Common causes of anaemia and thrombocytopenia Flashcards
What are the 6 causes of anaemia other than blood loss?
1) Haematinic deficiencies (includes, iron, B12 and folate (B9))
2) Secondary to chronic disease
3) Haemolysis
4) Alcohol, drugs and toxins causing anaemia
5) Renal impairment (EPO)
6) Primary haematological/ marrow disease
What are the 3 types of anaemia as defined by the MCV?
1) Macrocytic
2) Normocytic
3) Microcytic
What are the 3 causes of macrocytic anaemia?
1) B12, folate, metabolic (eg. thyroid/liver disease)
2) Marrow damage (alcohol, drugs, marrow disease)
3) Haemolysis (due to reticulocytosis - reticulocytes are immature RBCs which are physically larger and are churned out when the rate of haemolysis is high as bone marrow cant keep up)
What is the cause of normocytic anaemia?
Anaemia of chronic disease/ inflammatory (NB anaemia of chronic disease is sometimes microcytic)
What are the 2 causes of microcytic anaemia?
1) Iron deficiency
2) Hb disorders
(NB sometimes chronic disease)
How is iron balance maintained, where is it absorbed?
- There is no excretion of iron so there is limited absorption, most iron is thus recycled
- This is controlled at the level of the gut mucosa, iron is absorbed in the duodenum (less in jejunum)
How is iron transported and stored?
Iron is transported by transferrin and stored in ferritin/haemosiderin
What are the 3 lab tests to establish low iron?
1) FBC, indices and film (expect to see microcytic anaemia)
2) Ferritin - key test for iron deficiency
3) %hypochromic cells - elevated %hypochromic cells indicates iron deficiency
Are serum iron and total iron binding capacity (TIBC) test for iron deficiency?
No - they are useful for problems with iron metabolism but are not tests for iron deficiency
How would you expect red cells to appear on blood film in iron deficiency?
Small, pale red cells (low MCV and low MCH (Hb conc))
What are the 3 main causes of iron deficiency?
1) Blood loss from anywhere - gut/PV/PU/resp tract
2) Increased demand - pregnancy/growth
3) Reduced intake - diet/malabsorption
What are the 3 main causes of iron deficiency in children?
1) Diet
2) Growth
3) Malabsorption
What are the 3 main causes of iron deficiency in young women?
1) Menstrual loss/problems
2) Pregnancy - don’t underestimate the potential for long term deficiency after this
3) Diet
What are the 2 main causes of iron deficiency in older people?
1) Bleeding
2) GI problems: ulcer/gastritis/aspirin, malignancy, diverticulitis, GI surgery, others
What are the 3 possible iron therapies, which is better?
1) Oral iron - often unreliable
2) IM iron - painful and out of date
3) IV iron - increasingly used
What is megaloblastic anaemia, what is it typically caused by?
A characteristic cell morphology caused by impaired DNA synthesis - have a high MCV - big red cells
What are the 5 causes of megaloblastic anaemia?
1) B12 and/or folate deficiency
2) Alcohol
3) Drugs - cytotoxics, folate antagonists, N2O
4) Haematological malignancy
5) Congenital rarities
Which 2 congenital rarities can cause megaloblastic anaemia?
1) Transcobalamin deficiency
2) Orotic aciduria
Why do B12 and folate deficiencies cause anaemia?
- DNA consists of purine/ pyrimidine bases
- Folates are required for their synthesis
- B12 is essential for cell folate generation
- So low folate or B12 starves DNA of bases
How is vit B12 absorbed?
- Gastric parietal cells produce intrinsic factor
- Intrinsic factor combines with B12 and this complex is absorbed in the terminal ileum
Can you get B12 deficiency for diet?
No - there is loads in the diet compared to needs, we need very little and in health it is absorbed very well (it only comes from animal sources but the microbes on food offer sufficient source)
What are the 2 main reasons for B12 deficiency?
1) Gastric problems - pernicious anaemia (autoimmune) and gastrectomy
2) Small bowel problems - terminal ileum resection/ crohns, stagnant loops/ jejunal diverticulosis, tropical sprue/ fish tapeworm
(Possibly due to diet in vegans)
In what kind of foods is folic acid (B9) found?
Mainly in green veg, beans, peas, nuts and liver
Where is folic acid absorbed?
Upper small bowel
How much folic acid is required from the diet?
Requires a decent daily diet
What is the size of the bodies folate stores?
4 months body stored
What are the 4 causes of folic acid deficiency?
1) Mainly dietary/ malnutrition
2) Malabsorption/ small bowel disease
3) Increased usage - pregnancy, haemolysis, inflammatory disorders
4) Drugs/ alcohol/ ITU
Give the 6 features common to both B12 and folate deficiency?
1) Megaloblastic anaemia
2) Can have pancytopenia if more severe
3) Mild jaundice
4) Glossitis/ angular stomatitis
5) Anorexia/ weight loss
6) Sterility
Give the 6 lab tests to investigate folate and B12 deficiency?
1) Blood count and film - marrow sometimes
2) Bilirubin and LDH - haemolysis - megaloblastic cells break down quicker so see some features of haemolysis
3) B12 and folate levels assay
4) Antibodies (to chief cells ?pernicious anaemia)
5) B12 absorption tests +/- IF
6) GI investigations - Crohn’s, malabsorption, blind loop etc.
What is the classic cause of B12 deficiency?
Pernicious anaemia
What is pernicious anaemia?
Have Abs to parietal cells/ intrinsic factor, associated with autoimmune diseases. Get gastritis with achlorhydia and is associated with incidence of Ca stomach
What neurological condition can any cause of severe B12 deficiency with or without anaemia cause?
Subacute combine degeneration of the cord SACDC
What is SACDC, how does it present? 4
Get demyelination of dorsal and lateral columns Also get peripheral nerve damage Presents as: - Peripheral neuropathy/ paraesthesia - Numbness and distal weakness - Unsteady walking - Dementia
Why should a patient not be given folic acid in isolation until you have excluded the diagnosis of B12 deficiency?
Because if you give folic acid in isolation and it is actually B12 deficiency then you can exacerbate the neurological problems
What is the treatment for B12 and folate deficiency? 4
1) B12 + Folate until B12 deficiency excluded
2) B12 x 5 then 3 monthly for life PA
3) Folic acid daily 5mg to build stores
4) ?need for potassium and iron daily
What 3 investigations/ findings are used to monitor the efficacy of treatment for B12 and folate?
1) Retics (reticulocyte count) by day 7
2) Blood count/ MCV
3) Neuropathy - need many months of treatment for this to disappear
What is important to think when treating iron, B12 and folate deficiency?
Don’t just replace the deficiency investigate and treat the cause
What are the 3 basic causes of haemolysis (shortened red cell life)?
1) Things are wrong inside the cell
2) Things are wrong with the red cell membrane
3) Things are wrong external to the red cell
Give the 2 common causes of things inside the red cell causing haemolysis?
1) Haemoglobinopathy (sickle cell)
2) Enzyme defects (G6PD)
Give the 2 common cause of haemolysis associated with faulty membranes?
1) Hereditary spherocytosis
2) Hereditary elliptocytosis
Give the 4 causes of haemolysis associated with things external to the RBC?
1) Antibodies
2) Drugs, toxins
3) Heart valves
4) Vascular/ vasculitis/ microangiopathy
Give the 7 investigations to show the presence of haemolysis?
1) Anaemic (or not - may be compensated)
2) High MCV, macrocytic (because of reticulocyte formation - larger than mature RBCs)
3) High reticulocytes
4) Blood film (fragments seen/ spherocytes)
5) Raised bilirubin, LDH
6) Low haptoglobins (protein produced in the liver which binds with Hb)
7) Urinary haemosiderin (stores iron)
What would a positive direct coombes test in haemolysis suggest?
Evidence of an Ab contributing to the cause
Each cause of haemolysis has its own specific treatment what is the treatment for autoimmune haemolytic anaemia (AIHA)?
Steroids/ immunosuppression
Can transfusion be used to treat haemolysis?
Can be difficult in AIHA as its hard to cross match
In anaemia of chronic disease, what is the MCV?
Typically normal
What is the cause of reduced red cell production in chronic disease? 3
1) Abnormal iron metabolism
2) Poor erythropoietin response
3) Blunted marrow response
What is hepcidin?
A regulator of iron absorption and release from macrophages
What 2 substances are the effects of chronic disease on red blood cell production mediated by?
1) Inflammatory cytokines - IL1, IL6, TNF-alpha
2) Hepcidin - produced in the liver, regulator of iron absorption and release from macrophages
What are the 6 clinical features of anaemia of chronic disease?
1) No other cause of anaemia evident
2) A suitable medical history
3) Often raised inflammatory markers - ESR, CRP, PV
4) Normal/ high ferritin + low serum iron
5) Normal % saturation transferrin
6) Usually mild anaemia with a normal MCV
What is the treatment for anaemia of chronic disease? 3
1) Treat the cause if possible
2) EPO/ iron
3) Possibly a transfusion - severe cases as a last resort
Give the 9 common causes of thrombocytopenia?
1) Drugs, alcohol, toxins
2) Immune thrombocytopenic purpura, ITP (sometimes associated with lymphoma/ CLL/ HIV)
3) Other autoimmune diseases
4) Liver disease and/or hypersplenism
5) Pregnancy (both physiological and in a range of complications)
6) Haematological/ marrow diseases
7) Infections
8) DIC
9) Range of congenital conditions
What is immune thrombocytopenic purpura (ITP)?
Common conditions, an immune disorder, can be acute, chronic or relapsing
ITP can occur in isolation or as part of what 3 other disorders?
1) Other autoimmune diseases
2) Lymphomas/ CLL
3) HIV
What is the presentation of ITP? 3
1) Bruising or petechiae or bleeding
2) Platelet count can be anything
3) May be a prodrome or associated disease
How can you test for ITP?
There is no definitive test - diagnosis once you have excluded other causes
What are the 4 possible treatments for ITP?
1) Steroid remains first line
2) IV immunoglobulin
3) Other immunosuppressives or splenectomy are common next options
4) Newer thrombo-mimetics now have a place and are becoming more widely used - romiplostin, eltrombopag
How do newer thrombo-mimetics used to treat ITP work?
Have thrombopoeitin-like properties
This stimulates the production of platelets
What are the common outcomes of treatment of ITP?
1) Usually rapid response
2) Can relapse after therapy
3) Rarely life-threatening but commonly recurrent
4) Some difficult refractor cases
Why is it importnat to recognise thrombotic thrombocytopenia purpura (TTP)?
It is a rare but urgent diagnosis
What is the cause of thrombotic thrombocytopenic purpura?
Most are immune - caused by an Ab against ADAMTS-13 which normally keeps all this stuff ok, to do with abnormal epithelium
Get microthrombi followed by a period of DIC, neurology is caused by all the clots forming everywhere
But this is a very treatable condition
You should suspect thrombotic thrombocytopenic purpura if a patient has thrombocytopenia along with what 3 symptoms?
1) Fever
2) Neurological symptoms
3) Haemolysis (retics/ LDH)
What test should you do in suspected TTP?
Seek evidence of microangiopathy (small vessel disease) using a blood film as its to do with abnormal epithelium
What 4 things does the urgent therapy for TTP include?
1) Plasma exchange with FFP/ Plasma
2) Steroids
3) Vincristine
4) Rituximab
What is ADAMTS13?
Also known as Von Willebrand factor which cleaves vWF
