Haem Flashcards
Define antiphospholipid syndrome
Characterized by the presence of antiphospholipid antibodies (APL) in the plasma, venous and arterial thromboses, recurrent foetal loss and thrombocytopenia.
Explain the aetiology / risk factors of antiphospholipid
syndrome
Difference between primary and secondary
Which individuals are susceptible
What is the genetic and environmental factors leading to the disease
What is the name of the main antiphospholipid antibody?
What is the effect of this antibody
Name another anti-phospholipid antibody
What other condition are these antibodies present in, and what is the implication of this?
What leads to -clotting -thrombocytopenia -anaemia in APS
AUTOIMMUNE
Antiphosholipid antibodies attack phosphilipids in the cell membrane, or plasma proteins bound to those anionic phospholipids.
Primary=happens by itself
Secondary=occurs with other AI diseases
APL may develop in susceptible individuals (e.g. those with rheumatic diseases e.g. SLE) following exposure to infectious agent –> secondary APS
Associated with mutated HLA-DR7 gene, allows production of APL antibodies
Once APL antibodies are present, second hit needed for development of syndrome (an environmental trigger)
Environmental triggers:
- Infections (syphilis, HIV, hep C, malaira)
- Drugs (CVS: procainamide, quiniine, propanalol, hydralazine; antipsychotics: phenytoin, chlorpromazine)
Main antiphospholipid antibody anti-beta2-glycoprotein I
This antibody targets anti-beta2-glcoprtein I, aka Apolipoprotein H. This lipoprotein usually inhibits agglutination
The procoagulant actions of APL is explained by their effect on b2 glycoprotein-I (clotting and platelet aggregation inhibitor), protein C, annexin V, platelets and fibrinolysis.
(remember that one of the key features of APS is arterial and venous thromboses)
Another anti-phospholipid antibody is anti-cardiolipin which targets the cardiolipin phospholipid in the inner mitochondrial membrane. This Ab is also present in syphilis, so having APS may lead to a false positive result for syphilis
See above for clotting, but autoantibodies targeting platelets and RBCs leads to thrombocytopenia and anaemia respectively.
Complement activation critical for pregnancy complications
Summarise the epidemiology of antiphospholipid syndrome
More common in young women
Accounts for 20% of strokes in < 45-yearolds and 27% of women with > 2 miscarriages.
Recognise the presenting symptoms of antiphospholipid syndrome
What is catastrophic antiphospholipid syndrome
Recurrent miscarriages (due to thrombosis leading to placental infarction),
history of arterial thromboses (stroke),
venous thromboses (DVT, pulmonary embolism),
renal failure (due to small capillaries, and the effects of clots here)
headaches (migraine),
chorea,
epilepsy
catastrophic antiphospholipid syndrome= rapid organ failure due to generalised thrombosis
Recognise the signs of antiphospholipid syndrome on physical examination
typical skin finding?
Livedo reticularis (swelling of venules due to obstructing clot).. appears as a mottled, purplish discolouration of skin
Signs of SLE (malar flush, discoid lesions, photosensitivity).
Signs of valvular heart disease (libman sachs endocarditis, see card below!)
Identify appropriate investigations for antiphospholipid syndrome and interpret the results
Diagnosis requires 1 clinical and 1 lab diagnosis criteria
Clinical criteria: 1. Hx thrombosis 2. Pregnancy complications
FBC (reduced platelets), ESR (usually normal), U&Es (APL nephropathy), clotting screen (raised APTT).
Presence of APL may be demonstrated by:
- ELISA testing for anticardiolipin and antib 2-GPI antibodies.
- Lupus anticoagulant assays: Clotting assays showing effects of APL on the phospholipiddependent factors in the coagulation cascade.
False-positive VDRL test for syphilis may be a clue to the presence of any type of APL.
Define haemolytic uraemic syndrome
Characterised by triad of:
- Microangiopathic haemolytic anaemia (it is one of the 3 causes, the other 2 are TTP and DIC)
- Thrombocytopenia
- Acute renal failure
The condition is categorised by whether it is associated with diarrhoea (D+, typical) or not (D-, atypical)
Epidemiology of HUS
Mainly children < 5 years of age
What causes haemolytic syndrome
1) Bacterial infection with E Coli O157:H7 (due to shiga like toxin), or shigella. This initially causes bloody diarrhoea too (D+). Infected from outbreaks after eating uncooked contaminated meat.
2) D negative form include pneumococcal lung infection, drugs (ciclosporin, some chemo agents), bone marrow transplant and pregnancy
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How does bacterial infection cause haemolytic uraemic syndrome
E Coli O157:H7 or shigella bind to intestinal wall and are picked up by white cells.
The kidneys have Gb3 receptor which picks up the antigens on the white blood cell. This causes death of the endothelial cells in the renal vasculature.
These dead endothelial cells are replaced by primary haemostasis with platelet plug, which then gets held together by fibrin.
Lots of endothelial cells die so there are lots of clots in the kidneys which consumes platelets. The deposited fibrin then slices RBCs up leading to MAHA.
There is also acute kidney injury
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Recognise the presenting symptoms of haemolytic uraemic syndrome
GI: severe abdominal colic, watery diarrhoea that becomes blood stained (due to the E Coli/shigella infection)
General: malaise, fatigue, nausea, fever <38 (in D+ form)
Renal: oliguria/anuria, haematuria
Recognise the signs of haemolytic uraemic syndrome on physical examination
General: Pallor (anaemia), slight jaundice (haemolysis), bruising (severe thrombocytopaenia), generalised oedema, HTN and retinopathy
GI: Abdo tenderness
Identify appropriate investigations for haemolytic uraemic syndrome and interpret the results
1st investigations:
FBC: anaemia, thrombocytopaenia
Peripheral blood smear:
To identify schichtocytes and to confirm the thrombocytopaenia
Renal function: Raised creatinine
Electrolytes: Abnormalities due to diarroeah or AKI. Include hyperkalaemia, hyponatraemia, acidosis etc.
PT, PTT: Both must be normal (if not, may suggest DIC)
Raised LDH from broken down RBCs
Low serum haptoglobin (it takes up haemolysed RBCs and then is removed by the liver/spleen)
Stool culture (SORBITOL-MACCONKEY AGAR) to detect shiga toxin producting E. Coli (needs to be done early in the course of diarrhoea though)
PCR to detect shiga toxin 1/2
Complement: abnormal levels of complement in familial and some cases of atypical HUS
The most common cardiac manifestation of SLE is
Pericarditis most common
Libman sacks endocarditis also common (this is also associated with antiphospholipid syndrome)
In antiphospholipid syndrome, who are arterial and venous thromboses more common in
What are the complications of each, generally and in APS
In APS there is a hypercoagulable state, causing thromboses in arteries and veins
Arterial thromboses more common in males.
Complications: heart attach, stroke, limb ischaemia
AND
(in APS) Libman Sacks endocarditis (vegetations (mixture of immune cells and blood clots) can affect the mitral valve)
Venous thrombosis more common in females. Typically present as DVT,
Complications: pulmonary embolism
Define vitamin B12
Which foods contain b12
Outline the normal absorption of b12
How much can the body store of b12
What is the job of b12
Reduced levels of vit b12 in the body
Present in egg, meat, milk but NOT in plants,
The protein containing the b12 is broken down using pepsin. It is then bound to IF (produced by gastric parietal cells). The b12-IF complex is recognised by the enterocytes lining the terminal ileum. Once absorbed, b12 is bound to transcobalamin
Body can store 4yrs of b12
Jobs:
- Allows conversion of dUMP to dTMP which is then converted into thymidine (essential for cell division)
- Also allows for conversion of homocysteine to methionine (too much homocysteine is harmful)
- Also helps to reduce methylmalonic acid
Explain the aetiology / risk factors of vitamin B12 deficiency
b12 deficiency results in reduced cell division and a build up of homocysteine and methylmalonic acid
BLOOD:
Macrocytes are produced which are destroyed in the spleen leading to anaemia, after which megaloblasts are released into the blood. Leads to macrocytic megaloblasic anaemia
Hypersegmented nuclei (>5 lobes)
Reduced production of megakaryocyte.
Can lead to pancytopenia (as can folate deficiency)
TONGUE:
Old epithelial cells aren’t replaced, reducing ability to heal when there is wear and tear of the tongue. This leads to inflammation= GLOSSITIS
ATHEROSCLEROSIS:
Homocysteine can bind to endothelial cells leading to proinflammatory cytokine release attracting immune cells. Narrowing of arteries and ischaemia. Homocysteine also increases increases platelet aggregation. So you are at increased risk of heart attack and stroke!
NEUROPATHY:
Methylmalonic acid can build up and accumulate in myelin sheaths, which causes it to degenerate. Can slow conduction in nerves and muscles. Subacute combined degeneration of the spinal cord
Reduced intake:
-(see above)
Reduced absorption:
-Crohn’s the enterocytes in terminal ileum might be damaged (so the b12 cannot bind to transcobalamin),
- Pernicious anaemia (IgA antibodies against IF OR the parietal cells),
- Gastric bypass (food passes through stomach quickly so IF can’t get to food to bind b12 fast enough) or gastric atrophy (reduced stomach acid production so not enough b12 is released)
- Diphyllobothrium latum (fish tapeworm) infestation/bacterial overgrowth
Risk factors:
Being long term vegan and not taking vit b12 supplements
What is subacute combined degeneration of spinal cord
Mix of UMN and LMN signs
UMN sign: symmetrical corticospinal tract loss, so causes UMN motor sign
LMN: Dorsal column loss causing LMN and sensory signs
Joint position and vibration affected first leading to ataxia followed by stiffness and weakness if untreated.
Classic triad: Extensor plantars (UMN), absent knee jerks (LMN) and absent ankle jerks (LMN)
Can present with falls at night time due to a combination of ataxia and reduced vision, which is also seen in b12 deficiency.
Pain and temperature may remain intact even in severe cases, as the spinothalamic tracts are preserved.
Recognise the presenting symptoms/signs of vitamin B12 deficiency
Anaemia:
-Pallor, SoB, easy fatigue
Soreness of tongue due to glossitis
Symptoms of IHD:
-chest pain, slurred speech, paralysis
Impaired neurological function:
-loss of memory function, reduced reflexes, psychosis
Identify appropriate investigations for vitamin B12 deficiency and interpret the results
Blood film (hypersegmented neutrophils, large RBCs)
MCV>100fL suggests macrocytosis
Bone marrow sample to look at megaloblastic changes in RBC precursors
Homocysteine and methylmalonic acid elevated
Look for anti-intrinsic factor antibodies for pernicious
Endoscopic or imaging if they could have crohn’s disease
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High homocysteine, normal methylmalonic acid
Folate.
B12 is required for homocysteine to metionine conversion AND
methamalonyl coA to succinyl CoA
Whereas Folate (b9) is only required for homocysteine to metionine conversion, so MMA is normal if there’s only a deficiency of folate
Define folate deficiency
=vitamin B9 deficiency
essential coenzyme that enables critical biochemical reactions (it makes purines and pyramidines)
What are the causes of folate deficiency
REDUCED DIETARY INTAKE
-Tea and toast diet
REDUCED ABSORPTION
- DRUGS: Phenytoin (inhibits intestinal conjugase which allows absorption), trimethoprim (inhibits dihydrofolate reductase), methotrexate, sulfasalazine and alcohol (sulfasalazine and alcohol inhibit the transporter which moves folate from the entereocyte into the portal vein)
- COELIAC, IBD
INCREASED REQUIREMENT:
-pregnancy, severe haemolytic anaemia
Which foods contain folate.
How does folate deficiency cause issues?
Dietary sources include naturally folate-rich foods such as leafy green vegetables, fruit and liver, but also supplements and fortified foods.
Malnutrition and excessive alcohol use are the most common causes of deficiency.
Folate deficiency causes impaired DNA synthesis, which leads to megaloblastic anemia. The clinical picture of anemia is similar to that of vitamin B12 deficiency, although folate deficiency is generally not associated with neurological manifestations.
Where is folate absorbed, where is it stored?
What is the active form of folate
Storage: liver (can store for up to 3 months)
Absorption: in the jejunum
Active form: tetrahydrofolate (THF), obtained after reduction of folate by dihydrofolate reductase.
Reduced THF due to reduced folate causes reduced DNA synthesis, megaloblastic erythropoiesis and anaemia.
Reduced methionine and increased homocysteine leads to endothelial damage and INCREASED RISK OF CARDIOVASCULAR DISEASE AND THROMBOEMBOLIC EVENTS
INCREASED RISK OF CANCER
Recognise the presenting symptoms of folate deficiency
Signs of anemia (e.g., fatigue, pallor)
Sore tongue (glossitis )
Recognise the signs of folate deficiency on physical examination
Glossitis
Fatigue, pallor
Identify appropriate investigations for folate deficiency and interpret the results
Diagnosis is based on laboratory findings such as macrocytosis, hyperhomocysteinemia, and normal levels of methylmalonic acid.
Folate serum levels not reliable
Hypersegmented neutrophils and pancytopenia may be present
What is the most definitive test of iron deficiency
The most definitive test of iron deficiency is a bone marrow biopsy. The bone marrow is part of the iron storage pool, and if a patient is truly iron-deficient, it will contain no stainable iron.
However, Serum iron is one of the key markers of iron depletion, and can therefore be used in the diagnosis of iron deficiency anemia, along with the serum ferritin level and total iron binding capacity.
Differentiate acute and chronic leukaemia
Acute leukaemia involve a proliferation of white cells that don’t mature at all, and these cells are usually in the blast form. Acute leukaemias come from less mature cells
(in the cell lineage tree, the higher up blast cell’s job physiologically is just to rapid divide to produce as many cells as possible that will later all differentiate, so a mutation in a gene in this cell type will result in a much more rapidly dividing leukaemia than the more mature precursor cells, which are more differentiated, and physiologically their function is to become a certain cell type, rather than just divide all the time)
Whereas chronic leukaemias involve proliferation of immature white cells, which have similar appearance to mature cells but lack functionality
(CLL is mature cells, CML is mixed mature and immature cells)
Outline the 3 types of genetic aberration that can result in leukaemia
1) Chromosomal deletions, where part of a chromosome is missing;
2) Trisomies, where there’s one extra chromosome; and
3) Translocations, where two chromosomes break and swap parts with one another.
How can you differentiate a leukaemia from a lymphoma
In leukaemia, the abnormal cells accumulate in the bone marrow or blood.
This differentiates them from lymphomas which can also arise from white blood cells, but they typically form solid tumors in lymphatic tissue such as lymph nodes, thymus, or spleen.
What causes anaemias, thombocytopaenia and leukopaenia in leukaemia
As these abnormal cells keep proliferating in the bone marrow, they take up a lot of space and this means that the other normal blood cells growing in the bone marrow get “crowded out”, resulting in cytopenias, including anemia, thrombocytopenia, and leukopenia.
Outline sites for deposition of leukaemia cells in the body
Some of them can deposit in organs and tissues throughout the body, like:
1) The liver and spleen causing hepatosplenomegaly, or
2) Lymph nodes causing lymphadenopathy, or
3) Skin causing purple or flesh colored plaques or nodules called leukemia cutis.
Differentiate the common age of presentation of AML vs ALL
AML is more common in older adults with a median age of 65 years, where as ALL is more common in children
What genetic abberation is AML usually caused by
AML is usually caused by chromosomal translocations, like translocation of chromosomes 15 and 17.
What genetic abberation is ALL usually caused by
ALL is also due to chromosomal translocations, like:
-translocation of chromosomes 12 and 21, or
!!!-translocation of chromosomes 9 and 22, also called the Philadelphia chromosome.
(note that the philadelphia chromosome is more known with CML but also occurs in CLL!)
Which genetic condition is associated with AML and ALL
A condition often associated with both AML and ALL is Down syndrome, which is caused by an extra chromosome 21.
A specific subset of AML is called acute promyelocytic leukaemia.
What is the genetic abnormality here and what are the effects
What is the treatment
Translocation between 15 and 17.
This disrupts the retinoic acid receptor alpha gene, which is needed for normal cell divsion
The treatment is all-trans retinoic acid, or vitamin A, and arsenic which induces the differentiation of promyelocytes.
What is AML with myelodysplasia
It’s a specific subtype of AML.
It happens when there is more than 20% blast cells.
It has poor prognosis
Risk factors for acute leukaemia
Finally, there are also some risk factors for acute leukemia like:
1) exposure to radiation, and
2) alkylating chemotherapy, which may have been used as a treatment for certain types of cancer.
In a pre-T cell ALL, where might the abnormal cells deposit
In the thymus or lymph nodes!
What is a haematological emergency that can result from acute promyelocytic leukaemia
The promyelocytes can activate the clotting process, further reducing platelets and leading to disseminated intravascular coagulation
What are the symptoms of ALL and AML
Which symtpoms are noted more in ALL?
What symptom is noted in the monocytic variety of AML
What symptom is noted in T-ALL
Fatigue (anaemia)
Easier bleeding (thrombocytopenia)
Increased infection (leukopenia)
Bone paina nd tenderness due to increased production
Abdominal fullness (hepatosplenomegaly)
Pain in lymph nodes (lymphadenopathy)
In ALL, these 2 are particularly noted:
Abdominal fullness (hepatosplenomegaly)
Pain in lymph nodes (lymphadenopathy)
In the monocytic variety of AML:
Swelling of gums due to monocytic enlargement
In t-ALL:
Mediastinal mass due to thymus enlargment
How are ALL and AML diagnosed
- Start with peripheral blood smear
- Myeloblasts in AML
- Lymphoblasts in ALL - Bone marrow biopsy
- Shows raised blast cells
What happens to the proportion of mast cells in acute leukaemia compared to normal person
Increases from 1-2% (normal) to >20% (acute leukaemia)
How can you differentiate AML from ALL?
AML:
- Myeloblasts are large
- Nuclei contain FINE chromatin with large nucleoli
- Can contain auer rods (particualry in acute promuyelocytic leukaemia) which are crystallised aggregates of the myeloperoxidase enzymes
ALL:
- Lymphoblasts are relatively smaller cells
- Nuclei containe COARSE chromatin which squash together to form small nucleoli
- Very little cytoplasm, which contains glycogen granules
What immunophenotyping markers suggests:
- ALL
- Specifically pre b cell
- TdT (which is a DNA polymerase ONLY in lymphoblasts)
- CD10 (surface marker)
Treatment for acute leukaemia
Reduce number of blast cell to allow other cells to develop normally
-AML and ALL treatmnet based on type and stage
Generally involves
-Chemo, biological, stem cell transplant, bone marrow transplant
Remember acute promyeloctic leukaemia can be treated with all-trans-retinoic-acid (ATRA)
It binds to the disrupted retinoic acid receptor and causes the blast to mature into neutrophils which go on to die, therefore cleaning out a lot of the blasts from the blood
How would you distinguish presentation of immune thrombocytopenia with AML? What about myeloma.
Immune thrombocytopenic purpura typically presents with bruising and bleeding with an isolated low platelet count.
Acute myeloid leukaemia frequently presents with bone marrow failure (which can be excess bleeding and bruising but with low plt Hb etc) with circulating blast cells in the peripheral blood.
In myeloma again pancytopenia can be part of the presenting picture but blast cells would not be seen in the peripheral blood
2 types of polycythaemia
Polycythaemia vera (a rare type of bone neoplasm resulting in a clonal proliferation of myeloid cells) and
Secondary polycythaemia (secondary to, for example, chronic hypoxia, renal tumours and erythropoietin abuse in athletes).
There is a strong association between polycythaemia vera and which other condition?
Myelofibrosis
What is the difference between TTP and HUS
Thrombotic thrombocytopaenic purpura (TTP) has the same features as HUS : 1) Acute renal failure, 2) Thrombocytopaenia and 3) MAHA)
With the addition of:
1) Fever and
2) Fluctuating neurological signs.
Define polycythaemia
Normal haematocrit is 45%. Polycythaemia is when there is increased concentration of RBCs in the blood (increased haematocrit)
Explain the aetiology / risk factors of polycythaemia
How is RBC production in the marrow usually controlled
Which mutation in which cells
- Polycythaemia vera: Increased blood cell levels due to overproduction by bone marrow
- Appropriate increase in erthyropoietin (chronic hypoxia e.g. high altitude, COPD, cyanotic heart disease
- Inappropriate increase in erythrypoietin (renal cell carcinoma/cysts, hepatoma, cerebellar haemangioblastoma, fibroids)
POLYCYTHAEMIA VERA:
Usually begins with mutation in haematopoietic stem cell.
90% of the time it’s a mutation in the janus kinase 2 (JAK2 gene).
RBC production is usually controlled by erythropoietin which activates JAK2 to switch on RBC production in HSC.
JAK2 is always on in the mutated version, leading to constant RBC production even without erythropoietin.
Eventually, the HSCs die out, and scar tissue forms. The bone marrow can no longer produce blood cells. This is known as a spent phase of polycythaemia vera. And at this point it’s really myelofibrosis.
Summarise the epidemiology of polycythaemia
.
Recognise the presenting symptoms of polycythaemia
What are they more prone to
Fatigue, dizziness, increased sweating, headaches, redness in the face, tinnitus, blurred vision,
and, perhaps the most memorable symptom, pruritus after a hot
bath.
MORE PRONE TO BLOOD CLOTS and their sequalae:
-stroke, heart attack, DVT, budd-chiari syndrome (when liver veins are blocked by a bloodclot)
Recognise the signs of polycythaemia on physical examination
Splenomegaly (excess RBCs build up in the spleen)
GOUT and KIDNEY STONES: due to to increased uric acid due to high turnover of RBCs
Identify appropriate investigations for polycythaemia (specifically vera here) and interpret the results
Blood test:
Increased Hb, haematocrit, increased WCC, increased platelet count
Decreased erythropoietin (but sometimes normal or elevated)
Bone marrow tissue examination/biopsy: look for fibrosis
Genetic testing: JAK2 testing
Brief treatment of polycythaemia
Phlebotomy (remove blood) every few months when there is lots of production
Myelosuppression:
- Hydroxyurea
- Ruxolitinib (JAK2 inhibitor)
In the spent phase may need blood transplants! (note these can actually come from autologous donation from their own blood previously removed and frozen after phlebotomy treatment)
Define myelofibrosis
The depletion of HSC and the formation of fibrotic/scar tissue in the bone marrow, in association with extramedullar haematopoiesis and splenomegaly
Explain the aetiology / risk factors of myelofibrosis
Primary:
A gene mutation within haematopoietic cells, usually JAK2 (gain of function, oncogene). Leads to proliferation of megakaryocytes in the bone marrow, which release cytokines including fibroblast growth factor which activates fibroblasts within the bone marrow. This is a myeloproliferative neoplasm
Secondary:
Essential thrombocythaemia
Polycythaemia vera
These are both also myeloprliferative neoplasms
*IMPORTANT! PLEASE NOTE THAT THE JAK2 MUTATION IS ACTUALLY COMMON TO PRIMARY MYELOFIBROSIS AND BOTH CAUSES OF SECONDARY MYELOFIBROSIS (ESSENTIAL THROMBOCYTHAEMIA AND POLYCYTHAEMIA VERA)
These both result in fibrosis which replaces normal bone marrow tissue, leading to pancytopaenia
The HSCs migrate to liver, spleen and lungs, and try to kick out blood cells, but often cannot compensate for the failure of medullary haematopoiesis, resulting in pancytopaenia
RISK FACTOR:
Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of primary myelofibrosis in a small number of cases.
Summarise the epidemiology of myelofibrosis
.
Recognise the presenting symptoms of myelofibrosis
Asymptomatic: diagnosed following abnormal blood count
Systemic symptoms:
Common- fatigue, weight loss, anorexia, itching, fever, night sweats
Uncommon: LUQ abdo pain, indigestion (caused by massive splenomegaly)
Bone pain, bleeding and gout are less common complaints
Recognise the signs of myelofibrosis on physical examination
Signs of extramullary haematopoiesis:
Splenomegaly is main finding (massive in 10%)
Hepatomegaly
Pulmonary HTN
Signs of pancytopaenia:
Leukopaenia –> frequent infections
Anaemia –> fatigue
XS platelets –> DVTs and pulmonary thomboembolisms
Identify appropriate investigations for myelofibrosis and interpret the results
What type of cells are seen in blood film
FBCs:
Initial increase in blood cells (in primary, especially platelets. Be careful to differentiate this from essential thrombocytopaenia, which is a secondary cause of myelofibrosis)
BUT there is then a drop due to pancytopaenia (as the fibrosis reduces medullary function)
LFT abnormal
Blood smear (i.e. the following cells are in the peripheral circulation, not bone marrow):
Abnormal, tear drop shaped RBCs (CALLED DACROCYTES);
Circulating immature, nucleated RBCs;
Immature WBCs and platelets
MARROW ASPIRATION/BIOPSY:
Early: increase in HSC numbers
Late: reduced HSC numbers and fibrosis
Aspiration usually unsuccessful (‘dry tap’). Trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining
What are the features of multiple myeloma
hyperCalcaemia (stones, bones, abdominal groans and psychiatric overtones)
Renal failure
Anaemia
Bone pain
=CRAB
What finding is seen on blood film in multiple myeloma
Rouleaux are stacks of red cells seen on a blood film,
which form due to the high concentration of plasma proteins (e.g. immunoglobulins)
and give rise to the high ESR.
In which type of disease are each of these cells seen on blood film:
Schistocytes
Granulocytes with absent granulation/hyposegmented neutrophils
Dacrocytes
Smear cells
Schistocytes, also known as red cell fragments, are an indicator of intravascular
haemolysis.
Granulocytes with absent granulation and hyposegmented nuclei are
found in myelodysplastic syndrome.
Dacrocytes are teardrop-shaped cells seen in
myelofibrosis.
Smear cells are seen in chronic lymphocytic leukaemia.
Hx in ALL
Symptoms of bone marrow failure:
Anaemia (fatigue,dyspnoea)
-Bleeding(spontaneous bruising, bleeding gums, menorrhagia),
-Opportunistic infections (bacterial, viral, fungal, protozoal).
Symptoms of organ infiltration:
- Tender bones, enlarged lymph nodes, mediastinal compression (in T cell ALL)
- Headache, visual disturbance, nausea (meningeal involvement)
Examination in ALL
Signs of BM failure:
- Pallor
- Bruising, bleeding
- Infection (fever, GI, skin, resp problems)
Signs of organ infiltration:
Lymphadenopathy, hepatosplenomegaly, cranial nerve palsies,
retinal haemorrhage or papilloedema on fundoscopy,
leukaemic infiltration of the anterior chamber of the eye (mimics hypopyon),
testicular swelling.
Investigations for ALL.
What would be seen on:
Blood tests
Blood film
Bone marrow aspirate?
Immunophenotyping?
Cytochemistry?
Bone radiograph?
Bloods:
- Normochromic, normocytic anaemia
- Reduced platelets
- Variable WCC
- Raised uric acid
- Raised LDH
Blood film:
-Lymphoblasts (in the periphery)
Bone marrow aspirate: hypercellular with >30% lymphoblasts
Immunophenotyping:
Using antibodies for cell surface antigens e.g. CD20.
Cytochemistry:
PAS stain positive: B cell lineage
Acid phosphatase positive: T cell lineage
Bone radiograph:
Mottled appearance with ‘punched-out’ lesions (e.g. skull caused by leukaemic infiltration
What is the morphologic classification of ALL
L1: Small lymphoblasts, scanty cytoplasm.
L2: Larger, heterogenous lymphoblasts.
L3: Large lymphoblasts with blue or vacuolated cytoplasm.
Why might you do a chest x ray in ALL
May show mediastinal lymphadenopathy, thymic enlargement (in T cell lineage ALL), lytic bone lesions.
Which conditions is ALL assocaited with
Environmental (radioation viruses)
Genetic (down syndrome, neurofibromatosis type 1, fanconi’s anaemia, achondroplasia, ataxia telangiectasia, xeroderma pigmentosum)
How is AML classified
Into 8 morphological variant using the FAB systems.
M0: Myeloblastic. No Maturation
M1 Myeloblastic with little maturation.
M2 Myeloblastic with maturation.
M3 Promyelocytic with coarse cytoplasmic granules.
M4 Granulocytic and monocytic differentiation (myelomonocytic).
M5 Monoblastic differentiation.
M6 Erythroblastic differentiation.
M7 Megakaryoblastic.
Which morphologic variant contains Auer rods
What is this variant associated with
M3 Promyelocytic with coarse cytoplasmic granules. Characteristic Auer rods (crystallisation of granules resembling bundle of sticks or ‘faggots’).
Associated with DIC and IC haemorrhage
Symptoms of AML
Symptoms of bone marrow failure:
- Anaemia (lethargy, dyspnoea)
- Bleeding (thrombocytopaenia OR DIC)
- Infections
Symptoms of tissue infiltration:
- GUM SWELLING OR BLEEDING (in M4)
- CNS involvement (headache, nausea, diplopia) in M4 and M5 especially
What is the cause of bleeding in AML
Thrombocytopaenia due to bone marrow failure
OR
DIC, especially in M3 variant
AML on examinaion
Signs of bone marrow failure:
- Pallor, cardiac flow murmur
- Ecchymoses and bleeding
- Infections
Signs of tissue infiltration
- Skin rashes, gum hypertrophy,
- Deposit of leukaemic blasts may rarely be seen in the eye (chloroma), tongue and bone–in the latter may cause fractures.
AML investigations:
What would be seen on:
Blood tests
Blood film
Bone marrow aspirate?
Immunophenotyping?
Immunocytochemistry?
Blood tests
- Low Hb and platelets, variable WCC.
- High uric acid and LDH
- May do fibronigen and d dimers when DIC is suspected in M3.
Blood film
- AML blasts with cytoplasmic granules
- Auer rods in M3
Bone marrow aspirate
Hypercellular with >30 % blasts (immature cells)
Immunophenotyping
Antibodies against surface antigens to classify lineage of abnormal clones.
Immunocytochemistry:
- Myeloblast granules are positive for Sudan Black, choroactetate esterase and myeloperoxidase
- Monoblasts are positive for non-specific and butyrate esterase
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