Haematology Flashcards
1
Q
Describe Amyloidosis and its types, and features,
A
A group of disorders characterised by extracellular deposition of a protein in abnormal fibrillar form. Can be primary (AL amyloid “L for immunoglobulin Light chain fragment”) or Secondary (AA amyloid “A for precursor serum amyloid A protein”) or familial.
AL Amyloid (primary) features: associated with waldenstroms and lymphoma. Kidneys: nephrotic syndrome Heart: restrictive cardiomyopathy (looks sparkling on echo), arrhythmias, angina Nerves: peripheral and autonomic neuropathy, carpel tunnel syndrome Gut: macroglossia, malabsoprtion, weight loss, hepatomegaly, perforation, haemorrhage, obstruction Vascular: purpura, especially perioribtal (characteristic feature)
AA Amyloid (Secondary): RA, IBD, Chronic infections e.g. TB, Bronchiectasis. Mostly affects kidneys liver and spleen presenting with nephrotic syndrome or hepatosplenomegaly, macroglossia is not seen and rarely affects the heart.
Diagnosis is made with abdominal fat or rectal biopsy and postive Congo Red staining with red-green birefringence under polarised light microscopy.
2
Q
llWhat are Bence Jones proteins
A
Ig light chains excreted by kidney in excess in some patients with myeloma.
3
Q
What are the causes of macrocytic anaemias?
A
Megaloblastic causes: Folate deficiency, B12 deficiency, anti-folate drugs e.g (phenytoin)
Normoblastic causes: alcohol, liver disease, hypothyroidism, pregnancy, reticulocytosis, myelodysplasia, cytotoxic drugs,
4
Q
What are the causes of microcytic anaemias?
A
- iron deficiency anaemia (most common)
- thalassaemia
- sideroblastic anaemia (very rare)
- Hereditary Spherocytosis
5
Q
What are some causes of a normocytic anaemia?
A
acute blood loss anaemia of chronic disease renal failure bone marrow failure hypothyroidism (may be macrocytic) Haemolysis ( may be macrocytic) pregnancy
6
Q
Describe iron-deficiency anaemia, it’s causes, diagnostic tests and treatment
A
Commonest cause of anaemia with microcytic hypochromic RBC’s
Causes: •blood loss e.g menorrhagia or GI bleeding •poor diet •malabsorption • hookworm in tropics
Signs: conjunctival pallor, lethargy, koilonychia, atrophic glossitis, angular cheilosis
Tests: FBC shows decreased MCV, MCH and ferritin (confirms diagnosis)
Treatment: ferrous sulphate 200mg BD PO follow up FBC if no response consider sideroblastic anaemia if Hb improves but MCV still low consider thalassaemia
7
Q
What are the Side effects of oral ferrous sulphate?
A
- nausea
- abdominal discomfort
- diarrhoea or constipation
- black stools
8
Q
Describe anaemia of chronic disease (secondary anaemia)
A
2nd most common anaemia after IDA most common anaemia in inpatients Due to 3 problems:
- poor use of iron in erythropoiesis
- cytokine-induced shortening of RBC survival
- decreased production of and response to erythropoietin
tests: FBC shows normocytic anaemia with normal or raises ferritin.
9
Q
With regards to a peripheral blood film what is anisocytosis?
A
Variation in RBC size e.g. Due to megaloblastic anaemia, IDA, thalassaemia
10
Q
With regards to a peripheral blood film what are acanthocytes?
A
Acanthocytes are spiked RBCs seen in splenectomy, alcoholic liver disease, abetalipoproteinaemia, spherocytosis
11
Q
With regards to a peripheral blood film, what is basophilic RBC stippling?
A
Speckled RBC cells due to denatured RNA fragments found in RBCs indicative of accelerated erythropoiesis or defective Hb synthesis.
Causes: lead poisoning, megaloblastic anaemia, myelodysplasia, liver disease, haemoglobinopathy e.g. Thalassaemia
12
Q
With regards to a peripheral blood film, what are Burr cells?
A
RBC projections less prominent that acanthocytes may be indicative of renal or live failure or due to an EDTA storage artefact
13
Q
What are the normal values of a FBC?
A
HB: Men;130-180g/L Women;115-160g/L
MCV: 77-95fL
MCH: 27-32pg
PLT: 150-400x10^9/L
RBC: Men;4.5-6.5 Women; 3.8-5.8 x10^12/L
WBC: Men;3.7-9.5 Women;3.9-11.1x10^9/L
NEUT: Men;1.7-6.1 Women;1.7-7.5x10^9/L LYMP: 1-3.2x10^9/L MONO: 0.2-0.6x10^9/L EOS: 0.03-0.06x10^9/L BASO: 0.02-0.09x10^9/L
14
Q
What at some causes of neutrophilia and what’s is the normal range?
A
Normal range: 1.7-6.1 or 7.5 (Female) x10^9/L
Causes:
- bacterial infections
- inflammation (MI, PAN, SLE, RA etc)
- myeloproliferative disorders
- drugs (steroids)
- disseminated malignancy (e.g .colonic cancer)
- stress e.g. Trauma, surgery, burns, haemorrhage, seizure
15
Q
What are the causes of thrombocytosis?
A
Causes of increased platelets:
- bleeding
- infection
- chronic inflammation
- malignancy
- trauma
- post-surgery
- IDA
16
Q
Describe myeloproliferative disorders
A
Causes by proliferation of a clone of haemopoetic myeloid stem cells in the marrow.
Classified depending on the cell type which is proliferating:
RBC - polycythaemia rubra Vera
WBC - chronic myeloid leukaemia
PLT - essential thrombocythaemia
Fibroblasts - myelofibrosis
17
Q
What are some causes of thrombocytopenia?
A
May be due to decreased marrow production:
- aplastic anaemia
- megaloblastic anaemia
- marrow infiltration (e.g. Myeloma, leukaemia)
- marrow suppression (cytotoxics, radiotherapy)
Or may be due to excess destruction of platelets:
- immune causese e.g. ITP, SLE, CLL
- Non-immune causes: TTP or HUS, DIC, hypersplenism
18
Q
Describe Immune/Idiopathic Thrombocytopenic Purpura (ITP), its symptoms, tests, and management.
A
Caused by anti-platelet antibodies, may be acute (commonly self-limiting disease in children ~2 weeks post infection) or chronic (seen mainly in young/middle-aged women).
Symptoms:
- Acute ITP presents wth bruising, purpura, petechiae. Usually history of recent gastroenteritis or URTI.
- Chronic ITP presents with varying history of bleeding, purpura, epistaxis, menhorragia.
Tests: bone marrow biopsy shows increased megakaryocytes and anti platelet antibodies
Treatment:
- none if mild, gradual resolution over 3 months.
- if symptomatic or platelets less than 20, immunosuppression to keep platelets above 30 e.g Prednisolone 1mg/kg/d
- if no response or relapse splenectomy cures
19
Q
Describe Disseminated Intravascular Coagulation (DIC), it’s causes, investigations, and management.
A
Widespread activation of coagulation leading to consumption of clotting factors and platelets with increased risk of bleeding. Fibrin strands fill small vessels Haemolysing RBCs.
Causes: malignancy, sepsis, trauma, obstetric events, liver disease
Investigations:
- Prolonged clotting times
- Thrombocytopaenia
- Decreased fibrinogen
- Increased fibrinogen degradation products.
Treatment:
- replace platelets if less than 50, cryoprecipitate to replace fibrinogen, FFP to replace coagulation factors.
- Activated protein C reduces mortality in DIC with severe sepsis or multi-organ failure.
20
Q
What do the presence of blast cells indicate?
A
Blasts cells are nucleated precursor cells that are not normally in peripheral blood. They may be seen in myelofibrosis, leukaemia, and malignant infiltration by carcinoma
21
Q
Describe MyeloDysplastic Syndrome (MDS), its features, and management.
A
A heterogenous group of disorders that manifest as marrow failure with risk of life-threatening infection and bleeding.
May be primary or secondary due to chemotherapy or radiotherapy. 30% transform to acute myeloid leukaemia.
Features: Anaemia, Neutropenia, Thrombocytopaenia. Splenomegaly. Dysplastic cells in bone marrow biopsy
Management:
- Supportive - transfusions
- Azacytidine
22
Q
What are the main types of Leukaemia?
A
Leukaemia divides into 4 main types depending on the cell line involved.
Lymphoid:
- Acute Lymphoblastic Leukaemia (ALL)
- Chronic Lymphocytic Leukaemia (CLL)
Myeloid:
- Acute Myeloid Leukaemia (AML)
- Chronic Myeloid Leukaemia (CML)
23
Q
Describe tumour lysis syndrome, its risk factors and preventative measures.
A
Caused by a massive destruction of cells leading to release of K+, Urate, and then kidney injury.
Increased risk if levels of LDH are increased, Creatinine increased, urate increased or WCC >25
Prevention with high fluid intake and allopurinol pre-cytotoxics
24
Q
Describe Acute Lymphoblastic Leukaemia, its features, and prognostic factors.
A
A malignancy of lymphoid cells, affecting B or T lymphocyte cell lines. Commonest cancer of childhood (80%) peak age 2-5yrs, rare in adults.
Features: arise from marrow failure and organ infiltration with organomegaly, Anaemia, infection, and bleeding.
Good prognostic factors:
- French-American-British (FAB) L1 type
- Common ALL
- Pre-B phenotype
- Low initial WBC
- Del(9p)
Poor prognostic factors:
- FAB L3 type
- T or B cell surface markers
- Philadelphia translocation t(9:22)
- Age less than 2 or over 10
- Male sex
- CNS involvement
- High initial WBC over 100
- non-caucasian
25
Describe Acute Myeloid Leukeamia, its features, prognostic features, and investigations.
May occur as primary disease or following secondary transformation of a myelodysplastic or myeloproliferative disorders. Most frequently occurs in 65-75yrs but occurs at all ages.
Features: Fatigue, SOB, Bruising, Bleeding, Increased risk of infections. Weight loss.
Good prognostic features:
- T(15;17) (Acute Promyelocytic leukaemia)
- T(8;21)
Poor Prognostic features:
- Over 60yrs
- over 20% blasts after first course of chemo
- Cytogenetics deletions of chromosome 5 or 7
- pre-exsiting myelodysplastic or myeloproliferative disorder
- Treatment-related AML.
Investigations:
- May have leukocytosis with blast cells, also can present with isolated thrombocytopenia, or anaemia or even leukopenia (if extensive bone marrow infiltration)
- blast cells may be few in peripheral blood and so diagnosis depends on bone marrow biopsy. Microscopy can allow differentiation from ALL.
- Blood film may show Auer Rods
26
Describe Chronic Myeloid Leukaemia, its features, investigations, and management.
Characterised by an uncontrolled clonal proliferation of myeloid cells. It accounts for 15% of leukaemias. It is a myeloproliferative disorder. Occurs most often between 40-60yrs.
Features: Massive splenomegaly, weight loss, night sweats, malaise, infections, anaemia.
Tests: Often WBC >100 with whole spectrum of myeloid cells affected i.e. neutrophilsm myelocytes, basophils, eosinophils.
Philadelphia chromosome in 95% (a reciprocal translocation of long arms of 9 + 22, which forms BCR-ABL fusion gene on chromosome 22 which has excess tyrosine kinase activity)
Management:
- Imatinib inhibits the BCR-ABL tyrosine kinase protein and induces apoptosis in Philadelphia chromosome +ve patients.
- interferon-alpha, hydroxyurea
- Allogenic bone marrow transplant
27
Describe Chronic Lymphocytic Leukaemia, its features, prognostic factors, indications for treatment, management and complications.
Accumulation of mature B cells that have escaped programmed cell death, it is the commonest leukaemia.
Features:
- Asymptomatic
- constitutional e.g. anorexia, weight loss
- bleeding and infections
- lymphadenopathy more marked than CML.
Poor Prognostic Factors:
- male sex
- age over 70
- lymphocyte count over 50
- Prolymphocytes comprising more than 10% of WBCs
- lymphocyte doubling time less than 12 months
- Raised LDH
- CD38 expression +ve
- deletions of part of the short arm of chromosome 17 (seen in around 5-10%)
Good prognostic factor:
-deletion of the long arm of chromosome 13 is the most common genetic abnormality, being seen in around 50% of patients.
Indications for treatment:
- Progressive marrow failure i.e the development or worsening of anaemia and or thrombocytopaenia
- Massive (over 10cm) or progressive lymphadenopathy
- Massive (over 6 cm) or progressive splenomegaly
- Progressive lymphocyctosis i.e. increase of 50% over 2 months or lymphocyte doubling time of less than 6 months
- Systemic symptoms e.g. weight loss over 10%BW in previous 6 months, pyrexia for over 2 weeks, extreme fatigue, night sweats.
Management:
- Patients who have no indications for treatment are monitored with regular blood counts
- Fludarabine, Cyclophosphamide and rituximab (FCR) has now emerged as the initial treatment of choice for the majority of patients.
Complications:
- Hypogammaglobulinaemia leading to recurrent infections
- Warm autoimmune haemolytic anaemic seen in 10-15% of patients
- Transformation to high-grade lymphoma (Richter's transformation)
28
Describe Sepsis (+/-Neutropenia), the sepsis six, and severe sepsis signs.
is a potentially fatal complication of anti-cancer treatment (particularly chemotherapy). Identify with Quick Sepsis Related Organ Failure Assessment (qSOFA) with 2 or more of the following.
- SBP less than 100mmHg
- RR >22
- new altered mental state.
Do the sepsis six:
- high-flow oxygen
- IV antibiotics
- IV Fluid challange (hartmann's)
- Catheter and UO monitoring
- Serum lactate
- Blood cultures
Regularly screen for signs of severe sepsis:
- SBP less than 90mmHg
- SpO2 less than 90% despite high flow oxygen
- INR >1.5 or APTT >60s
- Plt less than 100
- UO less than 0.5ml/kg/hr
- lactate >2.0mmol/L
29
What is GCSF?
Granulocyte-colony stimulating factor is a protein that stimulats the bone marrow to make WBCs
30
Describe lymphoma
Disorders caused by malignant proliferation of lymphocytes , which accumulate in the lymph nodes causing lymphadenopathy, but may also be found in peripheral blood or infiltrate organs. They are histologically classified into Hodgkins and Non-hodgkins depending on the presence of characteristic cells with mirror-image nuclei called Reed-Sternberg cells.
31
What is the management of a high INR, in the context of a patient on warfarin with major bleeding?
- Stop Warfarin
- IV Vitamin K 5mg
- Prothrombin complex concentrate (FFP if unavailable)
32
What is the management of a high INR, in the context of a patient on warfarin with minor bleeding and INR > 8.0?
- Stop warfarin
- Give intravenous vitamin K 1-3mg
- Repeat dose of vitamin K if INR still too high after 24 hours
- Restart warfarin when INR less than 5
33
What is the management of a high INR, in the context of a patient on warfarin with no bleeding and INR > 8.0?
- Stop warfarin
- Give vitamin K 1-5mg by mouth, using the intravenous preparation orally
- Repeat dose of vitamin K if INR still too high after 24 hours
- Restart when INR less than 5
34
What is the management of a high INR, in the context of a patient on warfarin with minor bleeding and INR 5.0-8.0?
- Stop warfarin
- Give intravenous vitamin K 1-3mg
- Restart when INR less than 5
35
What is the management of a high INR, in the context of a patient on warfarin with no bleeding and INR 5.0-8.0?
- Withhold 1 or 2 doses of warfarin
| - Reduce subsequent maintenance dose
36
Describe Haemophilia A its presentation and tests, and management
Factor VIII defiency (x linked recessive) though high rate of new mutations so may be no family history.
Presentation depends on severity but is often early in life or after surgery/trauma with bleeds into joints leading arthropathy and bleeding into muscles causing haematomas (increased pressure can lead to nerve palsies and compartment syndrome)
Tests: increased APTT, decreased factor VII
Management:
- Factor VIII replacement
- 10% develop Factor VIII inhibitors
37
Describe Haemophilia B
Factor IX deficiency also know as Christmas disease, inherited x-linked recessive behaves clinically like haemophilia A
38
Describe Von Willebrand disease, the types, investigation, and management
The most common inherited bleeding disorder. Mostly in autosomal dominant fashion due mutations in vWF gene on chromosome 12. Behaves like platelet disorder i.e. epistaxis, and menorrhagia. Von Willebrand factor (vWF) has 3 roles in clotting:
- To bring platelets into contact with exposed subendothelium
- to make platelets bind to each other
- to bind to factor VIII, protecting it from destruction in the circulation
Types: (Over 20 types)
- Type 1: Partial reduction in vWF (80% of patients)
- Type 2: Abnormal form of vWF
- Type 3: Total lack of vWF (Autosomal recessive)
Investigations:
- Prolonged bleeding time
- APTT prolonged
- Reduced Factor VIII levels
- Defective platelet aggregation with ristocetin
Management:
- Tranexamic acid for mild bleeding
- Desmopression raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells.
- Factor VIII concentrate.
39
What are the causes of thrombophilia?
Thrombophilia is an inherited or acquired coagulopathy predisposing to thrombosis usually venous: DVT, PE
Inherited causes:
- factor V Leiden increase
- prothrombin increase
- protein C and S deficiency
- anti-thrombin deficiency
Acquired causes:
- Pill/HRT
- antiphospholipid syndrome
40
Describe Glucose-6-phosphate dehydrogenase (G6PD) deficiency and it's presentation.
X-linked RBC enzyme defect. Mostly affecting males in the Mediterranean, Africa and Middle/Far East. Mostly asymptomatic, but may get oxidative crises due to decreased glutathione production.
Presentation: Rapid anaemia and jaundice, precipitated by drugs (primaquine, aspirin, sulphonamides, quinolones, nitrofurantoin, NSAIDs), broad beans, or illness.
41
Describe B-Thalassemia and its treatment.
Usually caused by point mutations in the B-globin genes on chromosome 11 leading to decreased production or its absence. Can be split into Thalassemia minor/trait, intermedia and major.
Minor and intermedia do not require transfusions but may be anaemic. healthy diet fitness and folate supplements help.
Thalassemia Major require regular blood transfusions and usually presents in 1st year of life. with extramedullary haemopoiesis causing characteristic skull bossing. Also require iron-chelators to prevent iron overload.
42
What are the available anti-coagulants and which are used therapeutically and prophylactically
Prophylactic: Most commonly used is LMWH e.g. dalteparin, enoxaparin, tinzaparin. It inactivates Factor Xa It has longer half-life than heparin and response is more predictable meaning it needs only be taken once or twice daily and no monitoring is usually required.
Therapeutic: First line is LMWH and depending on cause warfarin is given in combination. LMWH is continued until INR >2.2 and until day 5 as warfarin has an initial prothrombotic effect.
43
Describe paraproteinaemia and the different types
Presence in the circulation of immunoglobulins produced by a single clone of plasma cells. There are six major categories:
- Multiple myeloma
- Waldenstroms macroglobulinaemia
- Primary Amyloidosis
- Monoclonal gammopathy of uncertain significance
- paraproteinemia in lymphoma or leukaemia (seen in 5% CLL)
- Heavy chain disease
44
Describe Sickle-cell anaemia, it's crises' and management
Autosomal recessive disorder causing production of abnormal beta-globin chains due to an amino acid substitution of glutamate to valine. Heterozygotes have sickle cell trait which is protective against malaria as cells sickle when deoxygenated and only presents an issue in severe hypoxia
Features:
-Haemolysis and chronic anaemia is usually well tolerated
-Vaso-occluive 'painful' crises common due to microvascular occlusion. Often affects marrow causing severe pain but can happen in gut (mesenteric ischaemia) CNS (stroke, seizures) or limbs (ulcers, avascular necrosis, dactylitis)
-aplastic crisis, this is due to parvovirus B19 with sudden reduction in marrow production, usually self-limiting.
-sequestration crises, mainly affects chilren as the spleen has not yet undergone atrophy. There is pooling of blood in the spleen +/- liver with organomegaly severe anaemia and shock
-Acute chest syndrome, Pulmonary infiltrates involving complete lung segments causing pain, fever, tachypnoea, wheeze and cough. A sickle crises. Prodromal painful crises occur 2.5days before any abnormalities on CXR. Chief Causes are fat embolism or infection e.g with chlamydia or mycoplasma or viruses
Management:
- oxygen if desaturating
- analgesia e.g. Morphine
- rehydration with IV fluids
- transfusion for severe anaemia
- hydroxycarbamide for anaemia ( Increase foetal haemoglobin)
45
Describe myeloma, its symptoms, tests and diagnosis.
Myeloma is a type of plasma cell dyscrasia (PCD). Plasma cell dyscrasias are due to an abnormal proliferation foa signl clone of plasma or lymphoplasmacytic cells leading to secretion of immunglobulin ultimately leading to dysfunction of many organs. Bence-Jones proteins present in 2/3 of urine. Most commonly occurs over 60 average age at diagnosis is 70
Symptoms + Signs:
- Osteolytic bone lesions (backache)
- Hypercalcaemia
- Anaemia, Neutropenia or thrombocytopenia (marrow infiltration)
- recurrent bacterial infections
- renal impairment (due to light chain deposition)
Tests:
FBC, U+E, serum and urine electrophoresis. Xrays in case of bony pain shows punched out lesions, vertebral collapse. osteoporosis. Marrow biopsy.
Diagnosis depends on:
- monoclononal protein band in serum or urine electrophoresis
- increased plasma cells on marrow biopsy
- evidence of end organ damage e.g. hypercalcaemia, renal insufficiency, anaemia.
- bony lesions.
46
What are the causes of pancytopenia?
Pancytopenia is a reduction in all the major cell lines: red cells, white cells and platelets. Causes are due to:
- Decreased marrow production i.e aplastic anaemia, infiltration (e.g. acute leukaemia, myelodysplasia, myeloma, lymphoma, solid tumours, TB) megaloblastic anaemia, paroxysmal nocturnal haemoglobinuria, myelofibrosis, SLE
- peripheral destruction: hypersplenisn.
47
Describe Aplastic anaemia, its symptoms, causes and management.
it is a rare stem cell disorder leading to pancytopenia and hypoplastic marrow.
Symptoms:Presents with features of anaemia, infection or bleeding.
Causes:Most cases are due to autoimmune, triggered by drugs or radiotherapy.
Management:
- Bone marrow biopsy needed for diagnosis,
- treatment is supportive in milder cases otherwise bone marrow transplant may be needed.
48
Describe heavy chain disease in the context of paraproteinaemia
This is where neoplastic cells produce free Ig heavy chains. alpha chain disease is the most important, causing malabsorption from infiltration of small bowel wall. It may progress to lymphoma.
49
Describe Protein C+S deficiency and its features.
A type of thrombophilia. These vitamin K-dependent factors act together to cleave and so neutralise factors V + VIII.
Features:
- Heterozygotes deficient for either protein risk thrombosis. Skin necrosis also occurs.
- Homozygous deficiency for either protein causes neonatal purpura fulminans, fatal if untreated.
- Testing for protein C is done using snake venom to activate the protein C, which is then quantified by clotting methods.
50
Describe Antithrombin deficiency
Antithrombin is a co-factor of heparin, and inhibits thrombin. heterozygotes risk is greater than protein C or S deficiency by ~4-fold. Homozygosity is incompatible with life.
51
What are some causes of polycythaemia
May be absolute (increased RBC mass) or Relative (Normal RBC mass and decreased plasma volume)
Relative may be acute and due to dehydation (e.g. alcohol or diuretics)
Absolute causes may be primary (polycythaemia Rubra vera) or secondary due to hypoxia (e.g. high altitudes, chronic lung disease, cyanotic congenital heart disease, heavy smoking) or inappropriate erythropoietin secretion (e.g. renal carcinoma, hepatocellular carcinoma. Testosterone replacement can cause polycythaemia
52
Describe agranulocytosis and some common drug causes
Granulocytes (neutrophils, basophils, eosinophils) stop being made. It may present as a sore throat before a fatal infection so warn all patients to report any fever when starting a risk drug. If presents stop drug, and GCSF may have a role.
Important drugs to note are:
- Clozapine
- anti-thyroid e.g. Carbimazole
- anti-epileptics
- cytotoxics
53
What are some causes of a lymphocytosis?
- Acute viral infection
- Chronic infection e.g. TB, Brucella, Hepatitis, Syphilis
- Leukaemias and lymphomas, especially chronic lymphcytic leukaemia (often presents as incidental finding on FBC)
54
Describe Hodgkin's Lymphoma, its symptoms, tests, classification, and management.
Malignant proliferation of lymphocyte with characteristic mirror-image nuclei called Reed-Sternberg Cells. Peak incidence in young adults and elderly. It is the leading cause of malignancy if aged 15-24yrs.
Symptoms: Often presents with enlarged, painless, non-tender, rubbery superficial lymph nodes, typically cervical (60-70%), also axillary or inguinal. Node size may increase and decrease spontaneously and nodes can become matted. 25% have B symptoms e.g. Fever, weight loss, night sweats, pruritis, and lethargy. There may be alcohol induced lymph node pain.
Tests: Bloods, FBC (anaemia, lymphocytosis), film, ESR (raised), LFT, LDH (raised in increased cell turnover), Urate, Ca2+/Image guided needle biopsy + CT/MRI for staging
Grading:
I = one area involved
II = two or more areas involved
III = areas above and below diaphragm involved
IV = bone marrow involvement or other organ
A/B = Absence/presence of B symptoms
Classification:
- Nodular Sclerosing (70%)- most common good prognosis more common in women associated with lacunar cells
- Mixed cellulalrity (20%) - good prognosis associated with a large number of Reed-Sternberg cells.
- Lymphocyte predominant (5%) - best prognosis
- lymphocyte depleted - rare worst prognosis.
Treatment:
-Chemoradiotherapy, increases risk of secondary malignancy Common course is ABVD Adriamycin, Bleomycin, Vinblastine, Dacarbazine.
55
What are some causes of neutropenia?
- Viral infections
- drugs (e.g. Post chemotherapy, cytotoxic agents, carbamazepine, Sulfonamides
- Severe sepsis
- neutrophil antibodies (SLE, Haemolytic anaemia)
- hypersplenism e.g. Feltys
- bone marrow failure
56
Describe the basic interpretation of coagulation studies.
Two main coagulation pathways studied are the APPT and PT.
```
APPT = XII, XI, IX, VIII, X, V, II
PT = VII, X, V, II
```
Therefore if PT is increased and APPT is normal then the problem lies early in the cascade e.g. Factor VII, If APPT is raised and PT is normal then the factor lies early in the APPT cascade e.g. XII, XI, IX, VIII. If both are raised the problem lies with the late common part of the cascade e.g. X, V, II.
Mixing studies allows to further differentiation of the cause, normal plasma is added to the sample which should correct an abnormality if deficiency is an issue. If it does not correct the problem then an inhibitor is the cause of the prolonged bleeding time.
57
Describe Polycythaemia Rubra Vera, its presentation, investigations, and management.
A haemotlogical malignancy
Presentation: Incidental finding on FBC with nonspecific lethargy. A third present due to thrombosis e.g. Stroke, myocardial infarction, DVT, PE. May also suffer from headaches, dizziness, sweating, pruritis worse after hot baths. Splengomegaly. Hypertension.
Investigations: Hb over 18.5, JAK2 mutation, Bone marrow biopsy shows hypercellularity, low serum erythropoietin.
Management:
- long term phlebotomy
- low dose aspirin
- antihistamines for prurtis.
58
What is Virchow's triad?
A triad of factors thought to contribute to thrombosis:
- Hypercoagulability
- Haemodynamic changes (stasis/turbulence)
- Endothelial injury/dysfunction.
59
What are the contraindications to using NOACs?
Rivaroxaban, apixaban, dabigatran, indicated in prevention of stroke with people with non-valvular AF. No monitoring needed but can not be reversed (except dabigatran).
Contraindications: severe Renal impairment, NSAIDS, valvular disease
Lower rate of intracranial haemorrhage but increased risk in GI bleeding.
60
Describe Heparin-Induced Thrombocytopenia (HIT), its symptoms, and management.
A side-effect of heparin and more rarely LMWH. Caused by the formation of abnormal antibodies that activate platelets. Can be assessed using 4T score. Can be confirmed using ELISA test for anti-heparin-PF4 or more specifically Serotonin release assay.
Symptoms: Platelet count falls, mostly asymptomatic some get a systemic reaction such as fever, Hypertension, tachycardia, some may get rash.
Management:
- stop current heparin and try fondaparinux or argatroban
- do not start warfarin until platelet count is over 150 due to increased risk of warfarin necrosis in HIT.
61
What are the different coagulation disorders?
Congenital:
- Haemophilia A (Factor VIII deficiency, prolonged APPT)
- Haemophilia B (Factor IX deficiency, prolonged APPT)
- Von-Willebrands disease (most common, prolonged APPT)
Acquired:
- Anticoagulants
- Liver disease, Vit K deficiency needed for II, VII, IX, X (prolonged PT and APPT)
62
Describe Splenectomy, its indications, and management.
The spleen plays a vital immunological role acting as a reservoir for lymphocytes and in dealing with bacteraemias. A characteristic blood film is seen following splenectomy with howel-jolly bodies, pappenhemier bodies and target cells. Below advice also applies to hyposplenic patients e.g. Coeliac disease or sickle-cell anaemia.
Indications: Splenic trauma, hypersplenism, autoimmune haemolysis, ITP.
Management:
- early mobilisation as transient rise in platelets predisposes to thrombi
- immunisations, pneumococcal (very vulnerable), haemophilus influenza, menigococcal c at 2 weeks before. Men ACWY one month later. Annual influenza.
- lifelong prophylactic oral antibiotics (phenoxymethylpenicllin aka penicillin V 500mg BD or Amoxicillin 250mg BD). Erythromycin if pen-allergic.
- patient help cards alerting health professionals to infection risk
- advice to seek medical attention if any signs of infection
- urgent admission if infection develops
- if travelling abroad warn of risk of severe malaria and advise meticulous prophylaxis
63
What are the poor prognostic factors of ALL?
- Age less than 2 or over 10
- WBC over 20 at diagnosis
- T or B cell surface markers
- Non-Caucasian
- Male sex
64
Describe Waldenstrom's macroglobulinaemia and its features.
aka Lymphoplasmacytic lymphoma a malignancy affecting lymphoplasmacytoid and plasma cells, characterised by the secretion of monoclonal IgM paraprotein but an absence of light chains thus lack of renal involvement
Features: Weight loss, lethargy, hyperviscosity (prothrombotic, visual disturbance), hepatosplenomegaly, lymphadenopathy, cyroglobulinaemia.
65
Describe the Coomb's test and how this might help differentiate haemolytic anaemia
Coomb's test determines whether the cause of haemolytic anaemia is autoimmune in origin indicated by a positive test.
Direct vs Indirect: There are two types direct and indirect, direct involves mixing of the patients erythrocytes or serum respectively with reagents. +ve direct indicates antibodies on the erythrocytes and +ve indirect indicates antibodies in serum.
Warm vs Cold: the temperature at which erythrocytes agglutinate during the Coombs test can further differentiate auto-immune haemolytic anaemia.
- Warm (37C) IgG: cause include, idiopathic, CLL, lymphoma, SLE, RA, drugs e.g. Methyldopa.
- Cold (4C) IgM: causes include idiopathic, lymphoma, EBV, mycoplasma pneumoniae, HIV, SLE
66
What organisms does hyposplenism put one at risk of?
Encapsulated organisms e.g.
- strep pneumoniae (thus pneumococcal vaccine)
- haemophilus influenza
- nesseria menigitidis
- salmonella typhi
- klebsiella pneumonia
67
Describe Haemolytic anaemia, its features, and causes.
Haemolytic anaemia may be intravascular or extravascular.
Features: Anaemia with normal or increased MCV, raised unconjugated bilirubin (prehepatic jaundice), raised urinary urobilinogen, raised LDH (released from red cells), reticulocytosis (raised MCV, polychromasia)
Extravascular features:
-splenic hypertrophy and splenomegaly
Intravascular features:
- raised plasma haemoglobin
- methaemalbuminaemia
- decreased plasma haptoglobin
- haemoglobinuria
Causes:
Acquired:
-autoimmune (Coombs test +ve) e.g. drug induced (penicillin, quinine), autoimmune haemolytic anaemia, paroxysmal cold haemoglobinuria
-microangiopathic haemolytic anaemia e.g. HUS, TTP, DIC, pre-eclampsia
-infection e.g. malaria
-paroxysmal nocturnal haemoglobinuria
Hereditary:
-enzyme defects e.g. G6PD deficiency, pyruvate deficiency
-membrane defects e.g. Hereditary spherocytosis
-haemoglobinopathy e.g. sickle cell disease, thalassaemia
68
Describe Acute Promyelocytic Leukaemia, its features, and management
Aka Acute myeloid Leukaemia subset M3, the PML-RARA fusion gene has formed due to reciprocal translocation involving the long arms of chromosomes 15 + 17. RARA usually encodes for a receptor for teinoic acid, a Vitamin A derivative that is essential for myeloid lineage maturation.
Features: Disseminated intravascular coagulation (common presentation) Bone marrow suppression, weight loss raised WCC. Presents younger than other types of AML average 25yrs old. Good prognosis.
Management:
-complete remission on treatment with Vitamin A
69
Describe Vitamin B12 deficiency, its causes, features, and management.
Vitamin B12 is found in meat, fish and dairy products. Body stores are sufficient for 4yrs. It is Protein bound and release during digestion to which it is then bound to intrinsic factor for absorption in the terminal ilium.
Causes: Dietary e.g. Vegans, congenital metabolic errors.
Malabsorption:
-stomach e.g. Pernicious anaemia, post gastrectomy (lack of intrinsic factor)
-Terminal Ileum e.g. Crohn's, bacterial overgrowth, Coeliacs, resection
Features: Anaemia, mild jaundice, glossitis, angular cheilosis, peripheral neuropathy, psychosis, irritability, subacute degeneration of the cord (LMN + UMN signs), in pernicious anemia there are antibodies to paternal cell antibodies or intrinsic factor antibodies.
Management:
-malabsorption causes require hydroxocobalamin injections 1mg IM alternate days for 2 weeks then 1mg every three months for maintainence.
70
Describe Lysosomal storage disease, the types, and features.
A group of rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments onto other parts of the cell for recycling. This requires several critical enzymes, if one of these enzymes is defective large modules accumulate within the cell eventually killing it. Most are autosomal recessively, but a few are X-linked recessive (Fabry, Hunter)
Types:
- Lipid storage disorders e.g. Gauchers, Niemann-pick, Tay-Sachs
- Mucopolysaccharidoses e.g. Hunter and Hurler
- Glycoproteins storage disorders
- Glycogen storage disease
Features:
-Symptoms vary but can include, developmental delay, movement disorders, seizures, dementia, deafness, blindness, hepatomegaly, splenomegaly, pulmonary and cardiac problems, and abnormal bone growth
71
What are some drugs causes of pancytopenia?
```
Cytotoxics
Antibiotics e.g. Trimethoprim, chloramphenicol
Anti-rheumatoid e.g. Gold, penicillamine
Carbimazole
Carbamazepine
Sulphonylureas e.g. Tolbutamide
```
72
What are some poor prognostic factors in leukaemia?
Male
Less than 1yrs or over 9yrs
Relapse after treatment
Testes or meningeal involvement
73
Describe Paroxysmal Nocturnal Haemoglobinuria, its features, and management
An acquired disorder leading to haemolysis (mainly intravascular). Thought to be due to increased sensitivity of cell membranes to complement due to a lack of glycoproteins glycols-phosphatidylinositol (GPl), GPl acts as an anchor which attaches surface proteins to the cell membrane, thrombosis is though to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation.
Features:
- Haemolytic anaemia
- Pancytopenia is possible
- Haemoglobinuria
- Thrombosis e.g. Budd-Chiari syndrome
- Aplastic anaaemia may develop
Management:
- flow cytometry of blood to detect low levels of CD599 and CD55 has replaced Hams test (Acid-induced haemolysis)
- Blood product replacement
- anticoagulation
- Eculizumab (monoclonal antibody directed against terminal protein C5)
- Stem cell transplantation
74
Describe Hereditary Spherocytosis, its features, and management.
Most common hereditary haemolytic anaemia in people of Northern European descent. Autosomal dominant defect of red blood cell cytoskeleton, which are destroyed by spleen.
Features: Failure to thrive, jaundice, gallstones, splenomegaly, aplastic crisis precipitated by parvovirus, haemolysis, MCHC elevated, MCV low, diagnosed by osmotic fragility test
Management:
- folate replacement
- splenectomy
75
What are the different classifications of Primary immunodeficiency?
Neutrophil Disorders:
- Chronic granulomatous disease
- Chediak-Higashi syndrome
- Leukocyte Adhesion Deficiency
B-cell disorders:
- Common Variable Immunodeficiency
- Bruton's (X-linked) congenital agammaglobulinaemia
- Selective IgA deficiency
T-cell disorders:
-DiGeorge syndrome
Combined B- and T-cell disorders:
- Severe combined immunodeficiency
- Ataxia telangiectasia
- Wiskott-Aldrich syndrome
76
Describe Chronic Granulomatous Disease, its features, and investigations, and management.
A rare inherited neutrophil disorder due to lack of NADPH oxidase which reduces ability of phagocytes to produce reactive oxygen species.
Features: Recurrent pneumonias and abscess, particularly to catalase-positive bacteria e.g. Staph Aureus and fungi (Aspergillus)
Investigations:
- Negative nitroblue-tetrazolium test
- Abnormal dihydrorhodamine flow cytometry test
Management:
-Antibiotic prophylaxis +/- Bone marrow transplant
77
Describe Chediak-Higashi Syndrome and its features.
A neutrophil disorder due to a microtubule polymerisation defect which leads to a decrease in phagocytosis.
Features: Affected children have 'Partial Albinism' and peripheral neuropathy. Recurrent bacterial infections are seen. Giant Granules in neutrophils and platelets.
78
Describe Leukocyte adhesion deficiency and its features.
A neutrophil disorder caused by a defect of LFA-1 integrin (CD18) protein on neutrophils.
Features: Recurrent bacterial infections. Delay in umbilical cord sloughing may be seen. Absence of neutrophils/pus at sites of infection.
79
Describe Common Variable immunodeficiency
A B-cell disorder with many underlying defects. Hypogammaglobulinaemia is seen. May predispose to autoimmune disorders and lymphoma
80
Describe X-Linked Agammaglobulinaemia and its features.
Aka Bruton Syndrome. X-linked recessive B-cell disorder caused by a defect in Bruton's tyrosine kinase (BTK) gene that leads to a severe block in B cell development.
Features: Recurrent bacterial infections are seen. Absence of B-cells with reduce immunoglobulins of all classes.
81
Describe Selective IgA defiency, and its features.
Most common primary antibody deficiency and B-cell disorder caused by a maturation defect in B cells.
Features: Recurrent sinus and respiratory infections. Associated with coeliac disease and may cause false negative coeliac screen.
Severe reactions to blood transfusions may occur (anti-IgA antibodies lead to anaphylaxis
82
Describe DiGeorge syndrome and its features.
A T-cell disorder due to 22q11.2 deletion and failure to develop 3rd and 4th pharyngeal pouches.
Features: Congenital heart disease e.g. Tetralogy of Fallot, Learning Difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate.
83
Describe Severe Combined Immunodeficiency and its features.
A combined B- and T-cell disorder with many underlying defects most commonly a X-linked defect in common gamma chain, a protein used in the receptors for IL-2 and other interleukins. Other causes include adenosine deaminase deficiency.
Features: Recurrent infections due to viruses, bacteria and fungi. Reduced T-cell receptor excision circles.
Management:
-Stem cell transplantation may be successful.
84
Describe Ataxia Telangiectasia and its features.
An Autosomal Recessive combined B- and T-cell disorder caused by a defect in DNA repair enzymes.
Features include cerebellar ataxia, telangiectasia, recurrent chest infections (hypogammaglobulinaemia) and 10% risk of developing malignancy, lymphoma or leukaemia.
85
Describe Wiskott-Aldrich syndrome and its features.
An X-linked recessive combined B- and T-cell disorder caused by a defect in WAS gene.
Features: Recurrent bacterial infections, eczema, thrombocytopenia, Low IgM levels and increased risk of autoimmune disorders and malignancy
86
What are the safe transfusion rates for blood components?
Packed Red cells: Safely transfused over 90-120 minutes per unit, maximum 4 hours, during massive haemorrhage each unit over 5-10 units may be required.
Platelets: Usually transfused over 30-60minutes
Fresh Frozen Plasma: Infusion rate typically 10-20mL/Kg/hr, although more rapid may be appropriate in major haemorrhage
Cryoprecipitate: Typically transfused at 10-20mL/Kg/hr (30-60 min per 5-unit pool)
87
Describe Transfusion-Associated Circulatory Overload (TACO), its features, and management.
Acute or worsening pulmonary oedema within 6 hours of transfusion. Prevent by giving blood slowly and pre-transfusion diuretics (e.g. Furosemide 40mg IV)
Features: Respiratory distress, tachycardia, hypertension, evidence of fluid overload.
Management:
-Stop transfusion, give oxygen, and diuretic therapy.
88
Describe Sideroblastic anaemia, its causes and management.
A condition where red cells fail to completely form Haem. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired.
Causes:
- Congenital: delta-aminolevulinate synthase-2 defiency
- Acquired e.g. Myelodysplasia, alcohol, lead, anti-TB mess
Management:
- supportive
- treat underlying cause
- Pyridoxine may help
89
What are the indications for Plasmapheresis (Plasma exchange)?
- Guillain-Barre Syndrome
- Myasthenia Gravis
- Goodpasture’s syndrome
- ANCA positive vasculitis e.g. Wegner’s, Churg-Strauss
- TTP/HUS
- Cyroglobulinaemia
- Hyper-viscosity Syndrome e.g. secondary to myeloma.
90
What is the dose of Beriplex in bleeding with DOACs?
25IU/Kg
91
Describe the dose of Protamine sulphate in bleeding with heparin.
1mg neutralises 100IU heparin. Do not give more than 50mg in one dose.
92
What are the main types of T-Helper cells and their role?
Two major subsets of T-Helper cells.
Th1: Involved in the cell mediated response and delayed (Type IV) hypersensitivity. They secrete IFN-gamma, IL-2, IL-3
Th2: Involved in mediating humoral (antibody) immunity e.g. stimulating production of IgE in asthma. Secrete IL-4, IL-5, IL-6, IL-10, IL-13
93
What is the Leucocyte Alkaline phosphatase score?
Often used in patients with elevated WBC to differentiate a reactive process from chronic myelogenous leukaemia. Leukocyte Alkaline phosphatase is found within mature WBC’s. Higher levels are seen in pathologies of mature WBC’s whereas a low score is found in pathologies involving underdeveloped leucocytes.
Raised in:
- Myelofibrosis
- Leukaemoid reactions
- Polycythaemia Rubra Vera
- Infections
- Steroids, Cushing’s syndrome
- pregnancy, oral contraceptive pill
Low in:
- Chronic myeloid leukaemia
- Pernicious anaemia
- Paroxysmal Nocturnal haemoglobinuria
- Infectious mononucleosis
94
Describe Haemophagocytic Lymphohistiocytosis, its features, investigations, and management.
An uncommon haematological disorder seen more often in children than adults. It is a life-threatening Disease of severe inflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. It is classified as one of the cytokine storm syndromes
Features: Fever, hepatosplenomegaly, Lymphadenopathy, Jaundice, rash.
```
Investigations:
-Pancytopenia
-Bone marrow may show haemophagocytosis
-LFTs deranged and Albumin low
CRP, ESR and Ferritin are markedly elevated (in children a ferritin above 10000 is very sensitive and specific for HLH)
-Fibrinogen is low and D diner elevated.
-Hypertriglyceridaemia
-Soluble CD25 (soluble IL-2 receptor)
```
Management:
- High dose corticosteroids, etoposide, ciclosporin.
- IVIg may be used.
- Methotrexate and vincristine have also been used.
95
Describe Leukaemoid reactions and its causes.
The leukaemoid reaction describes the presence of immature cells such as myeloblasts, promyelocytes and uncleared red cells in the peripheral blood. This may be due to infiltration of the bone marrow causing the immature cells to be ‘pushed out’ or sudden demand for new cells.
Causes:
- Severe infection
- Severe haemolysis
- Massive Haemorrhage
- Metastatic cancer with bone narrow infiltration.
96
How does one differentiate between a leukaemoid reaction and chronic myeloid leukaemia?
Leukaemoid reaction:
- High leucocytes alkaline phosphatase score
- Toxin granulation (Dohle bodies) in the white cells
- ‘left shift’ of neutrophils i.e. three or less segments of the nucleus
Chronic myeloid leukaemia:
-Low leucocyte alkaline phosphatase score.
97
Describe Hairy Cell leukaemia, its features, and management.
Hairy cell leukaemia is a rare malignant proliferation disorder of B cells. It is more common in males (4:1). The typical hair cells are named because of the characteristic cystoplasmic projections which appear as microvilli when seen by light microscopy
Features:
- Monocytopenia
- Splenomegaly
- Skin vasculitis in 1/3 of patients
- 'Dry tap' despite bone marrow hypercullarlity
- Tartrate resistant acid phosphotase (TRAP) stain positive.
Management:
- Chemotherapy is first line, Cladribine, pentostatin
- Immunotherapy is second line, rituximab, interferon-alpha.
98
Describe Monoclonal Gammopathy of Undetermined Significance (MGUS) and its features.
MGUS aka benign paraproteinaemia and monoclonal gammopathy, is a common condition that causes a paraproteinaemia and is often mistaken for myeloma. Around 10% of patients eventually develop myeloma at 5 years with 50% at 15years.
Features:
- Usually asymptomatic
- No bone pain or increased infections
- Around 10-30% of patients have a demyelinating neuropathy
Differentiating features from myeloma:
- Normal immune function
- normal beta-2 microglobulin levels
- Lower level of paraproteinaemia than myeloma (e.g. less than 30 IgG or 20 IgA)
- Stable level of paraproteinaemia
- No clinical features of myeloma e.g. mythic lesions on x ray or renal disease
99
What malignancy is the translocation T9:22 associated with?
Chronic myeloid Leukaemia ( 9 ABL (oncogene an aberrant tyrosine kinase + 22 B receptor)
100
What malignancy is the translocation T15:17 associated with?
Acute Pro-myelocytic leukaemia ( 15 promyeloctic gene + 17 retinoid acid receptor alpha (fusion protein binds retinoid acid receptor and promotes transcription))
101
What malignancy is the translocation T8:14 associated with?
Burkitt's Lymphoma (8 c-myc (oncogene) + 14 Ig heavy constant region)
102
What malignancy is the translocation T14:18 associated with?
Follicular lymphoma (14 Ig heavy constant region + 18 BCL2 (anti-apoptotic gene))
103
What malignancy is the translocation T11:14 associated with?
Mantle Cell lymphoma (11 - cyclin D (oncogene) + 14 Ig Heavy constant region)
104
Describe Sezary syndrome and its features
A type of T-cell cutaneous lymphoma.
Features:
- Pruritus
- erythroderma typically affecting the palms, soles and face
- atypical T cells
- lymphadenopathy
- Hepatosplenomegaly.
105
Describe Microangiopathic Haemolytic Anaemia (MAHA) and its causes
A subgroup of haemolytic anaemia caused by factors in the small bloods vessels identified by finding of anaemia and schistocytes on microscopy/blood film. Damage in endothelial layer of small vessels results in fibrin depositions and platelet aggregation. as red blood cells travel through these damaged vessels they are fragments resulting in intravascular haemolysis
Causes: Haemolytic Uraemic syndrome, Disseminated intravascular coagulation, thrombotic thrombocytopaneic purpura, malignant hypertension.
106
Describe Haemolytic Uraemic Syndrome, its features, causes, and management
Generally seen in young children it produces a triad of acute renal failure, microangiopathic haemolytic anaemia and thombocytopaenia. It is most common cause of AKI in children. Endothelial damage commonly (90%) from E.coli strain O157 leads to thrombosis, platelet consumption and fibrin strand deposition mainly in renal microvasculature. Strands cause mechanical destruction of RBC's giving triad of haemolysis, thrombocytopenia and AKI.
Features: Abdominal pain, bloody diarrhoea and AKI.
Causes:
- post-dysentry - (classically E.coli O157:H7)
- tumours
- pregnancy
- ciclosporin, the pill
- SLE
- HIV
Management:
- Treatment is supportive - IV Fluids, Blood transfusion and dialysis if required.
- No role for antibiotics
- Indications for plasma exchange are complicated in general plasma exchange is reserved for severe cases of HUS not associated with diarrhoea.
107
What are the indications for CMV negative and irradiated blood?
CMV is transmitted in leucocytes. As most blood products except granulocyte transfusions are now leucocyte depleted CMV negative products are rarely required.
- Granulocytes transfusions
- Intra-uterine transfusions
- Neonates up to 28days post expected date of delivery
- Pregnancy: Elective transfusion during pregnancy (not during labour or delivery)
Irradiated blood products are used to avoid transfusion graft versus host disease caused by engraftment of viable donor T lymphocytes.
- Granulocytes transfusions
- Intra-uterine transfusions
- Neonates up to 28days post expected date of delivery
- Bone marrow / stem cell transplants
- immunocompromised e.g. chemotherapy or congenital
- Patients with/previous Hodgkins disease
- HIV
108
Which features may suggest underlying inherited thrombophilia in context of VTE?
- Thrombosis at young age (less than 50)
- Strong family history of VTE (First degree relatives)
- Recurrent VTE
- VTE in unsusal sites e..g splanchic or cerebral veins.
Test 2 weeks after warfarin if high risk or 2 days after DOAC.
109
Describe Smoldering Multiple Myeloma
An asymptomatic clonal plasma cell disorder. An intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. The risk progression per year is 10% vs 1% in MGUS.
Defined by the presence of a serum monoclonal M protein over 3g/dL. or 10-60% clonal bone marrow plasma cells with no evidence of end organ damage.
110
Describe Factor V Leiden
A variant mutated form of Human Factor V which causes hyper coagulability. This mutation prevents activated protein C a protein which normally inhibits the pro-clotting activity of factor V from binding leading to a hyper coagulable state. It is the most common hereditary hyper coagulability disorder amongst ethinic europeans.
111
Describe Methaemoglobinaemia, its causes, features and management
A condition caused by elevated levels of Methaemoglobin, a form of haemoglobin that contains the ferric Fe3+ form of iron. This affinity for oxygen of ferric iron is impaired. It causes increased affinity of oxygen in the remaining ferrous haem sites leading to an overall reduced ability to release oxygen to tissues. Thus shifting the Oxygen -dissociation curve to the left.
Causes:
- Acquired e.g. Antibiotics (Trimethoprim, sulphonamides, dapsone), local anaesthetics (articaine, lidocaine), aniline dyes, metoclopramide,, rasburicase, ingestion of compounds containing nitrates such as bismuth nitrate.
- congenital e.g. deficiency of enzyme Diaphorase I (NADH-cytochrome b5 reductase) usually autosomal recessive. May also rise in patients with pyruvate kinase deficiency or G6PD deficiency.
Features: SOB, Cyanosis, Confusion, headache, fatigue, exercise inolterance, dizziness, seizures.
Management:
-Oxygen and Methylene blue 1% solution (10mg/mL) 1-2 mg/kg administered slowly over five minutes. (inhibits monoamine oxidase and serotonin toxicity can occur if taken with an SSRI)
112
Describe Febrile Non-Haemolytic Transfusion reactions.
A type of transfusion reaction that is associated with fever but not directly haemolysis. It is most commonly caused by antibodies directed against donor leukocytes and HLA antigens. Can also be mediated by preformed cytokines in the donor plasma as a consequence of white blood cell breakdown. Most blood products are white cell depleted but not completely so still can occur.
113
Describe Transfusion-associated lung injury. and its features.
A serious blood transfusion complications. Donor plasma has antibodies directed against the recipient HLA antigens, mediating characteristic lung damage. Usually occurs with platelets and FFP but can rarely occur with RBCs.
Features:
-Acute onset of non-cariogenic pulmonary oedema. (SOB, Hypoxia, Hypotension) usually develops within 6 hours of transfusion
114
What is haptoglobin?
A plasma protein that binds free Haemoglobin released from erythrocytes. Haptoglobin-Haemoglobin is the removed by the reticulodendothelial system (Mostly the spleen). Can differentiate intravascular and extravascular haemolytic anaemias but is not reliable.
115
What are the differences between bone marrow biopsy (Trephine) and Bone marrow aspiration?
Aspiration:
- Fast
- Gives relative quantity of different cell types
- gives material to further study e.g. molecular genetics and flow cytometry
- Does not represent all cells
Biopsy (Trephine):
- Gives cell and stroma constitution
- Represents all cells
- Explains cause of dry tap
- Slow processing
116
Describe myelofibrosis, its types and features
Myelofibrosis a classified as a myeloproliferative disorder.
Types:
- primary where there is proliferation of fibroblasts
- secondary develops from polycythaemia vera or essential thrombocythaemia.
Features: Splenomegaly, bone pain, bruising, cachexia, fatigue, gout, anaemia.
117
What are pappenheimer bodies?
Abnormal basophilic granules of iron found inside red cells on routine blood stain. They appear as dense, blue-purple granules within the red blood cell usually only on or two located in the cell periphery.
They are mostly observed in post-splenectomy states and in disease such as myelodysplastic syndrome, sideroblastic anaemia, haemolytic anaemia, lead poisoning, and sickle cell disease.
118
Describe Congenital Pelger-Huet Anomaly, and its features
A laminopathy associated with mutations in the lamin B receptor. This leads to bilobed nuclei in neutrophils and in homozygotes, can also be associated with skeletal abnormalities which include shortened limbs. Heterozygotes usually suffer no symptoms and the neutrophil anomaly is picked up incidentally.
119
Describe cryoglobulinaemia,and its types.
Presence of cyroglobulin (Proteins the precipitate in cold) can be divided into three types.
Type 1: A monoclonal usually IgM. The most common cause of type 1 is an immunoglobulin-producing cancer (Waldenstroms macroglobulinaemia or multiple myeloma)
Type 2: is also monoclonal but this time the cryoglobulin binds to polyclonal IgG and is henced often termed ‘mixed cryoglobulin’. The classic setting for type 2 is chronic viral infection (especially Hep C and HIV - but not Hep B)
Type 3: Is entirely polyclonal and usually associated with an underlying connective tissue disease especially Sjögren s syndrome.
Both type 2 and 3 can have rheumatoid factor activity so may be associated with positive RhF
120
What is the common chemotherapy schedule for Hodgkin’s disease?
ABVD
Adriamycin, Bleomycin, Vincristine, Dacarbazine
121
What is the common chemotherapy schedule for high grade non-hodgkins lymphoma?
CHOP
Cyclophosphamide
Hydroxydaunomycin (Doxorubicin)
Oncovin (Vincristine)
Prednisolone
Also R-CHOP R = Rituximab
122
What is the common chemotherapy schedule for chronic lymphocytic leukaemia?
FCR
Fludarbine
Cyclophosphamide
Rituximab
(Chlorambucil when fludarbine fails or is contraindicated)
123
What is the common chemotherapy schedule for multiple myeloma?
CDT
Cyclophosphamide
Dexamethasone
Thalidomide
Bortezomib if alternative to thalidomide if not tolerated/contraindicated
124
What is the common chemotherapy schedule for acute myeloid leukaemia?
Cytosine ad an anthracycline
125
What is a common chemotherapy schedule for acute lymphoid leukaemia?
Vincristine and steroid
126
Describe the International Scoring System for Multiple Myeloma.
Staging based on serum B2 Microglobulin and Albumin level.s
Stage 1: Serum B2 microglobulin less than 3.5mg/L AND serum albumin more than 3.5g/dL. (Mean survival 62months)
Stage 2: Either Serum B2 microglobulin less than 3.5mg/L but albumin less than 3.5 OR serum B2 microglobulin 3.5-5.4 mg/L irrespective of the serum albumin (Mean survival 45 months)
Stage 3: Serum B2 microglobulin over 5.5mg/L (Mean survival 29 months)
127
Describe Paroxysmal Cold Haemoglobinuria, its features and management.
Aka Donath-Landsteiner syndrome. An autoimmune haemolytic anaemia featured by complement mediated intravascular haemolysis after cold exposure.
Features: Acute onset fatigue, exercise intolerance, pallor, jaundice and haemoglobinuria, preceded by exposure to cold temperature and preceding viral like illness. Bloods show MAHA type picture reduced haptoglobin increased bilirubin, anaemia. Coombs test +VE
Management:
- Usually transient and self limiting
- plasmapheresis may have a role
128
What features can help differentiate Beta-Thalassaemia from IDA?
Iron Deficency Anaemia:
- Normal or reduced A2 level
- Any level of anaemia
- Any Ethnic group
- MCV inkeeping with degree of anaemia
- Low serum ferritin
- Low iron saturation
Beta-Thallassaemia:
- Raised HB A2
- Hb usually less than 90
- Mediterranean or Asian
- surprisingly low MCV for degree of anaemia
- Normal Ferritin
- Normal Iron saturation
129
What are the causes of target cells?
Haemoglobinopathies, Thalassaemias
Iron Deficiency
Liver disease
Post-splenectomy
130
What is the management of Anti-Phospholipid Syndrome in pregnancy?
Antibodies +ve but no prior events:
-Consider antepartum LMWH depending on other risk factors.
Prior VTE:
-LMWH
Prior Pregnancy morbidity:
-Aspirin + LMWH
131
How long does Vitamin K reversal take?
4-6Hours
132
What is Ristocetin and what role does it play in vWF Activity?
It is antibiotic through an unknown mechanism causes vWF to bind the Platelet Receptor glycoproteins 1b, so when added to normal blood causes agglutination. The property is utilised in measurement of vWF activity
133
Describe POEMS Syndrome, and its features
POEMS syndrome is a rare multi-system disease that occurs in the setting of plasma cell dyscrasia. It involves polyneuropathy of both motor and sensory nerves, begins distally and has a progressive proximal spread. Associated cranial or autonomic nerves are not involved. Both demyelination and axonal degeneration are noted.
134
What is the diagnostic Criteria for DIC?
Risk Assessment: Does the patient have an underlying disorder known to be associated with overt DIC?
```
Scoring:
Platelets:
- more than 100 = 0
- Less than 100 = 1
- Less tan 50 = 2
```
Elevated Fibrin marker (D-dimer):
- No increase = 0
- Moderate increase = 1
- Strong increase = 2
Prolonged PT:
- less than 3s = 0
- More than 3 but less than 6 = 1
- more than 6 = 2
Fibrinogen level:
- More than 1g/l = 0
- Less than 1g/L = 1
Calculate Score:
- More than 5 compatible with Overt DIC
- Less than 5 suggestive for non-overt DIC.
135
What is eltrombopag?
A medication used to treated Thrombocytopaenia. It is a molecular agonist of the c-PML (TpoR) receptor which is the physiological target of the hormone thrombopoietin.
