Haematology Flashcards
The main component involved in stabilising the primary haemostatic plug.
Fibrin
A serine protease which assists in the break down of blood clots by binding to the clot and localising agents which break it down.
Tissue plasminogen-activator (t-PA)
A potent inhibitor of plasmin in the blood.
a2 macroglobulin
Alpha 2 macroglobulin acts as an antiprotease and is able to inactivate an enormous variety of proteinases. It functions as an inhibitor of fibrinolysis by inhibiting plasmin and kallikrein. It functions as an inhibitor of coagulation by inhibiting thrombin.
A single chain glycoprotein, synthesised by the liver and endothelium, which has strongly anticoagulant action and is important in the mode of action of heparin.
Antithrombin III
It is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots.
plasmin
This product of the cyclic endoperoxides induces platelet aggregation
Thromboxane A2
A 6 foot 7 inch rower presents to his GP complaining of easy skin bruising. On further examination he is found to have pectus excavatum, lax joints and a high-arched palate.
Ehlers-Danlos syndrome
A 62 year old overweight woman presents to the Emergency Department following a Road Traffic Accident. A full set of investigations is carried out – which shows an increased Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT)/INR
vitamin K deficiency
A 25 year old man presents to the Emergency Department a day after attending his dentist for a routine check-up. After treatment at the dentists the previous day, his gums had not stopped bleeding. On investigation, his APTT and bleeding time are prolonged but a normal PT.
von Willebrand deficiency
↓ platelet function and ↓ factor VIII (vWF carries factor VIII in circulation)
o Mostly autosomal dominant affecting 1/10,000 o Presentation: often bleeding indicative of platelet disorders (i.e. mucocutaneous bleeding) but can also include bleeding indicative of coagulation disorders
o Diagnosis:↑APTT, ↑bleedingtime
↓FactorVIII,↓vWFAg. NormalINR&plts o Management:Desmopressin,VWFandFactorVIIIconcentrates
A 16 year old girl presents to the Haematology Outpatients clinic describing a fluctuating history of easy bruising, epistaxis and menorrhagia.
On investigation there is:
- a thrombocytopaenia with increased megakaryocytes on BM examination.
- ATP
- Glycoprotein IIb/IIIa on platelets
- Anti Platelet Antibody Steroids
- IVIG
- Anti-D Antibody,
Factor VIII deficency
Hemophila A X-linked recessive affecting 1/10,000 males
o Presentation: often early in life or prolonged bleeding after surgery/trauma
o Diagnosis: ↑APTT, normal PT and ↓ factor VIII assay.
oManagement:AvoidNSAIDsandI
Minjections,desmopressin(vWFrelease which is VIII carrier), factor VIII concentrates as replacement which is life long
Factor IX
Chrismas Diseases X-linked recessive affecting 1/10,000 males o Presentation: often early in life or prolonged bleeding after surgery/trauma o Diagnosis: ↑APTT, normal PT and ↓ factor IX assay. o Severity:relatedtofactorleveleg.sev<1%,mod1-5%,mild5-25% o Management:AvoidNSAIDsandIMinjections,desmopressin(vWFrelease which is VIII carrier), factor VIII concentrates as replacement which is life long
It inhibits platelet activation and is also an effective vasodilator.
Prostacylin
Which protein, important in haemostasis, is vitamin K dependent but is not a serine protease? Which option is required as a cofactor for protein C activity?
What does it do?
Protein S
Inhibits factor Va and XIII
Which option synthesises TF, vWF, prostacyclin, plasminogen activator, antithrombin III and thrombomodulin?
Vascular endothelium
Which enzyme, important for platelet aggregation, is irreversibly inhibited by aspirin?
Cyclooxygenase
Which key clotting factor activates both factors V and VIII, and also activates protein C?
Thrombin
can reversibly inhibit Factor Xa
While Xa is inhibited, the Xa- “ XXXX’’ complex can subsequently also inhibit the FVIIa-TF complex.
Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit Factor Xa (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa-tissue factor complex.
It connects intrisinc and extrinsinc pathway
Factor X
22 year old Saharawi refugee presents with anaemia, weight loss, loose stools (malnutrition vitamins ADEK and blood tests reveal an increased PT/INR and slightly increased APTT, with normal thrombin time and platelet count.
vitamin K deficiency
- increased PT/INR = vitamin K
A 5 year old boy has the following blood results: normal PT, increased APTT, normal platelet count, decreased VIII:C and decreased vWF.
vWF The most common hereditary bleeding disorder, affect 1% of the population. vWF is a carrier protein for factor VIII and stabilises it. Mutation is in chromosome 12
A 32 week pregnant lady who has gestational diabetes and is epileptic has a caesarean section while on holiday in rural China. Her newborn baby is suffering from bleeding from the umbilical stump, as well as nose and gums. What is wrong with the baby?
vitamin K deficiency- babies in the UK are given vitamin K post-birth
IgA mediated vasculitis In children < 10 years Preceding URTI Palpable purpuric rash (lower libs extensors + buttocks) Colicky abdo pain Glomerulonephritis Arthritis Orchitis
HSP
Skull bossing, maxillary hypertrophy, hairs on end skull X-ray, Hepatosplenomegaly
β Thalassaemia:
o β- thalassaemia major (homozygous) → 3-6mths severe anaemia, FTT, hepatosplenomegaly (extramedullary erythropoiesis), bony deformity, severe anaemia + heart failure
Diagnosis: Hb electrophoresis (Guthrie at birth) Treatment: blood transfusions and desferrioxamine to stop iron overload, plus folic acid
Point mutations – ↓ β-chain synthesis (spectrum of disease), excess α-chains ↑HbA2 and HbF
o β- thalassaemia minor (heterozygous) → Asymptomatic carrier, mild anaemia
Features mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate** to the anaemia **HbA2 raised (> 3.5%)
β Thalassaemia minor
A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods.
A rare autosomal dominant disorder. Alternative name = HHT
There is a structural abnormality of the blood vessels, resulting in telangiectases, which are thin walled so are likely to bleed. This leads to haemorrhage and anaemia. It is more common in females, and may not present until later in life.
Epistaxis is the commonest presenting symptom. This patient is feeling tired, not just because of her 4 children, but because she also has iron deficiency anaemia
A fit 48-year-old investment banker presents to A&E with a painful R arm that was present when he woke up that morning. He is otherwise well and there is no history of trauma or abnormalities of any system. On examination there is marked tenderness and mild erythema along the anterolateral aspect of the forearm and cubital fossa, with no abnormality of the upper arm or axilla.
Superficial venous thrombosis
A 45-year-old lady, known heavy smoker with chronic respiratory problems, presents to her GP with increasing dyspnoea and swelling of her R arm and face.
On examination of her chest there is no asymmetry or tracheal deviation, but there are added sounds over the R upper lobe and on bending forward her face becomes congested.
Superior vena caval obstruction
A 56-year-old woman returns to the Vascular Clinic with recurrence of her L leg ulcer after the area has been knocked by a shopping trolley.
On examination the ulcer is situated above the medial malleolus, its dimensions being 6cm x 5cm. The base is filled with yellowish slough and the surrounding area is erythematous, with prominent oedema.
Postphlebitic syndrome
Post-thrombotic syndrome (PTS), also called postphlebitic syndrome and venous stress disorder is a medical condition that may occur as a long-term complication of deep vein thrombosis (DVT).
A 48-year-old man develops R-sided pleuritic chest pain and coughs-up a trace of bloodstained sputum 8 days after a R hemicolectomy.
He has mild dyspnoea but chest examination and chest radiography are normal.
Pulmonary embolism
A 32-year-old lady develops acute swelling of her L leg 2 days post-partum. She had bilateral leg swelling during the pregnancy but the delivery was normal. On examination there is tense swelling of the leg and thigh and some deep tenderness over the calf and medial aspect of the thigh.
DVT
Trousseau’s syndrome (25%)- recurrent superficial thrombophlebitis is associated with which pathology?
pancreatic cancer
Patients presenting with malignancy, sepsis, trauma, obstetric complications, toxins.
Low plts, low fibrinogen, high FDP/ddimer, long PT/INR
(low platelets - high evrything else)
Acquired: Disseminated intravascular coagulation (DIC):
o Widespreadactivationofcoagulation
o Clotting factors and platelets are consumed → ↑ risk of bleeding
o Treat the cause and give transfusions, FFP, platelets, cryo etc
A drug that is administered intravenously and has a rapid effect by potentiating the action of antithrombin. Action can be reversed quickly which is of relevance in myocardial infarction patients who may require early invasive treatment (ie PTCA).
Unfractionated heparin (UFH)
Potentiates antithrombin III. Usually given subcutaneously. Can cause osteoporosis and hyperkalaemia.
Dalteparin (LMWH)
Used to monitor patients undergoing warfarin therapy.
PT, monitor wafarin therpahy, starts with factor VII
Used to monitor patients undergoing unfractionated heparin therapy.
APTT, used to monitor heparin theraphy. Starts with factor XII
This anticoagulant drug is directly contraindicated in pregnancy, especially the first 16 and last 4 weeks of a 40 week gestation.
Warfarin
Warfarin is an oral anticoagulant which inhibits the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C!!!!!!
teratogenic, although can be used in breast-feeding mothers
Reflects the amount and activity of fibrinogen.
Thrombin time (TT) as Thrombin converts Fibrnogen to Fibrin
Antiplatelet action. Indicated for primary prophylaxis of stroke in a patient experiencing recurrent retinal TIAs (amaurosis fugax). Ineffective for DVT prophylaxis.
Aspirin
Aspirin works by blocking the action of both cyclooxygenase-1 and 2. Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis.
Antiplatelet action. Licensed for secondary prophylaxis of stroke. More effective than aspirin alone.
Dipyridamole modified release (MR) and aspirin
Dipyridamole
Dipyridamole is an antiplatelet mainly used in combination with aspirin after an ischaemic stroke or TIA
Mechanism of action
inhibits phosphodiesterase, elevating platelet cAMP levels which in turn reduce intracellular calcium levels
other actions include reducing cellular uptake of adenosine and inhibition of thromboxane synthase
Antiplatelet action. clopidogrel is also now first-line in patients following an ischaemic stroke and in patients with peripheral arterial disease.
Clopidogrel antagonist of the P2Y12 adenosine diphosphate (ADP) receptor, inhibiting the activation of platelets
Dangerous combination with no added efficacy and increased GI bleed.
Clopidogrel and aspirin
Old model of starting warfarin
. 10mg, 10mg, 5mg, measure on 4th day then every 2 days
New (recommended, Tait) model of starting warfarin
5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days
In patients with metallic heart valves, this drug is the most effective anticoagulant
Warfarin
In patients with cancer and acute venous thromboembolism, the most effective drug at reducing the risk of recurrent VTE is __?
Dalteparin (LMWH)
This drug when given alone initially increases the clotting risk
Warfarin
Side effects include cutaneous necrosis
Warfarin
The drug most likely to cause thrombocytopaenia with paradoxical thrombosis - remember HIT the Wafarin!!!
Unfractionated heparin (UFH)
SE:
Bleeding
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis
Indicated as thrombotic prophylaxis in DIC
Dalteparin (LMWH)
Contra-indicated if recent sore throat, if ever used before, or in the presence of proliferative retinopathy.
Streptokinase
A 65 year old patient presents with hepatosplenomegaly. He is mildly anaemic and thrombocytompenic. A blood monocyte count of 1.2 x 109/l is observed. Bone marrow aspirate reveals ring sideroblasts at 15% of total blasts. Auer rods are observed.
Chronic Myelomonocytic Anaemia
An alcoholic presents to your clinic with anaemia. Sideroblasts are observed on morphological examination.
What is it caused by??
Secondary Sideroblastic Anaemia
Ineffective erythropoiesis → iron loading (bone marrow) causing haemosiderosis
(endocrine, liver and cardiac damage due to iron deposition)
Diagnosis: Ring sideroblasts seen in the marrow (erythroid precursors with iron
deposited in mitochondria in a ring around the nucleus).
Causes: myelodysplastic disorders, following chemotherapy, irradiation, alcohol
excess, lead excess, anti-TB drugs or myeloproliferative disease.
Treatment: Remove the cause and Pyridoxine (vitamin B6 promotes RBC production).
A 58 year old lady complains of lethargy and “easy bruising”. She presents with purpura. Her FBC reveals Hb 10.5g/dl; WBCs 2.3x109/l and platelets 8x109/l. Blood film reveals <1% Blasts, and marrow aspirate shows 20% dysplasia in erythroid lineage, 60% dysplasia in platelet lineage, 5% dysplasia in granulocyte lineage, and less than 5% blasts.
Refractory Cytopaenia with Multilineage Dysplasia
1) Why? this patient is tired, easy bruisng, fatique.
2) Bone marrow aspirate indicates dysplasia in different linages of the blood
A 78 year old male patient with recurring infections of the face and maxillary sinuses associated with neutropenia. His bloods are: Hb 9.8 g/dl; WBC 1.3x109/l; Neutrophils 0.3x109/l; platelets 38x109/l.The lab informs you that there are Blasts approximately compromise 17% of bone marrow aspirate.
Again, this patien is eldery, presents with reccurent infections and excess blast.
Refractory Anaemia with excess of Blasts II
You are called to A&E to see a 65 year old man. He is complaining of fever, shortness of breath, and has lost 5Kg in the last few months. His notes say he was previously diagnosed with “Refractory Anaemia with excess Blasts in Transformation” (RAEB-t). His blast cell count is approximately 30% of all nucleated cells.
Acute Myeloid Leukaemia
A 74 year old woman with high-normal platelet count. Bone marrow aspirate shows hyperplasia of hypolobulated micromegakaryocytes. Responds well to lenalidomide.
Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)
A 34 year old man with peripheral cytopenia suffers from bleeding gums. Peripheral blood shows 5% blast cells and bone marrow 42% blast cells.
Acute Myeloid Leukaemia
As listed above, plus:
Lymphadenopathy less common
Quick subtype facts:
M3: Acute promyelocytic
leukaemia – prone to DIC
M4+5: Monoblasts/monocytes -
Skin / gum infiltration +
hypokalaemia
High WCC
Auer rods and granules
Myeloperoxidase and Sudan black
B stains
A 20 year old man with hepatitis C complains of fatigue and breathlessness and bruises very easily.
secondary aplastic anemia
why?
Fatigue-breathlessnes and easy brusing are common indication of the bone marrow problem.
Fatigue (RBC) and platlets (low)- brusing.
This patinet also has Hep C, which causes the aplastic anemia
This patients blood film shows classic Pelger-Huet neutrophils and bone marrow blasts make up 15% of cells.
Refractory anaemia with an excess of blasts
In this case haemoglobin is normal but there is a reduction in platelets and neutrophils
Refractory cytopenia with multilineage dysplasia
A 64 year old man complains of headaches, fatigue and itchy skin, particularly evident after a hot bath. He has a long-standing history of alcohol abuse and drug history reveals that he taking thiazide diuretics. On examination, you note that he is thin with sunken eyes.
Pseudopolycythaemia- dehydration
A 55 year old female has a past medical history of deep vein thrombosis. She also complains of easy bruising. Her platelet count is 770 x109/L, CRP is 4mg/L. You prescribe aspirin.
Essential thrombocythaemia
is a rare chronic blood disorder characterised by the overproduction of platelets by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukaemia or myelofibrosis.
A 53 year old man goes to see his doctor about an embarrassing problem. It seems that his friends have nicknamed him ‘Rudolph’. You seem quite confused, but all becomes apparent when he points to his nose, which appears red. After further questioning, he describes a ‘burning’ sensation on his nose, hands and feet and visual disturbances. You send him for ‘blood tests’. What do you expect to be raised?
Haematocrit
A consultant grills you on a ward round: there is a patient with a WBC of 140 x109/L, Hb 12 g/dL, Platelet count 320 x109/L. She complains of tiredness, night sweats, fever and abdominal pain. Her spleen is markedly enlarged. Blood film shows blasts, neutrophils, basophils. How would you treat her?
Imitanib
Chronic Myeloid Leukaemia
Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)
PCR for BCR-ABL (Philadelphia Ch) fusion gene
BCR-ABL tyrosine kinase inhibitor
Monitor disease and therapeutic response
WBC, Neutrophils 50-500
Hypercellular BM with spectrum of immature (e.g. myelocytes) and mature
granulocytic cells in the blood
You are asked to see a 76 year old man on the wards, who presented with fatigue, dyspnoea, bleeding gums and nightsweats. His abdomen is massively enlarged. You read his notes and find ‘bone marrow aspirate: ‘dry tap’. What would you expect to see on the blood film?
Tear drop poikilocytes:
A dacrocyte (or dacryocyte) is a type of poikilocyte that is shaped like a teardrop (a“teardrop cell”). A marked increase of dacrocytes is known as “dacrocytosis”. These tear drop cells are found also in beta thalassemia major, especially after splenectomy.
erythromelalgia
Burning sensation of the hands and feet is denoted by the term
A 64-year old woman receiving long-term chemotherapy for lymphoma presents with worsening bone pain, recurrent fever and night sweats. Blood film shows blast cells with Auer Rods.
Acute myeloid leukaemia
As listed above, plus:
Lymphadenopathy less common
Quick subtype facts:
M3:Acute promyelocytic leukaemia – prone to DIC
M4+5: Monoblasts/monocytes - Skin / gum infiltration + hypokalaemia
High WCC
Auer rods and granules
Myeloperoxidase and Sudan black B stains
High WCC
Chemotherapy:
Similar principles to ALL but…
No CNS prophylaxis / maintenance
therapy needed
Consider allo-SCT in young
Specific: ATRA for M3 (acute promyelocytic leukaemia)
Supportive:
Similar principles to ALL
Prognosis worse with age
A 61-year-old man with CLL presents with recurrent pneumonia and haemoptysis. On fibreoptic bronchoscopy, the patient is found to have an endobronchial mass. The biopsy shows anaplastic, large cell lymphoma.
Richter’s syndrome is a tranformation of CLL to diffuse large B-cell lymphoma
Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
Features
often none
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than CML
Symmetrical painless lymphadenopathy
Complications
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter’s transformation)
Investigations
blood film: smudge cells (also known as smear cells)
immunophenotyping
Prognostic factors
LDH raised, CD38 +ve, 11q23 deletion = bad
Hypermutated Ig gene, Low ZAP-70 expression, 13q14 deletion = good
A newly diagnosed ALL patient complains of tiredness, polyuria, polydipsia, abdominal pain and vomiting on receiving chemotherapy. On examination, BP: 160/100mmHg, temp: 39ºC, and ECG shows tented T waves. Blood test shows serum K+: 6.9mmol/L and phosphate: 7.1 mmol/L. (hypokalemia getting out of control - potassium goes outside the cells)The patient later dies of cardiac arrest.
Tumour-lysis syndrome
Tumour lysis syndrome (TLS) is a potentially deadly condition related to the treatment of high grade lymphomas and leukaemias.
It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy.
On occasion it can occur with steroid treatment alone.
A routine medical of 33-year-old footballer reveals: Hb = 9.9g/dl and WCC = 130 x 109/L. His blood film shows whole spectrum of myeloid precursors, including a few blast cells. He admits to having frequent night sweats and blurred vision. There is a presence of Ph chromosome t(9;22) on cytogenetic analysis.
Chronic myeloid leukaemia:
A myeloproliferative disease
Middle-aged (40 to 60); median survival 3-5 years.
Often diagnosed on routine bloods (large number of differentiated neutrophils), now very
successfully treated in the majority
O/E: splenomegaly - often massive
Investigations:
Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)
PCR for BCR-ABL (Philadelphia Ch) fusion gene
Monitor disease and therapeutic response
WBC, Neutrophils 50-500
Hypercellular BM with spectrum
A 5-year-old girl presents with failure to thrive, recurrent fever and bruising. Immunotyping reveals the presence of CD10.
Acute lymphoblastic leukaemia
All clinical features listed above, plus:
Lymphadenopathy +++
CNS involvement +++
Testicular enlargement
Thymic enlargement (mediastinum)
Maintenance: 2 years in girls and adults, 3 years in boys:
Consider allo-Stem Cell Transplant
Supportive: Blood products, ABx,
Allopurinol, fluid, electrolytes – to
prevent tumour lysis syndrome
A patient has acute lymphoblastic leukaemia. A bone marrow biopsy will show infiltration by which cells?
Blast cells (lymphocyte precursors)
Patients with this inherited disorder have an increased risk of developing acute leukaemia.
Down’s syndrome
An environmental factor associated with acute leukaemia.
Ionising radiation
A 50yr old man presents to his GP complaining of weight loss, tiredness, easy bruising and a painful big toe. On examination his spleen is massively enlarged. Investigation shows a raised serum urate. The peripheral blood film is abnormal, showing proliferation of which type of cell?
Neutrophils CML. Increased mass of turning-over cells generates urate.
Investigations:
Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)
A 65yr old lady is seen in the haematology clinic where she has been treated for 7 years with Imantinib for CML. Having been previously well, she is now complaining of shortness of breath and general weakness. Examination reveals splenomegally. Her peripheral blood film has changed from previous appointments and reflects the progression of her disease. Which type of cell is now proliferating?
Blast cells CML, blast phase. Transformation tends to be into AML but in 20% is lymphoblastic (ALL). Splenomegaly is characterisitic feature
Blast Phase
>20% blasts in BM/blood
Resembles ALL; timeframe = months (+/- WL, lethargy, night sweats)
Treatment similar to AML, possibly with allogeneic SCT for young pts.
Chronic phase
<5% blasts in BM/blood, WBC slowly increases over years (indolent)
Rx = Oral hydroxyurea/interferon suppress WCC. Imatinib (BCR-ABL tyrosine kinase
inhibitor) or dasatinib/nilotinib for resistance; extremely effective. BMT potentially
curative.
Accelerated Phase
>10% blasts in BM/blood
Increasing manifestations, such as splenomegaly, lasting up to a year
Less responsive to therapy
A 70yr old man complains of a year’s history of fatigue, weight loss and recurrent sinusitis. His white cell count is raised with a lymphocytosis of 283x109 /L. Blood film shows features of haemolysis and Coomb’s test is positive. Further investigation show the bone marrow, blood and lymph nodes are infiltrated with which cell population?
Clonal B lymphocytes Only two chronic B cell leukaemia/lymphomas are CD5+: CLL (CD5+ CD23+) and Mantle Cell Lymphoma (CD5+ CD23-). CLL may be assoc. with Coombs positive AIHA and ITP. The combination is called Evans syndrome.
A routine full blood count on a 62yr old gardener reveals a high white cell count of 154x109 /L, and the differential shows this to be a neutrophilia. The haemoglobin and platelet count are normal. Biopsy shows a hypercellular “packed” bone marrow, and cells show the presence of which chromosomal abnormality?
Chromosome 9;22 translocation
Moderate anaemia, splenomegaly, bony deformity, gallstones
o β- thalassaemia intermedia
Skin pigmentation, nail dystrophy, oral leukoplakia (triad) + BM failure
Dyskeratosis Congenita
X-linked. Chromosome instability (telomere shortening)
A 60 year old female patient with the following blood results: neutrophils 0.4 x 109/l, platelets 19 x 109/l and reticulocytes 50 x109/l.
The inability of BM to produce adequate blood cells
Haemopoeitic stem cell numbers are reduced in BM trephines (hypocellular BM)=but there are no blasts, if the blasts were present this would mean it is refractory anemia with excess/low number of blasts.
AA typically refers to anaemia – i.e. just RBCs – however these patients can have a
pancytopenia as well
Symptoms/signs relate to each cytopaenia
Patients typically present with bleeding problems
Can affect any age
A 76 year old man presents to his GP with increasing tiredness, weakness and a long-standing cold. The blood results ordered by the GP showed that the gentleman was anaemic and that increased blast cells were present.
AML
Auer Rods
Blast cells (20%)
Quick subtype facts:
M3: Acute promyelocytic leukaemia – prone to DIC
Specific: ATRA for M3 (acute promyelocytic leukaemia)
M4+5: Monoblasts/monocytes - Skin / gum infiltration + hypokalaemia
An 83 year old woman presents to the A&E Departments with severe weakness and SOB (pancytopenia)
On examination, masses are felt in both left and right upper quadrants of the abdomen (hepato and splenomegaly) Blood film show leukoerythroblastic cells and teardrop poikilocytes.
A MPD where myeloproliferationfibrosis of BM or replacement with collagenous tissue
Primary (idiopathic) vs secondary following PRV, ET, leukaemia etc).
Usually elderly
Pancytopaenia-related symptoms
Extramedullary haematopoeisis - hepatomegaly, massive splenomegaly, WL, fever
Investigations
Blood film – tear-drop poikilocytes (dacrocyte), leukoerythroblasts (primitive cells)
BM – fibrosis, “dry tap”
Treatment
Support with blood products, in some cases - splenectomy
Hydroxycarbamide, thalidomide, steroids and SCT also used.
Skeletal abnormalities (radii, thumbs), renal malformations, microopthalmia, short, stature, skin pigmentation
Fanconi anaemia
Inherited AA / BM failure syndrome
Fanconi Anaemia (cf Fanconi Syndrome = renal)
Autosomal recessive. Pancytopenia
Presents at 5-10yrs
A 35 year old women complains of abdominal pain. There is associated pancytopenia, and a Ham’s test is positive.
Paroxysmal nocturnal haemoglobinuria:
Acquired loss of protective surface GPI markers on RBCs (platelets + neutrophils) → complement-mediated lysis → chronic intravascular haemolysis especially at night.
Morning haemoglobinuria, thrombosis (+Budd- Chiari syndrome – hepatic v thromb).
Diagnosis: immunophenotype shows altered GPI or Ham’s test (in vitro acid-inducedlysis).
Treatment: iron/folate supplements, prophylactic vaccines/antibiotics. Expensive
monoclonal antibodies (eculizumab) that prevents complement from binding RBCs
Features
haemolytic anaemia
red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
thrombosis e.g. Budd-Chiari syndrome
aplastic anaemia may develop in some patients
Diagnosis
flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham’s test as the gold standard investigation in PNH
Ham’s test: acid-induced haemolysis (normal red cells would not)
Management
blood product replacement
anticoagulation
eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
stem cell transplantation
A 19 year old Jewish male presenting with multiple pathological fractures and hypersplenism.
Gaucher’s disease (glucosylceramide lipidosis)
Massive splenomegaly
myelofibrosis
chronic myeloid leukaemia
visceral leishmaniasis (kala-azar)
malaria
Gaucher’s syndrome
A 26 year old primary school teacher presents with chronic anaemia. She has an increased (unconguated) bilirubin, and has had well controlled systemic lupus erythematosus for 7 years.
generally seen in young children and produces a triad of:
acute renal failure
microangiopathic haemolytic anaemia
thrombocytopenia
HUS: Haemolytic uraemic syndrome.
toxin damages endothelial cellsfibrin mesh and RBC damageimpaired renal function + microangiopathic haemolytic anaemia.
Diarrhoea, renal failure, no neuro problems, children and elderly.
- failure to thrive
- jaundice, gallstones
- splenomegaly
- aplastic crisis precipitated by parvovirus infection
- degree of haemolysis variable
- MCHC elevated
Hereditary spherocytosis
Clinical features: can be severe neonatal jaundice, splenomegaly, haemolytic anaemia
Treatment: most do not require treatment (can incl blood transfusion or splenectomy)
Pyruvate kinase deficiency
Autosomal recessive (but autosomal dominant has been observed with the disorder)
Mr RX came to Fulham from Thailand last year. He has inflammatory bowel disease and is taking dapsone for his dermatitis herpetiformis. Which of the above conditions would be likely and clinically relevant?
G6PD - dapsone
Dapsone is used to treat dermatitis herpetiformis. Dapsone is known to cause haemolysis in G6PD deficient patients, so it is avoided. G6PD deficiency in commoner in Thai people.
In which condition might a Donath-Landsteiner be positive?
Paroxysmal cold haemoglobinuria
Cold Agglutinin Disease
Features
>37oC
IgM
Positive Coombs test
Often with Raynaud’s
Causes
Lymphoma, Infections: EBV, mycoplasma
Management
Steroids
Treat underlying condition
Splenectomy
Avoid the cold
Immunosuppression
Chlorambucil (chemo)
A 49 year old female complains of abdominal pain and vomiting a few minutes after the start of transfusion. O.E she is tachycardic and has facial flushing. Urinalysis reveals haemoglobinuria.
Immediate Transfusion Reaction
ABO incompatbility
A 28 year old female presents with fever < 40 C and rigors approx. 1 ½ hours after transfusion. She has two children and previously had a blood transfusion 7 years ago.
Febrile non-hemolytic transfusion reaction
A 44 year old male develops a pyrexia of >40 C and marked hypotension very shortly after receiving a blood transfusion. He has never had a transfusion before and there is no evidence of ABO blood group / rhesus incompatibility.
Bacterial Infection of Unit
A 78 year old man is found collapsed in his bathroom at home. Tests reveal that he is anaemic and has raised urea and creatinine levels. Over the next 24 hours he receives 3 litres of fluid and a blood transfusion. He then becomes dyspnoeic. Examination reveals a raised JVP, basal crepitations and ankle oedema.
Fluid overload
An 18 year old boy with sickle cell anaemia is observed to have short stature. Further tests reveal poor cardiac function
An 18 year old boy with sickle cell anaemia is observed to have short stature. Further tests reveal poor cardiac function
In contrast, delayed haemolytic transfusion reaction (DHTR) manifests days to weeks after a transfusion, acommpanied by a falling haemoglobin and jaundice or haemoglobinuria.
A 55 year old British female developed an itchy, diffuse erythematous rash on both arms fifteen minutes after receiving a blood transfusion. This rash responded well to acrivastine.
Allergic reaction to transfusion
A 36 year old Italian gentleman presented with severe bruising across the dorsal aspect of his left arm one week post-transfusion. FBC results included: Hb = 15g/dL, platelets = 8x109/L and WBC = 5.5x109/L.
Post Transfusion Purpura
A 72 year old Australian man developed a fever and jaundice five days post-transfusion. FBC revealed Hb = 9g/dL and MCV = 105fL with haemoglobinuria noted on urine dipstick testing.
Delayed haemolytic transfusion reaction (DHTR)
Patient has a severe anaphylactic reaction soon after transfusion. Signs and symptoms include wheeze, raised pulse, low blood pressure and laryngeal oedema.
IgA deficiency
Patient develops mild symptoms of fever and rigors a few days after transfusion, with a rise pulse rate.
febrile non-hemolytic transfusion reaction
A 33 year old patient has just given birth to her second child. The baby is jaundiced and placed under a UV lamp. What investigation would you perform to test for foetal haemoglobin-containing red cells?
Kleihauer test
The Kleihauer–Betke (“KB”) test, Kleihauer–Betke (“KB”) stain, Kleihauer test or Acid elution test, is a blood testused to measure the amount of fetal hemoglobin transferred from a fetus to a mother’s bloodstream.
A Kleihauer test is used to confirm transplacental blood loss from fetus to mother. The test is performed on the mother’s blood; the blood undergoes acid elution and staining. Fetal red cells contain HbF and are therefore more resistant to acid elution than the maternal cells. The fetal cells therefore stain red, maternal cells stain pink.
A 23 year old Middle Eastern man with beta thalassaemia major complains of a bronze skin discolouration.
Iatrogenic Iron overload
A female infant presents to A&E with symptoms of hypoxia. It is noted that she has dactylitis.
sickle cell
A child is known to have a blood disorder and seems to have suffered from a stroke. What is the blood disorder that this child is most likely to have?
Sickle Cell Disease
A routine blood sample is taken from an asymptomatic neonate. Results reveal a raised Hb, a raised WCC and a raised MCV. Both Hb A and F are present.
Normal Neonate
A male infant is admitted to hospital for a routine circumcision. During the operation haemostasis seems to be impaired. His mother failed to mention in the family history that her father had some sort of blood disorder.
Haemophilia, Factor VIII
X-linked recessive affecting 1/10,000 males
o Presentation: often early in life or prolonged bleeding after surgery/trauma
o Diagnosis: ↑APTT, normal PT and ↓ factor VIII assay.
!!!!!!!Rember this - it is very important!!!!!!!!
oSeverity:relatedtofactorleveleg.
Management:AvoidNSAID and Minjections,desmopressin(vWFrelease
which is VIII carrier), factor VIII concentrates as replacement which is life long
A 6 month old girl is brought to her GP by her Greek Cypriot parents. They complain that she looks small compared to their neighbour’s baby of the same age. They also think her face looks funny. On examination, you note pallor and jaundice, the baby’s skull appears bossed and there is maxillary prominence. There is also marked hepatosplenomegaly. Her blood film shows a microcytosis and haemoglobin analysis shows high levels of HbF and HbA2.
Thalassaemia Major
A young boy is referred to you because of prolonged bleeding following circumcision. You also note some bleeding of the gums. Coagulation tests reveal a normal PT but a raised APTT and an increased Bleeding Time. Analysis of clotting factors reveals a low Factor VIII.
Von Willebrand’s Disease
Von Willebrand’s disease
o Several types – quantitative (deficiency) vs. qualitative
o ↓ platelet function and ↓ factor VIII (vWF carries factor VIII in circulation)
o Mostly AD affecting 1/10,000 -Very Important!!!!
o Presentation: often bleeding indicative of platelet disorders (i.e. mucocutaneous bleeding) but can also include bleeding indicative of coagulation disorders
o Diagnosis:
↑APTT,↑bleedingtime,↓FactorVIII,↓vWFAg.
VWF) is the carrier molecule for FVIII, preventing its premature degredation in the circulation, so if VWF is low, FVIII is vulnerable to degredation and is therefore also low.
NormalINR&plts o Management:
Desmopressin, VWF and Factor VIII concentrates
A baby with Down’s syndrome is noted, on routine blood testing, to have large numbers of circulating megakaryocyte blast cells and nucleated red blood cells. A repeat blood film 2 months later is normal.
Transient Abnormal Myelopoiesis
What is the platlet count in Haemophila and vwD?
Haemophilia and VWD have normal platelet count.
Why can G6PD levels be normal in G6PD deficiency? I
n an acute haemolytic crisis we would mount a reticulocyte response (young red cells) which have a high level of G6PD, therefore this may elevate the measured G6PD level. Therefore you would have to measure the G6PD level after the acute haemolytic episode has resolved, to see if the patient is truly G6PD deficient. ps polychromatic macrocytes = reticulocytes (polychromasia due to ribosomal RNA)
You are asked to see a neonate who while being treated for a urinary tract infection with Nitrofurantoin has developed jaundice. The blood film shows Heinz bodies, “bite cells” and polychromasia. What is the likely diagnosis?
Glucose-6-phosphate dehydrogenase deficiency
A 4 year old Afro-Caribbean girl presents to A&E with severe bony pain in her hands and feet and shortness of breath. Her oxygenation is 85% on air. On investigation her Hb is found to be very low at 6.3g/dl. What is the likely diagnosis?
B.
Sickle cell anaemia
A 2 year old girl presents to his GP following a viral illness with purpuric rash, ecchymoses and epistaxis. Normal haemoglobin and white cell count and platelets 19x109/L. Bone marrow show increased numbers of megakaryocytes (platlets precursors(. What is the likely diagnosis?
Autoimmune thrombocytopenia
Thrombocytopenia (norm plt count 150- 400x109 g/l
A 9 month old boy presents to A&E with excessive bleeding following circumcision. Laboratory investigations reveal a prolonged activated partial thromblastin time (APTT), normal prothrombin time (PT) and a factor VIII level which is 10% of normal. Bleeding time is normal. What is the likely diagnosis?
Heampophila VIII (A)
α- Thalassaemia:
Deletions - reduced α-chain synthesis, excess β-chains
*4 α genes, severity depends on number deletedo α- thalassaemia trait (1/2 deleted) →
*HbH disease (3 deleted) →
*Hydrops Foetalis (4 deleted) →
- Asymptomatic, mild anaemia
- Moderate anaemia, splenomegaly
- Incompatible with life
is a genetic disorder in which glucocerebroside accumulates in cells and certain organs.
The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher’s disease may be treated with enzyme replacement therapy.
The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females.
Gaucher’s disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD)
About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews
Free light chains produced by abnormal plasma cells that are small enough to pass into the urine.
Bence jones protein
Found in patients with Myeloma with low serum albumin and oedema.
amyloid
A monoclonal immunoglobulin which appears as a dense narrow band (M band) on electrophoresis.
Paraprotein - IgG
Stimulated by IL-6 secreted by cells in the vicinity of the myeloma cells. Produces radiological changes resembling those of generalized osteoporosis.
osteoclasts
Misfolded protein deposited in myeloma-associated amyloidosis
Amyloidosis
Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.
Can be primary or secondary:
PRIMARY (AL amyloidosis)
● Most common
● Deposition of amyloid L protein
● Most associated with plasma cell dyscrasias and with paraproteins, e.g. multiple myeloma (although most don’t have multiple myeloma)
● Most have monoclonal Ig, f_ree light chains in serum_ and urine (Bence Jones) and increased bone marrow plasma cells
A condition involving a low level of paraprotein (IgG secreted by the plasma cells) in the blood in usually asymptomatic elderly patients
MGUS: Monoclonal Gammaglobinopathy of Unknown Significance
- <10% plasma cells in marrow, <30g/l monoclonal paraprotein, no CRAB etc.
- Incidental finding; progresses to multiple myeloma at a rate of 1-2% / year
- “Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement
Induction chemotherapy regimen with the best evidence pre-autologous stem-cell transplant in multiple myeloma
Lenalidomide + low dose dexamethasone
Monoclonal immunoglobulin raised in macroglobinaemia
Waldenstrom’s Macroglobinaemia (Lymphoplasmacytoid Lymphoma - LPL)
- Elderly men
- Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness
- Lymphoplasmacytoid cells produce monoclonal serum IgM that
- infiltrates the LNs/BM
Treatment: plasmapheresis for hyperviscosity; chlorambucil,
cyclophosphamide and other chemo
Factor(s) associated with a very poor prognosis in multiple myeloma
Anaemia & renal failure
Proteasome inhibitor active in myeloma
Bortezomib
Asymptomatic, serum monoclonal protein 25g/L, marrow plasma cells 5% (<10%), serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal- normal kidney function
Elderly men
Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF
A low-grade NHL; lymphoplasmacytoid cells produce monoclonal serum IgM that infiltrates the LNs/BMmuscle weakness)
Treatment: plasmapheresis for hyperviscosity; chlorambucil,
cyclophosphamide and other chemo
Waldenstrom’s Macroglobinaemia (IgM)
Aβ amyloid
Asymptomatic, serum monoclonal protein 30g/L, marrow plasma cells 10%, serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal
Smouldering multiple myeloma
“Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement
No Rx required for both at this stage. Monitor for transformation.
Asymptomatic, serum monoclonal protein 10g/L, marrow plasma cells 15%, serum Ca 2.3 mmol/L, estimated GFR 30 mL/min, Hb 8 g/dL, lytic vertebral lesions
Multiple myeloma
Abdo pain, serum monoclonal protein 10g/L, marrow plasma cells >10%, serum Ca 2.6 mmol/L, estimated GFR 30 mL/min, Hb 8 g/dL, lytic vertebral lesions
.
Multiple myeloma
Previously fit 35yo Afro Carribean female, sudden onset back pain, no history of trauma, 1 month history polyuria, urine specific gravity raised but dipstick negative for protein (and normal in all other respects), estimated GFR 70mL/min, vertebral fracture and bilateral femoral neck fractures on radiograph.
CRAB
- young
- African
- fracture
- urine specific gtavity raised
- decreased GFR
Which paraprotein is most commonly raised in patients with multiple myeloma?
IgG
Which cytokine is an important growth factor in the development of myeloma?
IL-6
Free light chains that are small enough to pass into the urine.
Bence-Jones protein
Elevated levels imply a poor prognosis in myeloma patients.
Beta2 microglobulin and albumin levels to stage a patient’s disease into one of three stages. The only other factor that has been shown to impact significantly on outcome is age (and cytogenetics to some extent).
Condition usually in asymptomatic elderly patients with a low level of paraprotein in the blood.
Monoclonal gammopathy of undetermined significance (MGUS)
A 52 yr old woman who has a 5 yr history of rheumatoid arthritis and has recently been found to have proteinuria. Further examination revealed hepatosplenomegaly.
A rectal biopsy stained with Congo Red showed apple green birefringence in polarised light.
it is secondary as it is due to inflammatory conditions.
A 60 yr old woman presents to her GP with fatigue and bone pain. Examination of her bone marrow demonstrated >10 % plasma cells, and a monoclonal protein in the serum (IgG) . Further investigations showed a hypercalcaemia (CRAB)
Multiple Myloma
A 65 yr old man presents to his GP with general malaise, weight loss and visual disturbances that he likens to looking through a watery car windscreen. On examination he has peripheral lymph node enlargement. Protein electrophoresis shows an IgM paraprotein.
Elderly men
A low-grade NHL; lymphoplasmacytoid cells** produce **monoclonal serum IgM that infiltrates the LNs/BM
Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness)
Treatment: plasmapheresis for hyperviscosity; chlorambucil,
cyclophosphamide and other chemo
A 73 yr old man is shown to have paraprotein in blood <2g/L. Further investigations reveal no renal impairment or bone destruction.
Monoclonal gammopathy of undetermined significance
(MGUS)
No Rx required for both at this stage. Monitor for transformation.
MGUS: Monoclonal Gammaglobinopathy of Unknown Significance
<10% plasma cells in marrow, <30g/l monoclonal paraprotein, no CRAB etc.
Incidental finding; progresses to multiple myeloma at a rate of 1-2% / year
“Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement
A 60 yr old woman presents to her GP with shortness of breath and ankle oedema. When examined the patient has bilateral weakness and paraesthesia of her hands.
Investigations revealed a monoclonal proliferation of plasma cells and the presence of Bence Jones proteins.
Amyloidosis
Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.
Can be primary or secondary:
PRIMARY (AL amyloidosis)
● Most common
● Deposition of amyloid L protein
● Most associated with plasma cell dyscrasias and with paraproteins, e.g. multiple myeloma (although most don’t have multiple myeloma)
● Most have monoclonal Ig, free light chains in serum and urine (Bence Jones) and increased bone marrow plasma cells
Clinical features: caused by amyloid deposits in various organs:
(1) KIDNEY: nephrotic syndrome = most common presentation
(2) HEART: conduction defects, heart failure, cardiomegaly
(3) LIVER/SPLEEN: hepatosplenomegaly
(4) TONGUE: macroglossia in 10%
(5) NEUROPATHIES: including carpal tunnel
A 49-year-old woman presented with a 6-month history of vague aches and pains in her chest. On examination, she was overweight but had no abnormal physical signs. Protein electrophoresis showed a small paraprotein band in the gamma region; this band was an IgG of lambda type. A bone marrow biopsy showed only 12% plasma cells. There was no protein in her urine.
Benign paraproteinaemia
A 71-year-old man presented with sharp, constant, low back pain, dating from a fall from a ladder 6 weeks earlier. He admitted to vague malaise for over 8 months. He had a raised serum calcium level (3.2mmol/l) but a normal alkaline phosphatase.
X-rays of his back showed a small, punched-out lesion in the second lumbar vertebra and
a Bone marrow biopsy showed an increased number of atypical plasma cells; these constituted 45% of the nucleated cells found on the film.
Multiple Myloma
A 43 year old man presents to his GP with concerns over a tender lump on the left side of his abdomen. Investigation showed a normal haemoglobin but a mildly raised white-cell count (13.2 x 109/l). On the blood film these cells were mainly small mononuclear cells resembling lymphocytes. These cells stained positively for tartrate-resistant acid phosphatase.
Hairy Cell Lukemia - a subtype of CLL
A 78 year old man is admitted to hospital after experiencing problems urinating and defecating. He also noticed numbness in some areas of his abdomen. Blood levels of calcium and ALP were raised. A bone scan confirms the diagnosis.
Bone metastasis
A 69 year old man presents with a complaint of right elbow pain. Radiography shows a lytic lesion in the area of the right proximal radius.
Biopsy of the lesion reveals a mono-clonal population of plasma cells consistent with a plasmacytoma.
A radiographic skeletal bone survey shows other similar lesions.
MM
Corticosteroid refractory haemolytic anaemia
Splenectomy
Chronic lymphocytic leukaemia managment
Cyclophosphamide, fludarabine and rituximab
Chronic myeloid leukaemia (also known as chronic granulocytic leukaemia) treatment
Imatinib
Polycythaemia rubra vera
Venesection and aspirin
Multiple myeloma managment
Lenalidomide (Revlimid)
and low dose dexamethasone
followed by autologous stem cell transplant (SCT)
Smouldering myeloma
Regular surveillance but no active treatment
MGUS
Regular surveillance but no active treatment
DiGeorge children are ineligible for this operation.
Thymectomy
Used in solid organ transplantation, multiple sclerosis, NHL. Depletes lymphocytes. Side effects include ITP and Graves disease.
Campath (anti CD52, alemtuzumab)
Anti-proliferative used in polycythaemia rubra vera and essential thrombocythaemia
Hydroxyurea
Reduces platelet count in thrombocythaemia but causes palpitations, tachycardia, fluid retention
Anagrelide
Standard prophylaxis accompanying a once weekly myelosuppressant when used in rheumatoid arthritis
Folate
Rescue drug after high dose methotrexate is used for gestational trophoblastic disease or intrathecal ALL
Leucovorin (Folinic acid, Formyl tetrahydrofolate)
Used in solid organ transplantation, multiple sclerosis, NHL. Depletes B lymphocytes more than T lymphocytes.
Rituximab (anti CD20)
Add-on anti-proteasome drug for myeloma
Bortezomib (Velcade)
Anti-proliferative used in PRV and essential thrombocythaemia
Hydroxyurea
Reduces platelet count in thrombocythaemia but causes palpitations, tachycardia, fluid retention
Anagrelide
Standard prophylaxis accompanying a once weekly myelosuppressant when used in rheumatoid arthritis
Folate
Rescue drug after high dose methotrexate is used for gestational trophoblastic disease or intrathecal ALL
Leucovorin (Folinic acid, Formyl tetrahydrofolate)
Used in solid organ transplantation, multiple sclerosis, NHL. Depletes B lymphocytes more than T lymphocytes.
Rituximab (anti CD20)
case 4:
A 60 year old man with WCC 35x109/L and a peripheral blood film shows that these are lymphocytes.
Immunophenotype:
CD 19 + CD20 + CD10 - CD3 -
CD4 - CD5 + Kappa 2% Lambda 96%
Could someone please explain why this is B cell malignancy not T cell malignancy given that both B and T cell markers are present? I think the lecturer explained that but I didn’t catch that….
However in some malignant B cell development the malignant cells continue to aberrantly express CD5 as part of the disorganised malignant phenotype So short answer here is if you see a high lymphocyte count marking as B cells but aberrantly expressing CD5 think Chronic lymphocytic leukaemia. CLL prognostic factors are many but important ones are Immungolobulin gene configuration (mutated or unmutated) Zap 70 expression Cytogenetics (trisomy 12, del 13q or 17p
Myeloma
Variable B cell
Burkitts Lymphoma
Aggressive B cell
ATLL
Aggressive T cell
Most easily curable B cell neoplasm
Aggressive B cell
Follicular lymphoma
Indolent B cell
A 25 year old man presents with a single enlarged painless cervical lymph node (I) and complains of drenching night sweats (B symptoms) Histology shows the presence of Reed-Sternberg cells.
Hodgkins Disease Stage IB
An elderly lady is found to suffer from EBV virus. She is late noted to have splenic enlargement.
Burkitt’s Lymphoma
During an insurance medical a 32 year old IT consultant was found to have hilar lymphadenopathy on his chest x-ray.
He also complains of a painless lump under his right arm.
Hodgkins Stage IIA
Advanced Hodgkins disease should be treated with…..
Combination Chemotherapy
Pathological stage IA or IIA disease may be treated with……
ABVD combination chemotherapy + radiotherapy if required
A subtype of Non-Hodgkin lymphoma associated with very aggressive disease.
Burkitt’s Lymphoma
A classical but rare constitutional symptom of Hodgkin lymphoma.
Pel Ebstein Fever
The stage characterised by multiple lymph node involvement 2 on the same side of the diaphragm but without constitutional symptoms A
2A
The grade of the Follicular lymphoma NHL subtype.
Indolent
A patient presents with a lump in his groin and complains of night sweats and an itchy rash.
A biopsy is taken and on inspection is shown to include Reed-Sternberg cells.
Hodgkin lymphoma
A 61 year old lady complains to her GP of morning stiffness and aching in her hips. She also suffers from anorexia, fatigue and occasional night sweats. She is found to have a raised ESR. Of note she has had giant cell arterititis in the past.
What is the most likely diagnosis from the list above.
Polymalagia Rheumatica
An 81 year old man with known prostatic carcinoma presents to his GP with severe bone pain. Blood tests reveal a mild anaemia and peripheral blood film shows nucleated red blood cells and immature myeloid cells. What are these haematological features collectively known as?
Leucoerythroblastic anaemia
A 51 year old man is having work up for palliative surgery due to gastric adenocarcinoma.
He is found to be anaemic, with high a reticulocyte count and fragmented red blood cells on blood smear.
What is this anaemia known as?
A 21 year old student recently returning from India complains to his GP of cough, headache and diarrhoea. He is febrile and rose spots are present on his chest. Blood culture reveals salmonella typhi. Which immune cells out of the list are most likely to be raised?
Monocytes
Anaemia and neutropenia are more common in which of the above autoimmune disease?
Systemic lupus erythematosis
A peripheral blood smear of a thrombocytopenic patient raised Lactate dehydrogenase and unconjugated bilirubin shows fragmented Red blood cells.
A markedly raised Hg in a patient with renal cell carcinoma.
Secondary true polycythaemia
Monocytosis but with a normal neutrophil count.
Brucella infection
A markedly raised haemoglobin in a patient with splenomegaly
Polycythaemia vera
is an inherited condition which results in X being resistant to degradation by activated Protein C; this predisposes affected individuals to development of clots.
Factor V Leiden
A peripheral blood smear of a thrombocytopenic patient raised Lactate dehydrogenase and unconjugated bilirubin shows fragmented Red blood cells.
Microangiopathic haemolytic anaemia
A markedly raised haemoglobin in a patient with renal cell carcinoma.
Secondary true polycythaemia
Monocytosis but with a normal neutrophil count.
Brucella infection
A markedly raised haemoglobin in a patient with splenomegaly
Polycythemia Rubra Vera
Neutrophilia with visible toxic granulation and vacuoles on the blood film. The monocyte count is normal.
Acute fungal infection
A patient with a positive coombs test and a blood film showing spherocytes.
A 30 year old female presents to her GP complaining of aches and pains in her joints and a rash on her face after returning from a holiday in Spain.
Her blood tests show a normocytic anaemia, an elevated ESR and a positive Anti-Nuclear Antibodies test.
SLE
A 22 year old female who has recently undergone surgery presents with difficulties breathing and swelling of the face, hands and feet. She also complains of severe abdominal pains. She has experienced similar problems in the past.
Hereditary angioedema
Hereditary angioedema is an AD condition associated with low plasma levels of the C1 inhibitor (C1-INH) protein.
C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.
Investigation
C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool
Symptoms
- attacks may be proceeded by painful macular rash
- painless, non-pruritic swelling of subcutaneous/submucosal tissues
- may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
- urticaria is not usually a feature
Management
- acute: IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
- prophylaxis: anabolic steroid Danazol may help
A 16 year old male is rushed into A+E with severe SOB and wheezing.
He is also noted to have urticaria and he is tachycardic and hypotensive with decreasing consciousness.
Anaphylaxis
antibodies Sjorgen
Anti-Ro, Anti-La antibody (speckled pattern), 60-70% have positive RF
scleroderma antibodies
A 25 year old man presents with a single enlarged painless cervical lymph node (I)and complains of drenching night sweats (B). Histology shows the presence of Reed-Sternberg cells.
Hodkin stage IB
An elderly lady is found to suffer from Epstein-Barr virus. She is late noted to have splenic enlargement.
During an insurance medical a 32 year old IT consultant was found to have hilar lymphadenopathy on his chest x-ray. He also complains of a painless lump under his right arm.
Hodgkins Stage IIA
Advanced Hodgkins disease should be treated with…..
Combination Chemotherapy
Pathological stage IA or IIA disease may be treated with……
Radiation Therapy Alone
