Anaemia & Thrombocytopenia Flashcards
What are some causes of anaemia, other than blood loss?
- haematinic deficiencies
- secondary to ‘chronic disease’
- haemolysis
- alcohol, drugs, toxins
- renal impairment - EPO
- primary haematological / marrow disease
- malignant
- haemoglobin disorders
- aplasia
- congenital
What is a hematinic?
a nutrient required for the formation of blood cells in the process of haematopoiesis
What is the MCV?
What does it measure and how is it calculated?
mean corpuscular volume
it measures the size and volume of a red blood cell
it can be used to determine the eitology of anaemia
it is calculated by multiplying the percentage haematocrit by ten and then dividing by the erythrocyte count
What are the 3 categories of anaemia depending on the MCV?
macrocytic:
- B12, folate, metabolic (e.g. thyroid / liver disease)
- marrow damage (alcohol, drugs, marrow disease)
- haemolysis (due to reticulocytosis)
normocytic:
- anaemia of chronic disease / inflammatory
microcytic:
- iron deficiency
- haemoglobin disorders
What is a very common cause of anaemia?
iron deficiency
the cause may matter more than the treatment
causes vary with age and sex
What is involved in iron balance?
How is it transported / stored?
Where is it absorbed?
it has no excretion and limited absorption
this is controlled at the level of the gut mucosa and most iron is recycled
it is absorbed in the duodenum and less so in the jejunum
it is transported by transferrin and stored in ferritin / haemosiderin
What is involved in the approach to treating iron deficiency anaemia?
- establish that there is an iron deficiency
- establish the cause of deficiency
- treat the low iron and the cause
What lab tests are used to establish iron deficiency?
- full blood count, indices and film
- ferritin
- % of hypochromic cells
- serum iron / TIBC
- marrow
What do the cells look like in anaemia caused by iron deficiency?
there are small pale red cells
there is low MCV and low MCH
What is MCV and MCH?
mean corpuscular volume:
- measures the size and volume of a red blood cell
- use in determining the etiology of anaemia
mean corpuscular haemoglobin:
- average amount of haemoglobin found in the red blood cells in the body
What are the main causes of iron-deficiency anaemia?
- blood loss from anywhere in the body
- increased demand e.g. pregnancy, growth
- reduced intake e.g. diet, malabsorption
What are the causes of iron deficiency anaemia in children?
- diet
- growth
- malabsorption
What are common causes of iron deficiency anaemia in young women?
- menstrual loss / problems
- pregnancy
- diet
What are the common causes of iron deficiency anaemia in older people?
- bleeding
- GI problems:
- ulcer / gastritis / aspirin
- malignancy
- diverticulitis
- GI surgery of various types
- others
What are the 3 different types of iron therapy?
- oral iron is often unreliable
- IM iron is painful
- IV iron is increasingly used
What is megaloblastic anaemia?
a characteristic cell morphology caused by impaired DNA synthesis
What do blood cells look like in megaloblastic anaemia?
large red blood cells with high MCV
What causes megaloblastic anaemia?
anaemia that results from inhibition of DNA synthesis during red blood cell production
when DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage
What are the causes of megaloblastic anaemia?
- B12 and/or folic acid deficiency
- alcohol
- drugs - cytotoxics, folate antagonists, N2O
- haematological malignancy
- congenital rarities
- transcobalamin deficiency
- orotic aciduria
How do vitamin B12 and folate cause anaemia?
- DNA consists of purine / pyramidine bases
- folate is required for their synthesis
- B12 is essential for cell folate generation
- low folate or B12 starves DNA of bases
What is involved in vitamin B12 absorption?
Where does it come from?
absorption involves:
- gastric parietal cells
- intrinsic factor
- receptors in terminal ileum
- there is lots of B12 in most diets compared to needs, but only from animal sources
- stores are sufficient for some years
In what conditions and circumstances is B12 deficiency seen?
- nutritional - vegans
- gastric problems
- pernicious anaemia (autoimmune)
- gastrectomy
- small bowel problems
- terminal ileum resection / Crohns
- stagnant loops / jejunal diverticulosis
- tropical sprue / fish tapeworm
Where is folic acid found?
How long do stores last for?
it is mainly in green vegetables, beans, peas, nuts and liver
the required intake needs a decent daily diet
it is absorbed in the upper small bowel and the body stores last for 4 months
What are the causes of folic acid deficiency?
- mainly dietary / malnutrition
- malabsorption / small bowel disease
- increased usage
- pregnancy
- haemolysis
- inflammatory disorders
- drugs / alcohol / ICU
What are features common to B12 or folate deficiency?
- megaloblastic anaemia
- pancytopenia in more severe cases
- mild jaundice
- glossitis / angular stomatitis
- anorexia / weight loss
- sterility
What is pancytopenia?
a deficiency of all three cellular components of the blood
(red cells, white cells and platelets)
What is glossitis?
inflammation of the tongue
it causes the tongue to swell in size, change in colour and develop a different appearance on the surface
What are the lab features of B12 and folate deficiency?
- blood count and film (sometimes marrow)
- bilirubin and LDH - ‘haemolysis’
- B12 and folate levels
- antibodies
- B12 absorption tests +/- IF
- GI investigations for Crohn’s, malabsorption, blind loop etc.
What is the classic cause of B12 deficiency?
pernicious anaemia
What is pernicious anaemia?
What causes it?
a deficiency in red blood cells caused by lack of vitamin B12 in the blood
vitamin B12 deficiency results from impaired uptake of vitamin B12 due to a lack of intrinsic factor produced by the stomach lining
What is pernicious anaemia associated with?
- antibodies to parietal cells / intrinsic factor
- autoimmune associations
- atrophic gastritis with achlorhydria
- incidence of stomach cancer
What is SACDC?
subacute combined degeneration of the cord
any cause of severe B12 deficiency
anaemia is not an absolute requirement
involves demyelination of dorsal + lateral columns and peripheral nerve damage
How does SACDC present?
- peripheral neuropathy / paraesthesiae
- numbness and distal weakness
- unsteady walking
- dementia
What is meant by paraesthesia?
an abnormal sensation, typically tingling or prickling (‘pins and needles’) caused mainly by pressure on or damage to peripheral nerves
What is shown here?
SACDC
subacute combined degeneration of the cord
What is the treatment for SACDC?
- B12 + folate until B12 deficiency is excluded
- B12 is given x5 and then given every 3 monthly for life
- folic acid is given 5mg daily to build stores
- there may be a need for potassium and iron initially
How is the response to treatment for SACDC monitored?
- retics by day 7
- blood count / MCV
- neuropathy
What is meant by ‘retics’?
reticulocyte count
this measures the levels of reticulocytes in the blood
it determines whether the bone marrow is producing enough red blood cells
What are reticulocytes and where do they originate from?
immature red blood cells
in the process of erythropoiesis, reticulocytes develop and mature in the bone marrow
they circulate for about a day in the bloodstream before they develop into mature red blood cells
What is haemolysis?
the rupture or destruction of red blood cells
this leads to a shortened red cell life
What are the 3 broad categories of causes of haemolysis?
- things wrong inside the red cell
- things wrong with the red cell membrane
- things wrong external to the red cell
What are the common causes of haemolysis in each of the 3 categories?
inside the cell:
- haemoglobinopathy (sickle cell)
- enzyme defects (G6PD)
membrane:
- hereditary spherocytosis / elliptocytosis
external to the cell:
- antibodies (warm / cold)
- drugs / toxins
- heart valves
- vascular / vasculitis / microangiopathy
What is the main enzyme defect that causes haemolysis?
glucose - 6 - phosphate dehydrogenase (G6PD) deficiency
this is a genetic disorder that most often affects males
G6PD protects red blood cells from damage and premature destruction
What is hereditary spherocytosis / elliptocytosis?
hereditary spherocytosis:
- mutations in genes relating to membrane proteins
- the erythrocytes change shape and become sphere-shaped
hereditary elliptocytosis:
- an abnormally large number of red blood cells are ellipitical rather than the typical biconcave disc shape
What is meant by “hot” and “cold” antibodies?
any red cell antibody that binds its target antigen best at levels below body temperature (37 C) is a “cold antibody”
“warm antibodies” react best at or near body temperature
What tests are used to determine the presence of haemolysis?
- anaemic
- high MCV, macrocytic
- high reticulocytes
- blood film showing fragments / spherocytes
- raised bilirubin & LDH
- low haptoglobins
- urinary haemosiderin
What is haptoglobin?
What is its function?
it binds to free haemoglobin released from erythrocytes, inhibiting its oxidative activity
it forms a complex that is rapidly removed from the circulation by the liver, and the iron is recycled
What does a low level of haptoglobin suggest?
a level below 45 mg / dl means that the red blood cells are being destroyed more quickly than they are being made
this is suggestive of haemolysis / anaemia
What does urinary haemosiderin measure?
urinary haemosiderin reflects haemoglobinuria and suggests severe or intravascular haemolysis
urinary haemoglobin is reabsorbed by renal tubular cells and is processed to haemosiderin
What tests are used to identify the cause of haemolysis?
- history + exam
- drug history incl alcohol, toxins, work
- positive DCT (evidence of antibody)
- blood film
- abnormal haemoglobins
- membrane studies
- enzyme studies
What is meant by a positive DCT?
What is an alternative name for this test?
Coombs’ test
it detects antibodies that act against the surface of red blood cells
the presence of these antibodies (postive test) indicated haemolytic anaemia
the blood does not contain enough red blood cells as they are destroyed prematurely
What is the treatment for autoimmune haemolytic anaemia?
it is managed with steroids and immunosuppression
transfusion in haemolysis can be difficult as it is hard to cross match
What is meant by anaemia of chronic disease?
a common general medical issue
can be malignant, inflammatory, infectious
present in multiple medical diseases including diabetes and autoimmune conditions
What features are typically seen in anaemia of chronic disease?
Why is there reduced red cell production?
typically there is a normal MCV
reduced red cell production is due to:
- abnormal iron metabolism
- poor erythropoietin response
- blunted marrow response
What is hepcidin?
What is its role?
it is a regulator of iron metabolism
it inhibits iron transport by binding to the iron export channel (ferroportin)
this is located on the basolateral surface of gut erythrocytes and the plasma membrane of reticuloendothelial cells (macrophages)
What are the effects of anaemia of chronic disease mediated by?
release of inflammatory cytokines:
- IL1, IL6, TNF-alpha
Hepcidin:
- regulator of iron absorption and release from macrophages
What are the features of anaemia of chronic disease?
How is ferritin, iron and transferrin usually affected?
- a suitable medical history and no other causes of anaemia
- anaemia is usually mild with normal MCV
- often raised inflammatory markers - ESR, CRP, PV
- normal / high ferritin and low serum iron
- normal % saturation of transferrin
What are the treatment options for anaemia of chronic disease?
- identify the cause if possible by a careful symptom assessment
- erythropoietin / iron IV
- potential transfusion
What are common causes of thrombocytopenia?
- drugs / alcohol / toxins
- ITP
- autoimmune diseases
- liver disease and / or hypersplenism
- pregnancy
- haematological / marrow diseases
- infections
- disseminated intravascular coagulation (DIC)
- range of congenital conditions
What is ITP?
What is it associated with?
immune thrombocytopenic purpura
a bleeding disorder in which the immune system destroys platelets
associated with lymphoma / CLL / HIV
What are the different types of immune thrombocytopenic purpura (ITP)?
a common immune disorder that occurs on its own or as part of:
- HIV
- lymphomas / CLL
- other autoimmune disease
it can be acute, chronic or relapsing
What is the presentaion of immune thrombocytopenic purpura like?
present with bruising or petechiae or bleeding
platelet count can be anything
What platelet counts should be looked for in immune thrombocytopenic purpura?
< 10 - urgent - query bleeding
<20 - concerning
< 30 - needs treatment
otherwise, platelet counts should be observed
What are the different therapies used in immune thrombocytopenic purpura?
- steroids are first line therapy
- IV immunoglobulin
- other immunosuppressives or splenectomy
- thrombo-mimetics
What are thrombomimetics?
What are the ones used in treatment for ITP?
they are newer drugs that have thrombopoeitin-like properties
eltrombopag and romiplostin are commonly used
What is the outcome like for most cases of ITP?
- usually rapid responses but can relapse after therapy
- rarely life-threatening
- commonly recurrent
What is thrombotic thrombocytopenia purpura?
a rare blood disorder characterised by clotting in small blood vessels (thromboses)
this results in a low platelet count
most cases are immune and it requires an urgent diagnosis
When should TTP be suspected?
What evidence should be looked for?
TTP should be expected if there is thrombocytopenia and:
- fever
- neurological symptoms
- haemolysis (retics / LDH)
seek evidence of microangiopathy from blood film fragments
What is involved in the urgent therapy used to treat thrombotic thrombocytopenia purpura (TTP)?
- plasma exchange with FFP/plasma
- steroids
- vincristine
- rituximab
- outcomes vary as there may be relapses so ADAMTS-13 is monitored
What is the function of ADAMTS13?
it is a von-Willebrand factor-cleaving protease
it cleaves vWF, a large protein involved in blood clotting
