Haematology Flashcards
1
Q
Difference between whole blood, blood plasma and serum ?
A
Whole blood = everything i.e. includes RBCs, WBCs and platelets
Blood plasma = Fluid portion of the blood i.e. excludes RBCs, WBCs and platelets.
Serum = what’s left after the clotting factors are removed from blood plasma.
2
Q
What does serum contain ?
A
-Glucose
-Electrolytes e.g. sodium, potassium
-Proteins such as immunoglobulins and hormones
3
Q
Blood cells develop in the bone marrow. Bone marrow is mostly found in the pelvis, vertebrae, ribs and sternum. Pluripotent haematopoietic stem cells are undifferentiated cells that have the potential to transform into a variety of blood cells. They initially become what ?
A
-Myeloid stem cells (develop in the bone marrow)
-Lymphoid stem cells (develop in the lymphatic tissue)
-Dendritic cells (via various intermediate stages)
4
Q
How are RBCs formed + what is their lifespan ?
A
They develop from reticulocytes (immature RBCs) that come from the myeloid stem cells. Their lifespan is approximately 120 days.
5
Q
How are platelets formed + what is their lifespan
A
They are made by megakaryocytes that come from myeloid stem cells. Thier lifespan is 10 days.
6
Q
Myeloid stem cells become myeloblasts that produce ?
A
-Monocytes then macrophages (in the tissues)
-Neutrophils
-Basophils
-Eosinophils
-Mast cells
7
Q
Lymphocytes come from the lymphoid stem cells and become B cells or T cells. Where do B cells mature and what do they differentiate into + where do T cells mature and what do they differentiate into ?
A
B lymphocytes mature in the bone marrow and differentiate into:
-Plasma cells
-Memory cells
T lymphocytes in the thymus gland and differentiate into:
-CD4 cells (T helper cells)
-CD8 cells (cytotoxic T cells)
-Natural killer cells
8
Q
What do each of these blood film findings mean and where can they be seen :
-Anisocytosis
-Target cells
-Heinz bodies
-Reticulocytes
-Schistocytes
-Sideroblasts
-Smudge cells
-Spherocytes
A
-Anisocytosis: Refers to a variation in the size of RBCs. These can be seen in myelodysplasic syndrome as well as some forms of anaemia.
-Target cells: have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target. These can be seen in iron deficiency anaemia and post-splenectomy.
-Heinz bodies: Are individual blobs seen inside RBCs cause by denatured globin. They can be seen in G6PD and alpha-thalassaemia
-Reticulocytes: Are immature RBCs that are slightly larger than standard erythrocytes and still have RNA material in them. The RNA has a reticular (“mesh like”) appearance inside the cell. It is normal for about 1% of RBCs to be reticulocytes. This % goes up where there is rapid turnover of RBCs such as haemolytic anaemia. They demonstrate that the bone marrow is active in replacing lost cells.
-Schistocytes: Are fragments of RBCs. They indicate the RBCs are being physically damaged by trauma and during their journey through the blood vessels. They may indicate networks of clots in small blood vessels caused by HUS, DIC or thrombotic thrombocytopenic purpura. They can also be present in replacement metallic heart valves and haemolytic anemia.
-Sideroblasts: Are immature RBCs that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate myelodysplasic sydndrome.
-Smudge cells: Are ruptured WBCs that occur during the process of preparing the blood film due to aged or fragile WBCs. They can indicate chronic lymphocytic leukaemia.
-Spherocytes: Are spherical RBCs without the normal bi-concave disk shape. They can indicate autoimmune haemolytic anaemia or hereditary spherocytosis
9
Q
What is anaemia ?
A
A low level of haemoglobin in the blood.
Note: This is the result of an underlying disease and is not a disease itself.
10
Q
You can diagnose a pt with anaemia when they have a low haemoglobin. When you find an anaemic pt you should also check what ?
A
Mean cell volume (MCV)
11
Q
Anaemia is subdivided into three main categories, what are they ?
A
Microcytic anaemia (low MCV)
Normocytic anaemia (normal MCV)
Macrocytic anaemia (high MCV)
12
Q
Causes of microcytic anaemia ?
A
TAILS
T - Thalassaemia
A - Anaemia of chronic disease
I - Iron defiency anaemia
L - Lead poisoning
S - Sideroblastic anaemia
13
Q
Causes of normocytic anaemia ?
A
3 As and 2 Hs
A - Acute blood loss
A - Anaemia of chronic disease
A - Aplastic anaemia
H - Haemolytic anaemia
H - Hypothyroidism
14
Q
Macrocytic anaemia can but into two different categories, what are they ?
A
Megaloblastic or normoblastic
15
Q
What is megaloblastic anaemia the result of ?
A
Impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a large, abnormal cell.
Note: This is caused by a vitamin deficiency.
16
Q
What is megaloblastic anaemia caused by ?
A
-B12 deficiency
-Folate deficiency
17
Q
Normoblastic macrocytic anaemia is caused by ?
A
-Alcohol
-Reticulocytosis (usually from haemolytic anaemia or blood loss)
-Hypothyroidism
-Liver disease
-Drugs such as azathioprine
18
Q
Name 6 generic symptoms of anaemia ?
A
-Tiredness
-SOB
-Headaches
-Dizziness
-Palpitations
-Worsening of other conditions such as angina, heart failure or peripheral vascular disease
19
Q
Name 2 symptoms specific to iron deficiency anaemia ?
A
- Pica - describes dietary cravings for abnormal things such as dirt
- Hair loss
20
Q
Name 4 generic signs of anaemia ?
A
-Pale skin
-Conjunctival pallor
-Tachycardia
-Raised resp rate
21
Q
Name some signs of specific causes of anaemia ?
A
-Koilonychia - can indicate iron deficiency
-Angular chelitis - can indicate iron deficiency
-Atrophic glossitis - is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency
-Brittle hair and nails can indicate iron deficiency
-Jaundice occurs in haemolytic anaemia
-Bone deformities occur in thalassaemia
-Oedema, HTN and excoriations on the skin can indciate CKD.
22
Q
Investigations for anaemia (both initial and further) ?
A
Initial:
-Hb
-MCV
-B12
-Folate
-Ferritin
-Blood film
Further investigations:
-Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for a GI cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected GI cancer
-Bone marrow biopsy may be required if the cause is unclear.
23
Q
Scenarios when iron stores can be used up and the pt can become iron deficient ?
A
-Insufficient dietary iron
-Iron requirements increase e.g. pregnancy
-Iron is being lost e.g. bleeding from a colon cancer
-Inadequate iron absorption
24
Q
Where is iron mainly absorbed ?
A
In the duodenum and jejunum.
25
What does iron require to keep it in a soluble form + what form is this + what is the insoluble form/ when does this occur?
Acid from the stomach.
Fe2+ (ferrous) form.
When the acid level drops it changes to the insoluble Fe3+ (ferric) form.
26
Which medications can interfere with iron absorption ?
Medications that reduce stomach acid e.g. PPIs as they reduce the amount of stomach acid being produced
27
What conditions can cause inadequate iron absorption ?
Conditions that result in inflammation of the duodenum or jejunum e.g. coeliac disease or Crohn's disease.
28
Causes of iron deficiency anaemia?
-Blood loss is the most common cause in adults
-Dietary insufficiency is the most common cause in growing children
-Poor iron absorption
-Increased requirements during pregnancy
29
Note:
The most common cause of iron deficiency anaemia in adults is blood loss. In menstruating women, particularly women with menorrhagia there is a clear source of blood loss. In women that are not menstruating or men the most common source of blood loss is the GI tract. It is important to be suspicious of a GI tract cancer. Oesophagitis and gastritis are the most common causes of GI tract bleeding. IBD should also be considered.
30
How does iron travel in the blood ?
As ferric ions (Fe3+) bound to transferrin.
31
What is the total iron binding capacity (TIBC) ?
It basically means the total space on the transferrin molecule for the iron to bind
32
How do you calculate transferrin saturation ?
Serum iron / total iron binding capacity
33
What is ferritin ?
The form that iron takes when it is deposited and stored in cells.
34
When is extra ferritin released from cells ?
In inflammation such as with infection or cancer
35
What does a low serum ferritin suggest ?
Highly suggestive of iron deficiency.
36
Note:
High ferritin is difficult to interpret and is likely to be related to inflammation rather than iron overload. A pt with a normal ferritin can still have iron deficiency anaemia, particularly if they have reasons to have a raised ferritin such as infection.
37
Serum iron varies significantly throughout the day with higher levels when ?
In the morning and after eating iron containing meals.
Note: On its own serum iron is not a very useful measure
38
Total iron binding capacity (TIBC) can be used as a marker for what ?
How much transferrin is in the blood.
Note: It is an easier test to perform than measuring transferrin
39
How do both TIBC and transferrin levels respond in iron deficiency and in iron overload ?
They both increase in iron deficiency and decrease in iron overload.
40
Note:
Transferrin saturation gives a good indication of the the total iron in the body. In normal adults it is around 30%.
41
What two things can increase the values of the previous tests mentioned giving the impression of iron overload ?
-Supplementation with iron
-Acute liver damage (lots of iron is stored in the liver)
42
Management of new iron deficiency in an adult without a clear underlying cause ?
New iron deficiency in an adult without a clear underlying cause e.g. menorrhagia or pregnancy should be investigated with suspicion. This involves doing an OGD and a colonoscopy to look for cancer of the gastrointestinal tract.
43
Management of iron deficiency anaemia (methods arranged from fastest to slowest and most invasive to least invasive) ?
1. Blood transfusion: This will immediately correct the anaemia but not the underlying iron deficiency and also carries risks.
2. Iron infusion e.g. "cosmofer": There is a very small risk of anaphylaxis but it quickly corrects the iron deficiency. It should be avoided during sepsis as iron "feeds" bacteria.
3. Oral iron e.g. ferrous sulphate 200 mg three times daily: This slowly corrects the iron deficiency. Oral iron causes constipation and black coloured stools. It is unsuitable where malabsorption is the cause of the anaemia.
Note: When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by around 10 grams/litre per week.
44
Pernicious anaemia is a cause of which type of anaemia ?
B12 deficiency anaemia
45
B12 deficiency anaemia can be caused by which two things ?
Insufficient dietary intake of vitamin B12 or pernicious anaemia.
46
Pathophysiology of pernicious anaemia ?
The parietal cells of the stomach produce intrinsic factor which is essential for the absorption of vitamin B12 in the ileum. Pernicious anaemia is an autoimmune condition where antibodies form against the parietal cells or intrinsic factor. A lack of intrinsic factor prevents the absorption of vitamin B12 and the pt becomes vitamin B12 deficient.
47
Vitamin B12 deficiency can cause neurological symptoms. Name some of these ?
-Peripheral neuropathy with numbness or paraesthesia
-Loss of vibration sense or proprioception
-Visual changes
-Mood or cognitive changes
48
Tom tip:
For your exams remember testing vitamin B12 deficiency and pernicious anaemia in pts presenting with peripheral neuropathy, particularly with pins and needles
49
Diagnosis of pernicious anaemia ?
Testing for auto-antibodies is used to diagnose:
-Intrinsic factor antibody is the first line investigation
-Gastric parietal cell antibody can also be tested but is less helpful
50
Management of pernicious anaemia ?
Note: Dietary deficiency can be treated with oral replacement with cyanocobalamin unless the deficiency is severe.
Pts can be treated with 1 mg of IM hydroxycobalamin 3 times weekly for 2 weeks, then every 3 months. More intense regimes are used where there are neurological symptoms.
Note: If there is also folate deficiency it is important to treat the B12 deficiency first before correcting the folate deficiency. Treating pts with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.
51
Haemolytic anaemia note:
There are a number of inherited conditons that cause RBCs to be more fragile and break down faster than normal, leading to chronic haemolytic anaemia. There are also a number of acquired conditions that lead to increased breakdown of RBCs and haemolytic anaemia
52
Inherited haemolytic anaemias ?
-Hereditary spherocytosis
-Hereditary elliptocytosis
-Thalassaemia
-Sickle cell anaemia
-G6PD deficiency
53
Acquired haemolytic anaemias ?
-Autoimmune haemolytic anaemia
-Alloimmune haemolytic anaemia (transfusion reactions and haemolytic disease of newborn)
-Paroxysmal nocturnal haemoglobinuria
-Microangiopathic haemolytic anaemia
-Prostatic valve related haemolysis
54
Features + explanation of haemolytic anaemia ?
The features are a result of the destruction of RBCs:
-Anaemia due to the reduction in circulating RBCs
-Splenomegaly as the spleen becomes filled with destroyed RBCs
-Jaundice as bilirubin is released during the destruction of RBCs
55
Investigations for haemolytic anaemia ?
-FBC shows a normocytic anaemia
-Blood film shows schistocytes (fragments of RBCs)
-Direct Coombs test is positive in autoimmune haemolytic anaemia.
56
What is hereditary spherocytosis + is it AD or AR ?
It is the most common inherited haemolytic anaemia in northern Europeans. It causes sphere shaped RBCs that are fragile and easily break down when passing through the spleen.
It is an autosomal dominant condition
57
How does hereditary spherocytosis present ?
It presents with jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of parvovirus.
58
Investigations for hereditary spherocytosis ?
It is diagnosed by FH and clinical features with spherocytes on the blood film. The MCHC is raised on a FBC. Reticulocytes will be raised due to rapid turnover of RBCs.
59
Management of hereditary spherocytosis ?
Treatment is with folate supplementation and splenectomy. Cholecystectomy may be required if gallstones are a problem.
60
Hereditary elliptocytosis ?
It is very similar to hereditary spherocytosis except that the RBCs are ellipse shaped. It is AD. Presentation and management are the same as hereditary spherocytosis.
61
What is G6PD deficiency ?
A condition where there is a defect in the RBC enzyme G6PD causing RBCs to break down early. Haemolytic crises can be triggered by infections, medications or fava beans (broad beans),
62
How does G6PD deficiency present + how is it diagnosed ?
It presents with jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on blood film. Diagnosis can be made doing a G6PD enzyme assay.
63
Medications that trigger haemolysis in G6PD deficiency ?
Primaquine, ciprofloxacin, sulfonylureas, sulfasalazine and other sulphonamide drugs.
64
TOM TIP:
The key piece of knowledge for G6PD deficiency relates to triggers. In your exam look out for a pt that becomes jaundiced and becomes anaemic after eating broad beans, developing an infection or being treated with antimalarials. The underlying diagnosis might be G6PD deficiency.
65
What are the two types of autoimmune haemolytic anaemia (AIHA) ?
-Warm type autoimmune haemolytic anaemia
-Cold type autoimmune haemolytic anaemia
66
Warm type autoimmune haemolytic anaemia:
The more common type of AIHA. It occurs at normal or above normal temperatures. It is usually idiopathic.
67
Cold type autoimmune haemolytic anaemia:
Also called cold agglutinin disease. At lower temperatures the antibodies against RBCs attach themselves to RBCs and cause them to clump together. This is called agglutination. This results in the destruction of RBCs as the immune system is activated against them and they get filtered and destroyed in the spleen.
68
Cold type AIHA is often secondary which conditions + infections ?
Lymphoma, leukaemia, SLE
Mycoplasma, EBV, CMV and HIV
69
Management of AIHA ?
-Blood transfusions
-Prednisolone
-Rituximab
-Splenectomy
70
What is alloimmune haemolytic anaemia + what are the two scenarios where this occurs ?
It occurs when there is either foreign RBCs circulating in the pts blood causing an immune reaction that destroys those RBCs or there is a foreign antibody circulating in their blood that acts against their own RBCs and causes haemolysis.
The two scenarios where this occurs are transfusion reactions and haemolytic disease of the newborn.
71
What happens in a haemolytic transfusion reaction ?
RBCs are transfused into the pt. The immune system produces antibodies against antigens on those foregin RBCs. This creates an immune response that leads to destruction of those RBCs.
72
What happens in haemolytic disease of the newborn ?
There are antibodies that cross the placenta from the mother to the fetus. These maternal antibodies target antigens on the RBCs of the fetus. This causes destruction of the RBCs in the fetus and neonate.
73
What is paroxysmal nocturnal haemoglobinuria ?
A rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone marrow occurs during the pts lifetime. The specific mutation results in a loss of the proteins on the surface of RBCs that inhibit the complement cascade. The loss of protection against the complement system results in activation of the complement cascade on the surface of RBCs and destruction of the RBCs.
74
Presentation of paroxysmal nocturnal haemoglobinuria ?
The characteristic presentation is red urine in the morning containing haemoglobin and haemosiderin. The pt becomes anaemic due to the haemolysis. They are also predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction)
75
Management of paroxysmal nocturnal haemoglobinuria ?
With eculizumab or bone marrow transplantation. Eculizumab is a monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system. Bone marrow transplantation can be curative.
76
What is microangiopathic haemolytic anaemia (MAHA) ?
It is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Imagine a mesh inside the small blood vessels shredding the RBCs.
77
MAHA is usually secondary to an underlying condition such as ?
-HUS
-DIC
-TTP
-SLE
-Cancer
78
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement. Basically the valve churns up the cells and they break down. What does the management involve ?
-Monitoring
-Oral iron
-Blood transfusions if severe
-Revision surgery may be required in severe cases
79
What is thalassaemia ?
It is related to a genetic defect in the protein chains that make up haemoglobin. Normally haemoglobin consists of 2 alpha and 2 beta globin chains. Defects in alpha globin chains lead to alpha thalassaemia. Defects in the beta globin chains lead to beta thalassaemia. Both conditions are AR. The overall effect is varying degress of anaemia dependant on the type and mutation
80
Why does thalassaemia result in splenomegaly ?
In thalassaemia the RBCs are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In thalassaemia the spleen collects all the destroyed RBCs resulting in splenomegaly.
81
Why does thalassaemia cause a susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences (cheek bones) ?
The bone marrow expands to produce extra RBCs to compensate for the chronic anaemia.
82
Potential signs and symptoms of thalassaemia ?
-Microcytic anaemia (low mean corpuscular volume)
-Fatigue
-Pallor
-Jaundice
-Gallstones
-Splenomegaly
-Poor growth and development
-Pronounced forehead and malar eminences
83
Diagnosis of thalassaemia ?
-FBC shows microcytic anaemia
-Haemoglobin electrophoresis is used to diagnose globin abnormalities
-DNA testing can be used to look for the genetic abnormality
Note: Pregnant women in the UK are offered a screening test for thalassaemia at booking.
84
Why does iron overload occur in thalassaemia, how is it checked and how is it managed?
As a result of faulty creation of RBCs, recurrent transfusions and increased absorption of iron in response to the anaemia.
Pts have their serum ferritin level monitored.
Management involves limiting transfusions and iron chelation.
85
Effects of iron overload in thalassaemia ?
Similar to haemochromatosis:
-Fatigue
-Liver cirrhosis
-Infertility and impotence
-Heart failure
-Arthritis
-Diabetes
-Osteoporosis and joint pain
86
What is alpha-thalassaemia caused by + which chromosome is this coding error on ?
Defects in the alpha globin chains. Chromosome 16.
87
Management of alpha-thalassaemia ?
-Monitoring FBC
-Monitoring for complications
-Blood transfusions
-Splenectomy may be performed
-Bone marrow transplant can be curative
88
What is beta-thalassaemia caused by + which chromosome is this coding error on ?
Defects in the beta globin chains. Chromosome 11.
89
Beta-thalassaemia note:
The gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta globin protein at all. Based on this, beta-thalassaemia can be split into three types:
-Thalassaemia minor
-Thalassaemia intermedia
-Thalassaemia major
90
What is beta thalassaemia minor, what type of anaemia does it cause and how is it managed ?
Pts with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
It causes a mild microcytic anaemia and usually pts only require monitoring and no active treatment.
91
What is beta thalassaemia intermedia, what type of anaemia does it cause and how is it managed ?
Pts have two abnormal copies of the beta globin gene. This can be either two defective genes or one defective + one deletion gene.
It causes a more significant microcytic anaemia (than thalassaemia minor).
Pts require monitoring and occasional blood transfusions. If they need more transfusions they may require iron chelation to prevent iron overload.
92
What is beta thalassaemia major, what does it cause and how is it managed ?
Pts are homozygous for the deletion genes. They have no functioning beta globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
It causes:
-Severe microcytic anaemia
-Splenomegaly
-Bone deformities
Management involves regular transfusions, iron chelation and splenectomy. Bone marrow transplant can be partially curative.
93
What is sickle cell anaemia ?
A genetic condition that causes sickle shaped RBCs. This makes the RBCs fragile and more easily destroyed, leading to a haemolytic anaemia.
94
Pathophysiology of sickle cell anaemia ?
It is an autosomal recessive condition where there is an abnormal gene for beta globin on chromosome 11. One copy of the gene results in sickle-cell trait. Pts with sickle-cell trait are usually asymptomatic. Two abnormal copies are required for sickle-cell disease.
Pts with sickle-cell disease have an abnormal varient of HbA called HbS. HbS causes RBCs to be an abnormal sickle shape
95
Why is sickle cell disease more common in pts from areas traditionally affected by malaria ?
Having one cop of the gene (sickle-cell trait) reduces the severity of malaria. Therefore pts with sickle-cell trait are more likely to survive malaria and pass on their genes.
96
How is sickle cell anaemia diagnosed ?
It is tested for on the newborn screening heel prick test at 5 days of age.
Also pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
97
9 complications of sickle cell anaemia ?
-Anaemia
-Increased risk of infection
-Stroke
-Avascular necrosis in large joints such as the hip
-Pulmonary HTN
-Priapism (painful and persistant penile erection)
-Chronic kidney disease
-Sickle cell crises
-Acute chest syndrome
98
General management of sickle cell anaemia ?
-Avoid dehydration and other triggers of crises
-Ensure vaccines are up to date
-Antibioitic prophylaxis to protect against infection with penicillin V
-Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of RBCs. This has a protective effect against sickle cell crises and acute chest syndrome.
-Blood transfusion for severe anaemia
-Bone marrow transplant can be curative.
99
What is a sickle cell crisis, how severe are they and how do they occur ?
An umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening. They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
100
What is a vaso-occlusive crisis (AKA painful crisis) in someone with sickle cell anaemia, what is it associated with, what are the symptoms and what can it cause ?
It is caused by sickle shaped blood cells clogging capillaries causing distal ischaemia.
It is associated with dehydration and a raised haematocrit.
Symptoms are typically pain, fever and those of the triggering infection.
It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis.
101
What happens in a splenic sequestration crisis, how is it managed + what prevents it?
It is a type of sickle cell crisis. It is caused by RBCs blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to severe anaemia and circulatory collapse (hypovolaemic shock).
Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises.
Note: Recurrent crisis can lead to splenic infarction and therefore susceptibility to infections.
102
What is an aplastic crisis, what is it most commonly triggered by, what does it lead to and how is it managed ?
It describes a situation where there is temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19. It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
103
What does a diagnosis of an acute chest syndrome require ?
-Fever or respiratory symptoms with
-New infiltrates seen on a chest xray
104
How can we categorise the causes of an acute chest syndrome ?
Infective (e.g. pneumonia or bronchiolitis) or non infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
105
An acute chest syndrome is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause with ?
-Antibiotics or antivirals for infections
-Blood transfusions for anaemia
-Incentive spirometry - using a machine that encourages effective and deep breathing
-Artificial ventilation - with NIV or intubation may be required
106
What are the four main types of leukaemia ?
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
107
Brief pathophysiology of leukaemia ?
Leukaemia is a form of cancer in the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cells.
The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types. This results in a pancytopenia.
108
What is a pancytopenia ?
A combination of anaemia, leukopenia and thrombocytopenia.
109
Mnemonic + ages at which the different types of leukaemia generally occur ?
ALL CeLLmates have CoMmon AMbitions
Under 5 and over 45 - acute lymphoblastic leukaemia (ALL)
Over 55 - chronic lymphocytic leukaemia (CeLLmates)
Over 65 - chronic myeloid leukaemia (CoMmon)
Over 75 - acute myeloid leukaemia (AMbitions)
110
Presentation of leukaemia ?
The presentation of leukaemia is quite non-specific. Some typical features are:
-Fatigue
-Fever
-Failure to thrive (children)
-Pallor due to anaemia
-Petechiae and abnormal bruising due to thrombocytopenia
-Abnormal bleeding
-Lymphadenopathy
-Hepatosplenomegaly
Note: If leukaemia appears on your list of differentials the get an urgent FBC
111
One of the key presenting features of leukaemia is bleeding under the skin leading to bruising and petechiae. This is caused by thrombocytopenia. It is important to be aware of the DD for this type of non-blanching rash, name 6 (you can include leukaemia)?
-Leukaemia
-Meningococcal septicaemia
-Vasculitis
-Henoch-Schonlein Purpura (HSP)
-Idiopathic Thrombocytopenia Purpura (ITP)
-Non-accidental injury
Note: Don't ever forgot NON-ACCIDENTAL INURY (abuse) as a differential, particularly in children and vulnerable adults
112
Investigations for leukaemia ?
-FBC - is the initial investigation. NICE recommend a FBC within 48 hours for pts with suspected leukaemia. Children or young adults with petechiae or hepatosplenomegaly should be referred immediately to hospital.
-Blood film - can be used to look for abnormal cells and inclusions
-LDH - is a blood test that is often raised in leukaemia but not specific to leukaemia. It can be raised in other cancers and many non-cancerous diseases.
-Bone marrow biopsy - main investigation for establishing a definitive diagnosis of leukaemia.
-CXR - may show infection or mediastinal lymphadenopathy
-Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma.
-Lumbar puncture - may be used if there is CNS involvement
-CT, MRI, and PET scans can be used for staging and assessing lymphoma for other tumours.
113
What are two types of bone marrow test used in diagnosing leukaemia and where are the biopsies taken?
-Bone marrow aspiration - involves taking a liquid sample full of cells form within the bone marrow.
-Bone marrow trephine - involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure
Bone marrow biopsies are usually taken from the iliac crest. It involves a local anaesthetic and a specialist needle.
Note: Samples from bone marrow aspiration can be examined straight away however a trephine sample requires a few days of preparation.
114
What happens in acute lymphoblastic leukaemia
There is a malignant change in one of the lymphocyte precursor cells. It causes ACUTE proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive proliferation of these cells cause them to replace the other cell types in the bone marrow, leading to a pancytopenia
115
What is the most common cancer in children + when does it peak ?
Acute lymphoblastic leukaemia and peaks around 2-4 years.
116
What is acute lymphoblastic leukaemia associated with + what would you see on a blood film.
Downs syndrome.
Blast cells.
117
What translocations is ALL associated with in children and adults ?
t(15:17) translocation in 30% of children with ALL
Philadelphia chromosome t(9:22) translocation in 30% of adults with ALL.
118
What happens in chronic lymphocytic leukaemia ?
This is CHRONIC proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes.
119
How does chronic lymphocytic leukaemia present + what can it cause?
It is often asymptomatic but it can present with infections, anaemia, bleeding and weight loss.
It can cause warm autoimmune haemolytic anaemia.
120
What can CLL transform into + what is this called ?
Into high-grade lymphoma. This is called Richter's transformation.
121
What would a blood film show in CLL + why does this occur ?
Smear or smudge cells.
These occur during the process of preparing the blood film where aged or fragile WBCs rupture and leave a smudge on the film.
122
What are the different phases in chronic myeloid leukaemia and what happens in each ?
CML has three phases: the chronic phase, the accelerated phase and the blast phase.
The chronic phase can last 5 years, is often asymptomatic and pts are diagnosed incidentally with a raised WCC.
The accelerated phase occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood (10-20%). In the accelerated phase pts become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
The blast phase follows the accelerated phase and involves an even higher proportion of blast cells in the blood (> 30%). This phase has severe symptoms and pancytopenia. It is often fatal.
123
Cytogenic change characteristic of CML ?
The Philadelphia chromosome. It is a t(9:22) translocation.
124
What will a blood film show in acute myeloid leukaemia?
A high proportion of blast cells which can have auer rods inside their cytoplasm.
125
AML can be the result of transformation from which type of disorders + give a couple of examples ?
Myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis.
126
TOM TIP:
There are some key bits of information that you should learn to be able to spot which leukaemia is in the exam:
-Acute lymphoblastic leukaemia: Most common leukaemia in children. Associated with Downs syndrome.
-Chronic lymphocytic leukaemia: Most common leukaemia in adults overall. Associated with warm autoimmune haemolytic anaemia, Richter's transformation into lymphoma and smudge/ smear cells.
-Chronic myeloid leukaemia: Has three phases including a 5 year "asymptomatic chronic phase". Associated with the Philadelphia chromosome.
-Acute myeloid leukaemia: Most common acute adult leukaemia. It can be the result of a transformation from a myeloproliferative disorder. Associated with auer rods.
127
Management of leukaemia ?
Treatment will be coordinated by an oncology MDT. Leukaemia is primarily treated with chemotherapy and steroids.
Other therapies include:
-Radiotherapy
-Bone marrow transplant
-Surgery
128
Name 8 complications of chemotherapy ?
-Failure to thrive
-Stunted growth and development in children
-Infections due to immunodeficiency
-Neurotoxicity
-Infertility
-Secondary malignancy
-Cardiotoxicity
-Tumour lysis syndrome
129
What causes tumour lysis syndrome + what happens + what can help with this + what else can happen ?
It is caused by the release of uric acid from cells that are being destroyed by chemotherapy.
The uric acid can form crystals in the interstitial space and tubules of the kidneys and cause AKI.
Allopurinol and rasburicase are used to reduce the high uric acid levels.
Other chemicals such as potassium and phosphate are also released so these need to be monitored and treated appropriately.
High phosphate can lead to low calcium, which can have adverse effects, so calcium is also moniotred.
130
What are lymphomas ?
A group of cancers that affect the lymphocytes inside the lymphatic system. These cancerous cells proliferate within the lymph nodes and cause the lymph nodes to become abnormally large (lymphadenopathy).
131
Two main categories of lymphoma ?
Hodgkin's lymphoma - is a specific disease
non-Hodgkin's lymphoma - encompasses all the other lymphomas
132
Hodgkin's lymphoma is caused by proliferation of lymphocytes. At what age does it tend to affect people ?
There is a bimodal age distribution with peaks around aged 20 and 75 years.
133
Risk factors for Hodgkin's lymphoma ?
-HIV
-Epstein-Barr Virus
-Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
-Family history
134
Presentation of Hodgkin's lymphoma ?
LYMPHADENOPATHY is the key presenting symptom. The enlarged lymph node or nodes might be in the neck, axilla or inguinal region. They are non-tender and feel "rubbery". Some pts will experience pain in the lymph nodes when they drink with alcohol.
B symptoms are the systemic symptoms of lymphoma:
-Fever
-Night sweats
-Weight loss
Other symptoms can include:
-Fatigue
-Itching
-Cough
-SOB
-Abdominal pain
-Recurrent infections
135
Investigations for Hodgkin's Lymphoma (include the key diagnostic test + what you would be looking for on this test)?
-LDH - is a blood test that is often raised in Hodgkin's lymphoma but is not specific and can be raised in other cancers and many non-cancerous diseases.
-Lymph node biopsy - is the key diagnostic test
-The Reed-Sternberg cell is the key finding from the lymph node biopsy in pts with HL. They are abnormally large B cells that have multiple nuclei that have nucleoli inside them. They look like the face of an owl with large eyes.
-CT, MRI and PET scans can be used for diagnosing and staging lymphomas and other tumours
136
What is the staging system used for Hodgkins and NH lymphoma + give a simplified version of it ?
The Ann Arbor staging system.
Stage 1: Confined to one region of lymph nodes
Stage 2: In more than one region but on the same side of the diaphragm (either above or below)
Stage 3: Affects lymph nodes both above and below the diaphragm
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver
137
Management of Hodgkin's lymphoma ?
The key treatments are chemotherapy and radiotherapy.
Note: The aim of treatment is to cure the condition. This is usually successful however there is a risk of relapse, other haematological cancers and side effects of medications.
Chemo creates a risk of leukaemia and infertility
Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism.
138
Name 3 notable Non-Hodgkin's lymphomas ?
-Burkitt lymphoma - associated with EBV, malaria and HIV
-MALT lymphoma - affects the MALT, usually around the stomach. It is associated with H. pylori infection
-Diffuse large B cell lymphoma - often presents as a rapidly growing painless mass in pts over 65 years
139
RF's for NHL include ?
-HIV
-EBV
-H. pylori (MALT lymphoma)
-Hep B or C infection
-Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes.
-FH
140
Presentation of NHL ?
Similar to HL and often they can only be differentiated when the lymph node is biopsied.
141
Management of NHL ?
Management involves a combination of treatments depending on the type and staging of the lymphoma:
-Watchful waiting
-Chemotherapy
-Monoclonal antibodies such as rituximab
-Radiotherapy
-Stem cell transplantation
142
What is a myeloma ?
A cancer of a specific type of B plasma cell. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.
143
What is multiple myeloma ?
Where the myeloma affects multiple areas of the body.
144
What is monoclonal gammopathy of undetermined significance (MGUS)
It is where there is an excess of a single type of antibody or antibody components without other features suggesting myeloma or cancer.
Note: This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear. It may progress to myeloma and pts are often followed up routinely to monitor for progression.
145
What is a smouldering myeloma ?
When there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS.
146
What is Waldenstrom's macroglobinemia ?
A type of smouldering myeloma where there is excessive IgM specifically.
147
Pathophysiology of myeloma ?
There is a genetic mutation in a specific type of plasma cell causing it to rapidly and uncontrollably multiply.
These cancerous plasma cells invade the bone marrow which is called bone marrow infiltration. This causes suppression of the development of other cell lines leading to anaemia, neutropenia and thrombocytopenia.
It also has other effects that will be discussed on different cards.
148
Antibodies are also called immunoglobulins. What are the 5 types of immunoglobulins ?
A G M D and E
149
When you measure the immunoglobulins in a pt with myeloma, one type of immunoglobulin will be significantly abundant. More than 50% of the time this will be which type ?
Type g (IgG)
150
What is the single type of antibody that is produced by all the cancerous plasma cells in myeloma called ?
A monoclonal paraprotein (this means a single type of abnormal protein)
151
When would you see a "Bence Jones protein" + what is it ?
It can be found in the urine of pts with myeloma
It is the light chains from the immunoglobulins produced by the cancerous plasma cells
152
Why does myeloma bone disease occur, where does it occur and what happens ?
It is the result of increased osteoclast and decreased osteoclast activity which is caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.
Common places for it to happen are the skull, spine, long bones and ribs. The abnormal bone mechanism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal. These patches of thin bone can be described as osteolytic lesions.
These weak points in bone lead to pathological fractures. For example a vertebral body in the spine may collapse (vertebral fracture) or a long bone such as the femur may break under minimal force.
Note: All the osteoclast activity results in hypercalcaemia.
People with myeloma can also develop plasmacytomas. These are individual tumours formed by cancerous plasma cells. They can occur in bones, replacing normal tissue or can occur outside bones in the soft tissues of the body.
153
Pts with myeloma often develop renal impairment. How can this happen ?
-High levels of immunoglobulins can block flow through the tubules
-Hypercalcaemia impairs renal function
-Dehydration
-Medications to treat the conditions such as biphosphonates can be harmful to the kidneys.
154
Why do you get hyperviscocity in myeloma + what issues can it cause ?
Plasma viscosity increases when there are more proteins in the blood. In myeloma there a large amounts of Igs in the blood which are proteins and cause the plasma viscosity to be significantly higher.
Issues:
-Easy bruising
-Easy bleeding
-Reduced or loss sight due to vascular disease in the eye
-Purplish discolouration to the extremities (purplish palmar erythema)
-Heart failure
155
Features of myeloma to remember for exams ?
CRAB
C - Calcium (elevated)
R - Renal failure
A - Anaemia (normocytic, normochromic) from replacement of bone marrow
B - Bone lesions and bone pain
156
RF's for myeloma ?
-Older age
-Male
-Black african ethnicity
-FH
-Obesity
157
When should you suspect myeloma + what initial investigations would you do ?
Anyone over 60 with persistent bone pain, particularly back pain, or an unexplained fracture.
Initial investigations:
-FBC (low WCC in myeloma)
-Calcium (raised in myeloma)
-ESR (raised in myeloma)
-Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected you should test further for myeloma (this will be on a different card)
158
Investigations for myeloma (testing not suspecting) ?
BLIP
B - (B)ence-Jones protein (request urine electrophoresis)
L - Serum free (L)ight-chain assay
I - Serum (I)mmunoglobulins
P - Serum (P)rotein electrophoresis
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more info on the disease.
Imaging is required to assess for bone lesions. The order of preference to establish this is:
1. Whole body MRI
2. Whole body CT
3. Skeletal survey (xray images of the full skeleton).
Pts only require one investigation but may not tolerate or be suitable for MRI or CT.
159
Name 3 Xray signs seen in pts with multiple myeloma ?
-Punched out lesions
-Lytic lesions
-"Pepperpot skull" caused by many punched out lesiosn throughout the skull
160
Management of myeloma ?
The aim of treatment is to control the disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life. Management will be undertaken by the haematology and oncology specialist MDT.
First line treatment involves a combination of chemotherapy with:
-Bortezomid
-Thalidomide
-Dexamethasone
Stem cell transplantation can be used as part of a clinical trial where pts are suitable
Pts require venous thromboembolism prophylaxis with aspirin or LMWH whilst on certain chemotherapy regimes as there is a higher risk of developing a thrombus
161
Management of myeloma bone disease ?
-Biphosphonates help suppress osteoclast activity.
-Radiotherapy to bony lesions can improve bone pain
-Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures
-Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain
162
Complications of myeloma + the treatments ?
-Infection
-Pain
-Renal failure
-Anaemia
-Hypercalcaemia
-Peripheral neuropathy
-Spinal cord compression
-Hyperviscocity.
163
Myeloproliferative disorders are considered a type of bone marrow cancer. Why do they occur ?
Due to uncontrolled proliferation of a single type of stem cell
164
The three myeloproliferative disorders to remember are ?
-Primary myelofibrosis
-Polycythaemia vera
-Essential thrombocythaemia
165
Primary myelofibrosis is the result of proliferation of which cell line ?
Haematopoietic stem cells
166
Polycythaemia vera is the result of proliferation of which cell line ?
Erythroid cell line
167
Essential thrombocythaemia is the result of proliferation of which cell line ?
Megakaryocytic cell line
168
Myeloproliferative disorders have the potential to progress and transform into what ?
Acute myeloid leukaemia
169
Myeloproliferative disorders are associated with certain genes, name three ?
JAK2 - most important
MPL
CALR
170
Myelofibrosis can be the result of primary MF, polycythaemia vera or essential thrombocythaemia. What happens ?
Proliferation of a cell line leads to bone marrow fibrosis. This is in response to cytokines that are released form the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and leukopenia.
When the bone marrow is replaced with scar tissue haematopoiesis starts to happen in other areas such as the liver and spleen. This is known as extramedullary haematopoiesis and can lead to hepatmegaly and splenomegaly. This can lead to portal HTN. If it occurs around the spine it can lead to spinal cord compression.
171
Presentation of the myeloproliferative disorders ?
Initially they can be asymptomatic.
They can present with systemic symptoms:
-Fatigue
-Weight loss
-Night sweats
-Fever
There may be signs and symptoms of underlying complications:
-Anaemia (except in polycythaemia)
-Splenomegaly (abdominal pain)
-Portal HTN (ascites, varices and abdominal pain)
-Low platelets (bleeding and petechiae)
-Thrombosis is common in polycythaemia and thromboythaemia
-Raised RBCs (thrombosis and red face)
-Leukopenia (infections)
172
FBC findings for the main myeloproliferative disorders ?
Polycythaemia vera:
-Raised Hb
Essential thrombocythaemia
-Raised platelet count
Myelofibrosis (due to primary MF or secondary to PV or ET) can give variable findings:
-Anaemia
-Leukocytosis or leukopenia (high or low white cell counts)
-Thrombocytosis or thrombocytopenia (high or low platelet count)
173
What would a blood film show in myelofibrosis ?
Teardrop shaped RBCs, anisocytosis (varying sizes of RBCs) and blasts (immature red and white cells).
174
Test of choice for establishing a diagnosis of a myeloproliferative disorder + what would this show + what test can help guide management ?
Bone marrow biopsy.
Bone marrow aspiration is usually "dry" as the bone marrow has turned to scar tissue.
Testing for JAK2, MPL and CARL genes can help guide management
175
Management of primary myelofibrosis ?
-Pts with mild disease with minimal symptoms might be monitored and not actively treated
-Allogenic stem cell transplantation is potentially curative but carries risks
-Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.
-Supportive management of the anaemia, splenomegaly and portal HTN
176
Management of polycythaemia vera ?
-Venesection can be used to keep the Hb in the normal range. This is the first line treatment.
-Aspirin can be used to reduce the risk of thrombus formation
-Chemotherapy can be used to control the disease
177
Management of essential thrombocythaemia ?
-Aspirin can be used to reduce the risk of thrombus formation
-Chemotherapy can be used to control the disease
178
What is myelodysplastic syndrome caused by + what happens ?
It is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
It causes low levels of blood components that originate from the myeloid cell line:
-Anaemia
-Neutropenia
-Thrombocytopenia
Note: There are a number of specific types of myelodysplastic syndrome
179
Who is myelodysplastic more common in + there is a risk it can transform into what ?
It is more common in pts above the age of 60 and in pts that have previously had treatment with chemotherapy or radiotherapy.
There is a risk of it transforming into acute myeloid leukaemia.
180
Presentation of myelodysplastic syndrome ?
Pts may be asymptomatic and incidentally diagnosed based on a FBC.
They may present with symptoms of anaemia (fatigue, pallor or SOB), neutropenia (frequent or severe infections) or thrombocytopenia (purpura or bleeding)
181
Investigations for myelodysplastic syndrome ?
FBC will be abnormal. There may be blasts on the blood film.
The diagnosis is confirmed by bone marrow aspiration and biopsy.
182
Management of myelodysplastic syndrome ?
-Watchful waiting
-Supportive treatment with blood transfusions if severely anaemic
-Chemotherapy
-Stem cell transplantation
183
Causes of thrombocytopenia (split causes up into appropriate categories) ?
Problems with production:
-Sepsis
-B12 or folic acid deficiency
-Liver failure causing reduced thrombopoietin production in the liver
-Leukaemia
-Myelodysplastic syndrome
Problems with destruction:
-Medications (sodium valproate, methotrexate, isotretinoin, antihistamines and PPIs)
-Alcohol
-Immune thrombocytopenic purpura
-Thrombotic thrombocytopenic purpura
-Heparin induced thrombocytopenia
-Haemolytic-uraemic syndrome
184
What is the normal platelet count ?
150 to 450 x 10^9/L
185
Presentation of thrombocytopenia ?
A mild thrombocytopenia may be asymptomatic and found incidentally on a FBC.
Platelet counts below 50 will result in easy or spontaneous bruising and prolonged bleeding times. They may present with nosebleeds, bleeding gums, heaving periods, easy bruising or blood in the urine or stools.
Pts with platelet counts below 10 are high risk for spontaneous bleeding. Spontaneous intracranial haemorrhage or GI bleeding are particularly concerning.
186
Differential diagnoses of abnormal or prolonged bleeding ?
-Thrombocytopenia
-Haemophilia A and haemophilia B
-Von Willebrand disease
-Disseminated intravascular coagulation (usually secondary to sepsis)
187
What is immune thrombocytopenic purpura (ITP)
A condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.
188
How is ITP managed ?
Management options include:
-Prednisolone
-IV immunoglobulins
-Rituximab (a monoclonal antibody against B cells)
-Splenectomy
Note: The platelet count needs to be monitored and the pt needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help. Additional measures such as carefully controlling BP and suppressing menstrual periods are also important.
189
What is thrombotic thrombocytopenic purpura + why does it happen ?
A condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affects the small blood vessels so it is described as a microangiopathy.
The blood clots develop due to a problem with a specific protein called ADAMTS13. This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in the small vessels. This causes platelets to be used up leading to thrombocytopenia. The blood clots in the small vessels break up RBCs, leading to haemolytic anaemia.
190
What causes deficiency in the ADAMTS13 protein ?
Either an inherited genetic mutation or autoimmune disease where antibodies are created against the protein
191
Treatment of thrombotic thrombocytopenic purpura ?
Treatment is guided by a haematologist and may involve plasma exchange steroids and rituximab (a monoclonal antibody against B cells)
192
What is heparin induced thrombocytopenia ?
A condition where there is development of antibodies against platelets in response to exposure to heparin. They specifically target a protein on the platelets called platelet factor 4 (PF4). These are anti-PF4/heparin antibodies.
The HIT antibodies bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state and leads to thrombosis. They also break down platelets and cause thrombocytopenia.
193
Diagnosis + management of heparin induced thrombocytopenia ?
Diagnosis is by testing for the HIT antibodies in the pts blood.
Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.
194
Von Willebrand disease (VWD) is the most common inherited cause of what ?
Haemophilia
195
Von Willebrand disease note:
VWD is the most common inhertied cause of haemophilia. There are many different genetic causes, most of which are autosomal dominant. The causes involve deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor. There are three types based on the underlying cause ranging from type 1 to type 3. Type 3 is the most severe.
196
Presentation of Von Willebrand disease ?
Pts present with a history of unusually easy, prolonged or heavy bleeding:
-Bleeding gums with brushing
-Epistaxis
-Menorrhagia
-Heavy bleeding during surgical operations
Note: FH of heavy bleeding or von Willebrand disease is very relevant
197
Diagnosis of VWD note:
Diagnosis is based on a history of abnormal bleeding, FH, bleeding assessment tools and laboratory investigations. Due to all the underlying causes there is no easy VWD test. This can make diagnosis challenging and beyond the scope of most medical exams.
198
Management of VWD (include the management of women with vWD that suffer with menorrhagia) ?
It does not require day to day treatment. Management is required either in response to major bleeding or trauma or in preparation for operations (to prevent bleeding):
-Desmopressin can be used to stimulates the release of vWF
-vWF can be infused
-Factor VIII is often infused along with plasma derived vWF
Women with vWD that suffer heavy periods can be managed by a combination of:
-Tranexamic acid
-Mefanamic acid
-Norethisterone
-COCP
-Mirena coil
Hysterectomy may be required in severe cases
199
What are haemophilia A and haemophilia B + what are they both caused by ?
They are inherited severe bleeding disorders.
Haemophilia A is caused by a deficiency in factor VIII
Haemophilia B is caused by a deficiency in factor IX
200
Both haemophilia A and B are X linked recessive. What does this mean ?
In order to have the condition all of the X chromosomes need to have the abnormal gene.
Men only have one X chromosome thus only need one abnormal copy to have the disease.
Women have two X chromosome thus need 2 to be affected (if they only have 1 they will be a carrier)
Therefore the disease mainly affects men.
201
How does haemophilia usually present + other signs and symptoms?
In neonates or early childhood. It an present with intracranial haemorrhage, haematomas and cord bleeding in neonates.
Haemoarthrosis and spontaneous bleeding into muscles are a classic feature of severe haemophilia. If untreated this can lead to joint damage and deformity.
Abnormal bleeding can occur in other areas:
-Gums
-GI tract
-Urinary tract causing haematuria
-Retroperitoneal space
-Intracranial
-Following procedures
Note: Pts can bleed excessively in response to minor trauma and are also at risk of spontaneous haemorrhage without any trauma.
202
Diagnosis of Haemophilia ?
Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing
203
Management of haemophilia ?
Management should be coordinated by a specialist.
The affected clotting factors (VIII or IX) can be replaced by intravenous infusions. This can be either prophylactically or in response to bleeding. A complication of this treatment is formation of antibodies against the clotting factor, resulting in the treatment becoming ineffective.
Treating acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:
-Infusions of the affected factor (VIII or IX)
-Desmopressin to stimulate the release of VWF
-Antifibrinolytics such as tranexamic acid
204
RF's for a DVT or PE ?
-Immobility
-Recent surgery
-Long haul flights
-Pregnancy
-Hormone therapy with oestrogen
-Malignancy
-Polycythaemia
-Systemic lupus erythematosus
-Thrombophilia
205
Thrombophilias are conditions that predispose pts to developing blood clots. Can you name some of these ?
-Antiphospholipid syndrome !!
-Antithrombin deficeincy
-Protein C or S deficiency
-Factor V Leiden
-Hyperhomocysteinaemia
-Prothrombin gene variant
-Activated protein C resistance
206
Every pt admitted to hospital should be assessed for their risk of VTE. If they are at increased risk of VTE they should receive prophylaxis with what + what would contraindicate these ?
LMWH such as enoxaparin. Contraindication include active bleeding or existing anticoagulation with warfarin or a NOAC.
Anti-embolic compression stockings are also used unless contraindicated. The main contraindication for compression stockings is significant peripheral arterial disease.
207
Presentation of a DVT + how would you examine for one ?
They are almost always unilateral. They can present with:
-Calf of leg swelling
-Dilated superficial veins
-Tenderness to the calf (particularly over the site of the deep veins)
-Oedema
-Colour changes to the leg
To examine for leg swelling measure the circumference of the calf 10cm below the tibial tuberosity. More than 3cm difference between calves significant.
Note: Always ask questions and examine with suspicion of a potentialy PE as well
208
What is the Wells score ?
It predicts the risk of a pt presenting with symptoms actually having a DVT or PE.
209
Investigations for a suspected DVT (include diagnosis)?
-D-dimer test
-US doppler of the leg - this is required to diagnose deep vein thrombosis. NICE recommend repeating negative US scans after6-8 days if there is a positive D-dimer and the Wells score suggest a DVT is likely.
Note: PE can be diagnosed with a CT pulmonary angiogram or VQ scan
210
Management of a DVT (both initial + longer term) ?
Initial management:
-Treat with LMWH. It should be started immediately before confirming the diagnosis in pts where DVT or PE is suspected and there is a delay in getting the scan
-Pts should then be switched to long term anticoagulation. Options for this are warfarin, a NOAC or LMWH
-LMWH is first line in pregnancy or cancer.
Continue anticoagulation for:
-3 months if there is an obvious reversible cause (then review)
-Beyond 3 months if the cause is unclear, there is recurrent VTE or there is an irreversible underlying cause such as thrombophilia. This is often 6 months in practice.
-6 months in active cancer (then review)
211
Name 2 examples of a LMWH ?
Enoxaparin and dalteparin
212
What is a D-dimer test, how can it be used and which conditions can cause it to be raised ?
It is a sensitive but not specific blood test for VTE.
This makes it useful for excluding VTE where there is a low suspicion. It is almost always raised if there is a DVT however other conditions can also cause it to be raised such as:
-Pneumonia
-Malignancy
-Heart failure
-Surgery
-Pregnancy
213
What are IVC filters + when are they used ?
They are devices inserted into the IVC designed to filter blood and catch any blood clots travelling from the venous system towards the heart and lungs. They act like a sieve, allowing blood to flow through whilst stopping larger blood clots.
They are used in unusual cases of pts with recurrent PEs or those that are unsuitable for anticoagulation
214
When pts have their first VTE without a clear cause, NICE recommend investigating them for possible cancer. To screen for cancer they recommend what ?
-History and examination
-Chest Xray
-Bloods (FBC, calcium and LFTs)
-Urine dipstick
-CT abdomen and pelvis in pts over 40
-Mammogram in women over 40
They also recommend testing for antiphospholipid syndrome by checking for antiphospholipid antibodies.
215
What is Budd-Chiari syndrome, how does it present and how is it managed ?
It is where a thrombosis develops in the hepatic vein, blocking the outflow of blood. It is associated with hyper-coagulable states. It causes an acute hepatitis.
It presents with a classic triad of:
-Abdominal pain
-Hepatomegaly
-Ascites
Management involves anticoagulation (heparin or warfarin), investigating for the underlying cause of hyper-coagulation and treating the hepatitis.
