Haematology Flashcards

1
Q

Causes of secondary thromocytosis?

A

Bleeding, infection, trauma, thrombosis, infarction, Fe deficiency, hyposplenism

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2
Q

Acquired thrombophilias?

A

Antiphospholipid antibodies
Polycythaemia
Thrombocythaemia

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3
Q
Antophospholipid syndrome
What antibodies?
Presentation?
Coagulation results?
Diagnosis?
A

Abs = lupus anticoagulant, anticardiolipin Abs, anti-beta 2 glycoprotein 1 Abs

Presentation = recurrent thromboembolism/miscarriage

Coagulation = prolonged. More sensitive test is DRVVT (dilute Russell viper venom time)

Diagnosis =

  • Presence of Abs on repeat test 12 weeks apart
  • Failure of coagulation tests to correct on addition of normal plasma
  • Coagulation tests correct on addition of excess phospholipids
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4
Q

Indications for exchange transfusion in sickle cell disease?

A

Frequent severe pain crisis
CNS sickling
Chest syndrome unresponsive to conservative Mx
Priapism
Peri-operatively/pregnancy i history of bad sickling

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5
Q

Cause of polychromasia?

A

Young RBC

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6
Q

Cause of teardrop RBCs?

A

Myelofibrosis

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7
Q

Chronic lymphocytic leukaemia
Features of poor prognosis?
Indications for management?
Management?

A

Prognosis

  • male, >70
  • lymphocyte >50, polymorphs >10%, doubling time <12 months
  • raised LDH
  • CD38 +ve, TP53 mutation
  • 17p deletion

Indications

  • Progressive marrow failure
  • Massive >10cm/progressive lymphadenopathy
  • Massive >6cm/progressive splenomegaly
  • Progressive lymphocytosis: >50% in 2 months or doubling in 6
  • Systemic symptoms: weight loss >10% in 6 months, fever >38 for 2 weeks, extreme fatigue, night sweats
  • Autoimmune cytopaenias

Management

  • Often none required
  • PRIOR TO CHEMO: p53 tumour suppressor gene analysis. Deletion/mutation = worse prognosis + resistance to standard chemo
  • Chemo of choice = FCR (Fludarabine, cyclophosphamide, rituximab)
  • Fludarabine is associated with profound lymphopenia. Prophylactic Co-trimoxazole essential to avoid pneumocystitisi no
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8
Q

Cause of spherocytosis?

A

Any haemolytic anaemia

Hereditary spherocytosis

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9
Q

Cause of sideroblastic anaemia?

A

Failure to incorporate Fe in Hb molecule –> Fe accumulation in mitochindria

Congenital
Acquired primary - myelodysplastic disorder
Acquired secondary - Alcohol, malignancy, drugs (e,g, anti-TB), connective tissue disorder, heavy metal poisoning

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10
Q
Multiple Myeloma
Definition?
Clinical presentation?
Pathologic features?
Imaging?
A

Clonal proliferation of plasma cells producing a monoclonal Ig. Clonality = all diseased cells originating from one parent cell

Presentation

  • CRAB: Ca elevated, Renal dysfunction, Anaemia, Bone disease
  • Also common: weight loss, fatigue
  • Less common: parasthesia, hepato/splenomegaly, fever

Pathologic features

  • Monoclonal protein in majority on serum electrophoresis. IgG most common then IgA then kappa/lambda light chain only then IgD/A/M. hypogammaglobulinaemia of unaffected Ig may be seen (all of them in non-secretory myeloma).
  • BM biopsy. Clonal plasma cell >10% if major criteria for diagnosis
  • Urinealysis: myeloma cast nephropathy –> negative dip. Renal involvement e.g. AL amyloidosis/light chain deposition –> positive dip. bence Jones protein seen in light chain only myeloma
  • Peripheral smear: rouleaux formation most common. May see leukopenia/thrombocytopenia

Imaging = whole body MRI to investigate for bone disease

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11
Q

Causes of folate deficiency?

A

Poor intake
Malabsorption (IBD/surgical resection)
Inc. requirement - pregnancy, haemolysis

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12
Q

Cause of sickle cell disease?

A

valine substituted for glutamic acid in position 6 of beta globin chain on chromosome 11

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13
Q

Clinical syndromes in sickle cell disease
Cause?
Possible precipitants?
Examples?

A
Cause = occlusion of small blood vessels by sickled cells
Precipitants = hypoxia, dehydration, infection. Often none identified
Examples = Pain crisis, chest syndrome, vaso-occlusive stroke, priapism, dactylitis, splenic sequestration crisis, aplastic crisis
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14
Q
Acute Promyelocytic leukaemia
Associated chromosomal abnormality? 
Histology?
Unique clinical feature?
Treatment?
A

Chromosome abnormality = t(15;17)
Fusion of PML and RAR-alpha (retinoic acid receptor)

Histology - Auer rods, faggot cells

Clinical feature = DIC/thrombocytopenia often at presentation

Treatment

  • DIC –> tranexamic acid, FFP, platelets
  • All-trans retinoic acid
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15
Q

Management of sideroblastic anaemia?

A

Remove cause if able
High dose pyridoxine + folate
?Erythropoeitin
RBC Tx - can worsen Fe overload

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16
Q

What is Felty’s syndrome?

A

Rheumatoid arthritis + splenomegaly + neutropenia

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17
Q

Multiple myeloma vs MGUS?

A

MM Vs MGUS

  • High paraprotein vs low paraprotein (<30 g/L for IgG)
  • Rising paraprotein vs stable paraprotein
  • Other Ig levels low vs other Ig levels normal
  • CRAB vs no CRAB
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18
Q

Use of hydroxycarbamide in sickle cell disease?

Side effects?

A

Used to increase HbF levels

SEs: BM suppression, subfertility, teratogenicity

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19
Q

Cause of fragmented RBCs?

A

MAHA

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20
Q

Causes of macrocytosis with normoblastic BM?

A
High reticulocyte count
Liver disease (impaired lipid manufacturing for RBC membrane)
Alcohol (BM toxicity, liver disease)
Myxoedema
Pregnancy
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21
Q

Aplastic anaemia
Blood results?
Causes?

A

Bloods = pancytopenia. Reduced reticulocyte count

Idiopathic (autoimmune)
Drugs - anti-thyroid, anti-seizure, gold etc.
Post-hepatitis (virus affects hepatocytes + BM stem cells)
Chemotherapy/radiation (e.g. azathioprine/mercaptopurine in Pts with low thiopurine methyltransferase levels)

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22
Q

Indications for splenectomy?

Changes seen after splenectomy?

A

Traumatic rupture
Autoimmune destruction of blood cells
Haematological malignancy (associated with massive splenomegaly/pain/other complications)
Congenital haemolytic anaemias

Changes

  • Howell-Jolly bodies (nuclear remnants in RBCs)
  • Target cells, thrombocytosis, increased aniso + poikilocytosis
  • Decreased IgM. Polyclonal T lymphocytosis. Enhanced neutrophilia in infection
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23
Q

Chronic lymphocytic leukaemia
Clinical features?
Blood results?
Investigation of choice?

A

Features

  • Commonly asymptomatic detected on routine bloods
  • B symptoms
  • Painless lymphadenopathy. Splenomegaly (less common than CML), hepatomegaly, skin manifestations
  • Acquired immunodeficiency, immune complications (e.g. haemolysis, thrombocytopenia)
  • Lymphocytosis –> high viscosity

Bloods

  • Lymphocytosis
  • ?cytopenias. Usually mild
  • ?hypo/hyper gammaglobulinaemia

Investigation = Immunophenotyping

  • 95% of cases are B cell lineage
  • B cell: CD19, CD23
  • T cell: CD5
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24
Q

Thrombotic Thrombocytopaenic Purpura
Pathology & causes?
Clinical & biochemical features?
Main management?

A
Path = ADAMST13 deficiency --> failure to cleave high molecular weight vWF --> formation of platelet microthrombi
Causes = post infection, pregnancy, tumours, SLE, HIV, drugs (e.g. ciclosporin, OCP, penicillin)
Clinical = often fever, cerebral & cardiac dysfunction. Renal dysfunction less marked than in HUS
Biochemical = typical MAHA, thrombocytopaenia, normal coagulation. Reduced ADAMST13

Management = FFP infusion + plasma exchange

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25
Diagnostic criteria for multiple myeloma?
``` Diagnosis - Clonal BM plasma cells >10% AND EITHER of the following - Related organ or tissue damage (CRAB) - Biomarker of near inevitable progression to end organ damage (SliM - Sixty% clonal plasma cell in BM, Light chain ratio >100, MRI with 1 or more focal lesions) ```
26
Disseminated Intravascular Coagulation Laboratory features? Causes?
Lab features - All coagulation prolonged - Low fibrinogen, high fibrin degradation products - Cosumption thrombocytopenia Causes - Obstetric: retroplacental haemorrhage, retained fetus, amniotic embolism, severe pre-eclampsia - other: crush, sepsis (esp. tosin producing staph aureus, clostridia), Haemolytic blood Tx reaction, Malignancy (esp associated with tumour cell necrosis)
27
Alpha thalassaemia genotypes?
Normal = (aa)(aa) a+ Heterozygous (a-)(aa) = mild microcytosis, no anaemia a+ heterozygous (a-)(a-) OR ao homozygous (aa)(--) = slightly anaemia. Low MCV HbH disease (a-)(--)= microcytic + hypochromic anaemia with splenomegaly. tetramer of b Hb form HbH Major (--)(--) = death in utero
28
``` Hodgkin's Lymphoma Common clinical features? Histology and subtypes? Blood findings? Staging? Management? ```
Clinical - Lymphadenopathy (non-tender, rubbery) - Mediastinal mass --> cough, SOB, chest pain. Effusions are uncommon. SVC syndrome rare. - B symptoms - Pruritis - Alcohol induced pain less common Histology: - Reed-Sternberg cells (Giant cell often with mirror image nuclei) Subtypes: - Lymphocyte predominant = reactive T cell infiltration (best prognosis) - Nodular sclerosis = fibrous bands separate nodules of Hodgkin's tissue (most common 70%) - Mixed picture - Lymphocyte depleted = no infiltrating lymphocytes (worst prognosis) Bloods - Common: Neutrophilia, thrombocytosis, anaemia. May be eosinophilia - Raised ESR - Raised LDH (guide to volume of disease)
29
Haemloytic uraemic syndrome Causes? Triad of features? Management?
Hereditary = complement gene mutations, coagulation pathway mutations, cobalamin C mutations Acquired infectious = shiga producing E coli 0157 (90% of cases), strep pneumoniae, HIV Acquired non-infectious = complement Abs, drugs, other conditions (e.g. SLE, pregnancy) Features - MAHA (anaemia, schistocytes) - Thrombocytopenia - Deranged kidney function Management - Supportive - Severe disease ?ecilizumab (complement C5 Ab) ?plasma exchange
30
Causes of macrocytic anaemia with megalobblastic errythropoeisis?
B12 deficiency Folate deficiency Drugs affecting BM DNA synthesis (e.g. methotrexate, azathioprie, hydroxycarbamide)
31
Immune thrombocytopenia Associated conditions? Management?
Associated = SLE, autoimmune haemolytic anaemia, viral infections (HIV, hep C, EBV), antiphospholipid syndrome, helicobacter gastritis Management - Steroids - IV Ig if life threatening bleeding and platelet Clint needs to rise quickly - steroid resistant --> splenectomy, IV IG, anti-D in D+ve (coats RBCs which are then preferentially destroyed), rituximab
32
Causes of haemolysis?
Autoimmune (cold agglutinin, warm AIHA, PNH) Congenital (haemoglobinopathies, RBC membrane defects e.g. spherocytosis, RBC enzyme defects e.g. G6PD deficiency) DIC Drug induced (immune, G6PD, thrombotic microangiopathy) Transfusion (acute & delayed reaction) Other (mechanical at heart valves, RBC parasite e.g. malaria, thrombotic microangiopathy, clostridial sepsis etc.)
33
Causes of microangiopathic haemolytic anaemia?
``` DIC Haemolytic uraemic syndrome Thrombotic thrombocytopeanic purpura Malignant HTN Severe pre-eclampsia ```
34
``` Anticoagulants LMWH mechanism + monitoring? Warfarin mechanism? Dabigatran mechanism? Rivaroxaban mechanism? Apixaban mechanism? ```
LMWH - Anti-factor Xa. Weak antithrombin compared to heparin - Monitor with anti-Xa levels with prolonged courses Warfarin - Inhibits hepatic synthesis of vitamin K dependent factors (2, 7, 9, 10, protein C). Initially prothrombotic = requires bridging anticoagulation on initiation. Dabigatran - Direct thrombin inhibition Rivaroxaban & apixaban - Direct Xa inhibition
35
``` Coagulation pathway What does PT measure? What does APTT measure? What does thrombin time measure? What is INR derived from? ```
PT = extrinsic & final common pathway APTT = intrinsic and final common pathway TT = Last part of final common pathway INR is derived from PT
36
Cause of elliptocytosis?
Hereditary elliptocytosis
37
Hodgkin's Lymphoma Staging? Management?
Staging = Ann Arbor - Stage I = 1 lymph node group - Stage II = Two nodal groups on one side of diaphragm - Stage III = Nodes on both sides of diaphragm - Stage IV = Extranodal tissue (excluding spleen) Management - Stage I --> radiotherapy - More advanced --> chemo. Most popular = ABVD (Adriamycin, bleomycin, vinblastine, dacabazine) - Relapse --> stem cell autografts + salvage chemo ESHAP (Etoposide, cytosine Arabinoside, High dose steroids, cisPlatin)
38
Infection prophylaxis for hyposplenic patients?
- Vaccines: pneumococcal, Haemophilus influenzae, meningitis C - Prophylactic lifelong BD phenoxymethylpenicillin or erythromycin in pen allergic (If Pt declines then take home amoxicillin to use at signs of infection) - Careful antimalarial prophylaxis + measures (spray, nets)
39
Neutropenic sepsis Definition? Treatment?
Neut <0.5 in Pt having anti-cancer treatment (typically 7-14 days after) with: fever >38 or a picture consistent with sepsis Treatment: - Tazocin ASAP - No improvement after 4-6/7 ?fungal cause - G-CSF in some patients
40
``` Von Willebrand's disease Clinical features? Cause? Blood test results? Management? ```
Features = platelet bleeding - Bruising, purpura, menorrhagia, epistaxis, bleeding from cuts + mucous membranes Cause = defective vWF production. Gene on Chromosome 12 Bloods - Low vWF antigen measured on immunological assay - Low FVIII clotting activity assay - Abnormal risocetin cofactor assay (risocetin is an Abx that clumps platelets in normal blood) - Prolonged bleeding time Management - DDAVP (synthetic ADH) if mild disease - FVIII concentrate (also contains vWF) in severe
41
General features of haemolysis seen on blood?
Commonly macrocytic anaemia High reticulocyte count High LDH and bilirubin, low haptoglobin Abnormal RBC morphology (esp. spherocytes)
42
``` Macrophage activation syndrome Presentation? Lab features? Diagnosis? Management? ```
Associated with rheumatological conditions Commonly presents with pancytopenia and intercurrent infection (esp. EBV) Lab = Excess hyperferritinaemia, raised triglycerides, deranged LFTs, hypofibbrinogenaemia Diagnosis = haemophagocytosis on BM biopsy Management - immunosuppression
43
Chronic myeloid leukaemia Clinical features? Blood & marrow features? Treatment?
Clinical - Tiredness, weight loss, sweating - Splenomegaly 90% - Hyperleukocytosis: visual disturbance, priapism, deafness, confusion - Gout Blood & marrow - Raised WCC, massive neutrophilia with left shift, absolute basophilia & eosinophilia, anaemia, variable platelet count - High B12 (WCs produce B12 binding protein) - BCR-ABL/t(9;22)/Philadelphia chromosome in >95% of cases - Marrow hyperplasia/fibrosis, increased stem cells Treatment - Tyrosine kinase inhibitors e.g. imatinib - Blood BCR-ABL measurements to monitor treatment - ?Stem cell transplant in young & fit unresponsive to imatinib
44
What do direct and indirect antiglobulin test look for?
``` Direct = Antibody on patients RBCs Indirect = Antibody in patient serum ```
45
Causes of B12 deficiency?
Poor intake Lack of intrinsic factor (pernicious anaemia, gastrectomy) Malabsorption (resection of/IBD affecting terminal ileum) Competitive consumption - colonisation of bowel with B12 consuming bacteria
46
Myelodysplastic syndromes definition?
Group of malignancies characterised by clonal haematopoeisis, one or more cytopenias and abnormal cellular maturation. Similar to AML but with lower blast percentage (<20). At risk of transformation to AML
47
``` Pernicious anaemia Cause? Associations? Investigations? Management? ```
``` Cause = Autoimmune attack of gastric parietal cells (secrete intrinsic factor + acid) Associations = B12 deficiency --> peripheral neuropathy, subacute combined degeneration of the cord, optic atrophy, dementia Investigations = IF Abs, parietal cell Abs (not specific) Management = Hydroxycobalamin B12 injections ```
48
``` Polycythaemia Pseudo vs primary vs secondary? Clinical features? Lab findings? Most common primary cause? Secondary causes? Primary management? ```
``` Pseudo = decrease in plasma volume Primary = rubra vera, myeloproliferative disorder Secondary = Other causes ``` Clinical = HTN, splenomegaly, thrombosis, pruritis, plethoric features, peptic ulceration, gout Lab - Raised RCC, Hb, haematocrit, viscosity, urate - In primary disease neut + platelet often raised 1 Cause = JAK2 mutation in 90% 2 Cause = - Appropriate EPO secretion as a response to hypoxia (physiological, cyanotic heart disease, respiratory disease, smokingg) - Inappropriate EPO secretion from kidney as a result of decreased O2 ddelivery to JGA (cysts, RAS, pyelonephrosis, transplant) - Inappropriate EPO secretion from tumour (renal carcinoma, hepatoma, uterine fibroid, cerebbellar hemangioblastoma) Management - aspirin and Venesection aiming PCV <0.45 - Cytotoxics e.g. hydroxycarbamidde
49
Beta thalassaemia trait Geneotype? Features?
b/- Hypochromic + microcytic anaemia. Microcytosis out of proportion to anaemia HbA2 raised
50
DVT Anticoagulant choice? Length of anticoagulation?
Anticoag: - Apixaban/rivaroxaban for suspected/confirmed - Severe renal impairment --> LMWH followed by VKA - Antiphospholipid syndrome --> LMWH followed by VKA Length - All at least 3 months - Provoked --> stop after 3 - Provoked + cancer --> 3-6 - Unprovoked --> 6 months
51
Tumour lysis syndrome Biochemical features? Prevention? Management?
Biochemistry - High: K, PO4, urate (from nucleic acid catabolism) - Low: Ca - AKI Prevention = IV fluids, prophylactic hypouricaemic agents (allopurinol, rasburicase) Management - Hyperkalaemia: cardiac monitoring, frequent K measurements, K binding drugs. Ca gluconate/insulin. ?RRT - Hypocalcaemia: avoid correction until phosphate lowered due to CaPO4 precipitation (unless severely symptomatic) - Hyperphosphataemia: aggressive IV hydration, PO4 binders, uric acid lowering therapies - Hyperuricaemia: rasburicase (allopurinol for prophylaxis ONLY) - AKI: may need RRT
52
Causes of isolated thrombocytopenia?
Artefact (clot in test tube) Immune thrombocytopenia Drugs (e.g. heparin, valproate, quinine, abciximab) Hypersplenism Gestational (NB HELLP syndrome causes low platelets)
53
Causes of microcytosis?
``` Fe deficiency Thalassaemia ACD (normocytic, normochromic is more common) Congenital sideroblastic anaemia Lead poisoning ```
54
Beta thalassaemia major Genotype? Age of presentation? Management?
-/- Normal at birth (b globin not needed for HbF). Onset over 1st year of life Management - Regular transfusions - Iron chelation to avoid overload (desferrioxamine)
55
G6PD deficiency Features? Blood film? Diagnostic test?
Features - Neonatal jaundice - Intravascular haemolysis precipitated by infection/drugs (anti-malarials, cipro, sulph drugs e.g. sulphonamides) - Gallstones common Blood film - Heinz bodies - Possibly bite/blister cells Diagnosis = G6PD film 3 months following episode (false -ve shortly after episode as RBCs with reduced activity have been destroyed)
56
Haemophilias Common clinical presentation? Coagulation test results? Affected clotting factors?
Presentation - Prolonged bleeding following trauma/surgery - muscular haematoma, haemarthrosis Coagulation = inc. APTT. Normal PT + bleeding time Clotting factors = VIII (A) or IX (B/Christmas disease) or XI (C)
57
Causes of massive splenomegaly? | Other causes?
``` Massive: Myelofibrosis CML Malaria Gaucher’s syndrome Visceral leishmaniasis ``` ``` Splenomegaly all causes: Myeloproliferative disorders Chronic haemolysis lymphoproliferative disorders (most lymphomas, CLL, hairy cell leukaemia) Portal HTN (cirrhosis, CCF) Bacterial infection (e.g. typhoid, brucella, TB) Viral infection (EBV, hepatitis) Tropical diseases (e.g. malaria) Collagen diseases Storage diseases ```
58
General features of MAHA?
Features of haemolysis - anaemia, high bili& LDH, low haptoglobin, reticulocytosis Blood film - schistocytes Possibly thrombocytopenia, cosumptive coagulopathy
59
Causes of macrocytosis associated with haematological disease & some features of each?
Myelodysplasia = Cytopenia, monocytosis, dysplastic features. Inc. myeloblasta Myeloma = paraprotein, high ESR, leukoerythroblastic blood picture Myeloprolifertive disorder = Polycythaemia, thrombocytopenia, myelofibrosis, CML Aplastic anaemia = pancytopenia, low reticulocytes, hypoplastic MB
60
Management of aplastic anaemia?
Stop possible drugs Supportive (e.g. RBC/platelet Tx, Abx, G-CSF) Immunosuppression Stimulate residual BM capacity - anabolic steroids BM transplantation
61
Cause of aplastic crisis in sickle cell disease/other congenital haemolytic anaemias?
Usually due to parvovirus B19 infection
62
Cause of pencil RBCs?
Fe deficiency anaemia
63
Causes of hyposplenism?
``` Splenectomy Sickle cell disease Coeliac disease Myeloproliferative disease associated with splenic infarcts Congenital aspleism ```
64
``` Methemoglobinaemia Definition? Common drug causes? Clinical features? Management? ```
Definition = conversion of Fe2+ in haemoglobin to Fe3+ after exposure to oxidising agent, causing inadequate oxygen transport Causes = local anaesthetic esp benzocaine, nitrates (esp. nitroglycerine, inhaled NO), Abx (esp. dapsone), other drugs (rasburicase) Features - low oxygen sats despite adequate PaO2 - Cyanosis at higher oxygen sats then would be expected - Brown discolouration of bloods which remains brown on exposure to air (unlike normal blood which turns red) Management - Methylene blue unless G6PD deficiency (may not work or cause haemolysis) - NADH methemoglobinemia reductase deficiency —> Ascorbiv acid
65
Management of primary thrombocytopenia?
Hydroxycarbamide (note teratogenicity) | Aspirin/anticoagulation if thrombosis
66
Natural anticoagulants? | Congenital thrombophilias?
Antithrombin Protein C - Vitamin K dependent. Inactivated factor V Protein S Factor V leiden (Protein C cannot bind) Protein S/C/Antithrombin deficiency (antithrombin most common) Prothrombin gene mutation
67
``` Burkitt's lymphoma Type of cancer? Genetic abnormality? Different types? Histology? ```
Type = B cell non-hodgkins lymphoma Genetics = translocation of MYC gene on chromosome 8 t(8;14) Types= - Endemic: Africa. tends to affect young boys on maxilla/mandible - Sporadic - Immunodeficiency associated: abdominal form is mos t common Histology = starry sky appearance (lymphocyte sheets interspersed with macrophages containing parts of apoptotic cells)
68
Causes of eosinophilia? | Consequence of chronic eosinophiplia?
Allergies Skin disorder: eczema, psoriasis, dermatitis herpetiformis Parasite infections: most (exceptions - malaria, threadworm) Myeloproliferative disorder: e.g. granulocytosis, CML Neoplasm: Hodgkin'd lymphoma, IL-5 secreting lymphoma Other conditions: sarcoid, polyarteritis nodosa, eosinophilic granuloma Prolonged eosinophilia --> endothelial/serous tissue damage via degranulation Mural thrombi. Endomyocardial fibrosis
69
Cause of target cells?
Normal cells volume with too large surface area: Liver disease (inc. membrane cholesterol content) Hyposplenism Fe deficiency Haemaglobinopathies
70
When to target INR 3-4.5?
Recurrent thrombosis, arterial disease, mechanical prosthetic valves
71
Thrombosis and the contraceptive pill
Oestrogen containing pill causes: - Inc. fibrinogen + vit K dependant clotting factors (2, 7, 9, 10) - Decrease antithrombin 4x greater risk of thromboembolism 8x if factor V leiden present
72
Paroxysmal nocturnal haemoglobinuria Definition & Cause? Clinical signs/symptoms? Diagnosis?
Acquired mainly intravascular haemolysis thought to be caused by lack of glycoprotein phosphotidylinositol —> increased sensitivity to complement lysis Features - haemolytic anaemia - any blood cells affected. May cause pancytopenia - haemoglobinuria classically in the morning - thrombosis Diagnosis = flow cytometry to detect CD59 & 55
73
Hodgkin’s lymphoma blood transfusion special requirement?
Irradiated blood for life
74
Causes of basophilic stippling?
Lead poisoning Thalassaemia Sideroblastic anaemia Myelodysplasia
75
Transfusion Associated Lung Injury Cause? Features? Management?
Cause = Possibly: host neutrophils activated --> vascular permeability Features - SOB + hypoxia within 6 hours of transfusion. Often febrile - Bl infiltrates on CXR Management - Supportive - Intubation/ventilation may be required -
76
Transfusions - Acute haemolytic reaction Cause? Features? Management?
Cause = ABO incompatible blood Features = fever, abdo pain, hypotension Management - STOP TRANSFUSION - Supportive care - confirm patient & blood - Send blood for Coombs test. Repeat cross match
77
Blood transfusions - anaphylaxis Associated condition? Features? Management?
Associated = IgA deficiency Features = hypotension, dyspnoea, wheezing, angioedema Management - STOP TRANSFUSION - Adrenaline - Supportive
78
Transfusion associated circulatory overload Features? Management?
Features = Respiratory distress, tachycardia, inc. BP, pulmonary oedema Management - Diuretics - Measure haematocrit. Dramatic elevation may require venesection to reduce stroke risk
79
What is associated with warfarin induced skin necrosis?
Protein C deficiency
80
Cold AIHA Usual Ab? Intra/extra vascular? Causes?
Usually IgM. Complement mediated. Usually intravascular. Causes - Infective (e.g. mycoplasm, EBV) - Neoplastic (lymphoma)
81
Leukaemoid reaction Definition? Causes? CML vs leukaemoid?
Presence of immature cells in peripheral blood Causes: severe infection/haemolysis/haemorrhage, BM infiltration CML vs leukaemoid - low vs high leucocyte alkaline phosphatase - leukaemoid: toxic granulation (Dhole bodies) in WBCs, neutrophil left shift (3 or fewer segments to nucleus)
82
Myelofibrosis Definition? Features? Lab findings?
Myeloproliferative disorder, possibly due to abnormal megakaryocyte hyperplasia --> PDGF release --> fibroblast stimulation Features - Most common = fatigue - Massive splenomegaly due to spleen haematopoeisis - Hypermatabolic symptoms Lab - Anaemia, poikilocytes, dry tap BM biopsy - Early disease: high WBC + platelets - Inc. cell turnover --> high urate + LDH
83
``` Chromosome translocations t(9;22) t(15;17) t(8;14) t(11;14) t(14;18) ```
t(9;22) / Philadelphia chromosome - >95% CML patients. Poor prognostic marker in AML - new BCR-ABL gene --> tyrosine kinase with Xs activity t(15;17) - Acute promyelocytic leukaemia - PML & RAR-alpha gene fusion t(8;14) - Burkitt's lymphoma - MYC oncogene translocated to Ig gene t(11;14) - Mantle cell lymphoma - Dysregulation of cyclin D1 t(14;18) - Follicular lymphoma - Inc. BCL-2 Memory aid: all lymphomas involve 14. - 8 looks like B = Burkitt's - 11 looks lime M = Mantle
84
Hereditary spherocytosis diagnosis?
Eosin-5-maleimide (EMA) binding test Testing may not be required in some cases: FHx, typical features (e.g. spherocytes, raised MCHC, inc. reticulocytes)
85
``` Infections and haematological malignancies EBV? HTLV-1? HIV-1? H. pylori? Malaria? ```
EBV = Hodgkin's & Burkitt's (& nasopharyngeal carcinoma) HTLV-1 = Adult T-cell leukaemia/lymphoma HIV-1 = High-grade B-cell lymphoma H. pylori = gastric lymphoma (MALT) Malaria = Burkitt's lymphoma
86
Warm autoimmune haemolytic anaemia Typical Ig? Extra or intravascular? Causes?
IgG Extravascular Causes = Autoimmune disease (e.g. SLE), neoplasia (e.g. lymphoma), drugs (e.g. methyldopa)