blood transfusions
- if they require more transfusions may need iron chelation to prevent iron overload
What is beta thalassaemia major?
- Homozygous for the deletion genes
- No functioning beta-globin genes
- Most severe form
Features of beta- thalassaemia major?
- presents first year of life with failure to thrive and hepatosplenomegaly
- microcytic anaemia
- HbA2 & HbF raised
- HbA absent
Management of beta thalassaemia?
- Repeated transfusions–> leads to iron overload–> organ failure
- Iron chelation therapy is v imp
Most common inherited bleeding disorder?
- Von Willebrands Disease
What is Von Willebrands Disease?
- Autosomal dominant (classically)
- VW factor is a large glycoprotein which promotes platelet adhesion to damaged endothelium
- carrier molecule for factor VIII
- In this disease, the VWF does not work how it should
What are the types of VWD?
type 1: partial reduction in vWF (80% of patients)
type 2: abnormal form of vWF
type 3: total lack of vWF (autosomal recessive)
Presentation of VWD?
- Bleeding gums when brushing
- Epistaxis
- Menorrhagia
- Heavy bleeding in surgical operations
Investigations in VWD?
- Prolonged bleeding time
- APTT may be prolonged
- Factor VIII levels may be moderately reduced
- defective platelet aggregation with ristocetin
Management of VWD?
- Tranexamic acid for mild bleeding
- Desmopressin: raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- Factor VIII concentrate
Woman presents with very heavy periods with a background of VWD- what are management options for her?
- Tranexamic acid
- Norethisterone
- COCP
- Mirena coil
What is Haemophilia?
- X-linked recessive disorder of coagulation
- up to 30% of the patients have no fhx of the condition
Difference between Haemophilia A and B?
- A- due to deficiency of factor VIII
- B- deficiency of factor IX
Features of haemophilia?
- Haemoarthroses
- Haematomas
- Prolonged bleeding after surgery or trauma
Abnormal bleeding can occur in other areas: - Gums
- Gastrointestinal tract
- Urinary tract causing haematuria
- Retroperitoneal space
- Intracranial
- Following procedures
Blood tests in Haemophilia?
- APTT- prolonged
- Bleeding time, thrombin time and prothrombin time normal
Managment of Haemophilia?
- The affected clotting factors (VIII or IX) can be replaced by IV infusions
- Prophulactically or in response to bleeding
Complications of haemophilia treatment?
- Antibodies to the clotting factor–> treatment becomes ineffective
Which drugs can cause haemolytic anaemia?
- Methyldopa
- Penicillin
*
Causes of neutropenia?
Severe sepsis
Viral infection
Drugs
Marrow failure (due to malignancy or infiltration
Hypersplenism (less common)
Felty’s syndrome (less common)
SLE (less common)
What is feltys syndrome?
Triad of:
* splenomegaly
* Rheumatoid arthritis
* neutropenia
Causes of lymphocytosis?
Acute viral infection (especially EBV and CMV)
Chronic atypical infection (tuberculosis, brucella, toxoplasmosis)
Lymphoproliferative disorders (chronic lymphocytic leukaemia and lymphoma).
What haematological side effects can steroids have?
- Raised white cell count?
Causes of Leukocytosis?
- ALL specifically
- Infection
- Malignancy
