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K1s Path > Haematology > Flashcards

Haematology Flashcards

1
Q

How do platelets bind to exposed subendothelial cells/matrix and what does this trigger?

A
  • GlpIa to exposed collagen - GlpIb to Von Willebrand factor - Release of ADP and thromboxane A2 trigger platelet aggregation
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2
Q

What factors are involved in platelet aggregation?

A

GlpIIb/IIIa crosslink platelets via fibrinogen

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3
Q

Which arachidonic acid metabolites affect platelet aggregation?

A

Thromboxane A2 induces platelet aggregation Prostacyclin PGI2 inhibits platelet agggregation

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4
Q

What actions does thrombin have?

A
  • Cleaves Fibrinogen - Activates Platelets - Activates procofactors (FV and FVIII) - Activates zymogens (FVII, FXI and FXIII)
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5
Q

Describe the initiation phase?

A
  • Injury of vessels wall leads to contact between blood and subendothelial cells - Tissue factor (TF) is exposed and binds to FVIIa or FVII which is subsequently converted to FVIIa - The complex between TF and FVIIa activates FIX and FX - FXa binds to FVa on the cell surface
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6
Q

Describe the amplification phase?

A
  • The FXa/FVa complex converts small amounts of prothrombin into thrombin - The small amount of thrombin generated activates FVIII, FV, FXI and platelets locally. FXIa converts FIX to FIXa - Activated platelets bind FVa, FVIIIa and FIXa
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7
Q

Describe the propagation phase?

A
  • The FVIIIa/FIXa complex activates FX on the surfaces of activated platelets - FXa in association with FVa converts large amounts of prothrombin into thrombin creating a “thrombin burst”. - The “thrombin burst”leads to the formation of a stable fibrin clot.
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8
Q

What factor is activated to degrade fibrin?

A

Plasminogen is converted by tissue plasminogen activator (tPA) to plasmin which degrades fibrin.

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9
Q

What physiological anticoagulants are there?

A
  • Antithrombin III: main inhibitor of activated coagulation serine proteases. Also inactivates thrombin and activated factors X, IX, XI. ATIII activity is greatly accelerated (2000-fold) by heparin -Heparin co-factor II: complexes with thrombin inactivating it. Activity is amplified 1000-fold by heparin - Protein C + S: upon activation by thrombin in the presence of thrombomodulin, activated protein C inactivates VIIIa and Va, thus reducing the rate of thrombin generation. Protein S is a cofactor - Tissue factor pathway inhibitor: binds to Xa and TF:VIIa complex, inhibiting their proteloytic activity
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10
Q

Which substances mediate vasoconstriction in haemostasis?

A
  • adrenaline - ADP - kinins - thromboaxanes
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11
Q

Which coagulation factors are dependent on vitamin K for their normal function?

A

II, VII, IX, X, protein C and protein S

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12
Q

How does clopidogrel inhibit platelet aggregation?

A

Clopidogrel is a specifc, non-competive inhibitor of ADP- induced platelet aggregation, irreversibly inhibiting the binding of ADP to its platelet membrane receptors. Ultimately it inhibits the activation of the GPIIb/IIIa receptor, its binding to fibrinogen and further platelet aggregation.

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13
Q

What are the common causes of thrombocytopenia?

A

Immune-mediated Idiopathic Drug-induced Connective tissue disease Lymphoproliferative disease Sarcoidosis Non-immune mediated DIC Microangiopathic hemolytic anemia

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14
Q

What is the treatment for ITP?

A

>50,000 - Nothing 20-50,000 - Not bleeding: None - Bleeding : Steroids + IVIG <20,000 - Not bleeding: Steroids - Bleeding : Steroids, IVIG, Hospitalization

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15
Q

What are the clinical features of haemophilia?

A

X-linked congenital deficiency - Factor 8 (A) or 9 (B) Bleeding – Haematoma, joint etc. Prolonged aPTT but normal PT. Clotting factor replacement-Life long.

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16
Q

What are the clinical features of von Willebrand Disease?

A

Inheritance - autosomal dominant Incidence - 1/10,000 Clinical features - mucocutaneous bleeding Classification: Type 1 - Partial quantitative deficiency Type 2 - Qualitative deficiency Type 3 - Total quantitative deficiency

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17
Q

What are the components of Virchow’s triad?

A

Vessel wall, blood, flow.

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18
Q

What inherited thrombophilia risk factors are there?

A
  • Anticoagulant deficiency (All rare): Protein C (0.3%), Protein S, Antithrombin (<0.2%) - Procoagulant excess (common): Factor VIII (10% of population), Factor II (2%), Fibrinogen - Additional factors: Factor V Leiden (5% caucasians), Lupus anticoagulant, Prothrombin G20210A
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19
Q

What is Lupus anticoagulant?

A

An immunoglobulin that binds to phospholipids and proteins associated with the cell membrane and increases the risk of thrombosis.

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20
Q

What acquired thrombophilia risk factors are there?

A

Age, obesity, previous DVT or PE, immobilisation, major surgery, long distance travel, malignancy (esp. pancreatic), pregnancy, COCP, HRT, antiphospholipid syndrome, polycythaemia, thrombocythaemia

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21
Q

What anticoagulant molecules are normally expressed by blood vessel walls?

A
  • Thrombomodulin: Directs thrombin to activate protein C - Endothelial protein C receptor: Presents PC to Thrombomodulin - Tissue factor pathway inhibitor: Inhibits Tissue factor - Prostacyclin (PGI2): Inhibits platelet activation - Nitirc Oxide: Inhibits platelet activation
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22
Q

What is used as DVT prophylaxis?

A

Chemical: low molecular weight heparin e.g. Tinzaparin, Clexane Mechanical: TED stockings or intermittent compression devices

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23
Q

What is the treatment for a DVT/PE?

A

Immediate: Low molecular weight heparin until 2 days therapeutic INR Ongoing: warfarin for 3-6 months, started simultaneously In cancer patients continue LMWH not warfarin THrombolysis reserved for life threatening PE or limb threatening DVT

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24
Q

How does heparin work, how is it administered and what long-term side effects are there?

A

Potentates antithrombin III which inactivates thrombin and factors 9, 10, 11 LMWH: SC OD, no monitoring (anti-Xa assay) except in renal failure and late pregnancy Unfractionated: IV infusion, monitor APTT Side effects: heparin induced thrombocytopenia and osteoporosis (more common with UFH)

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25
Q

What is the treatment for heparin overdose?

A

Protamine sulphate

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26
Q

How does warfarin work?

A

Inhibits regeneration of active vitamin K (via reductase enzymes) thus inhibits synthesis of factors 2, 7, 9, 10 and proteins C, S and Z

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27
Q

How does Rivaroxaban work?

A

It is an orally active direct factor Xa inhibitor

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28
Q

How does Dabigatran work?

A

Direct anti-thrombin inhibitor

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29
Q

What is factor V Leiden?

A

A polymorphic mutation which makes Factor V resistant to protein C. Affects 5% of white population

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30
Q

What are the consequences of red cell antibodies (e.g. anti-RhD) in pregnancy?

A

Only IgG antibodies can cross the placenta. If the maternal antibody level is high, they can destroy foetal red cells causing the foetus to become anaemic and jaundiced = Haemolytic Disease of the Newborn. Rh D = most important cause of severe HDN, also only one with preventative treatment. Other blood groups can cause HDN e.g.: anti-Rh C, anti-K. IgG ABO antibodies can also cause HDN but this is usually not severe.

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31
Q

How is Haemolytic Disease of the Newborn prevented in a RhD negative women carrying an RhD positive foetus?

A

Giving her IM anti-D Ig at times when she is at risk of a feto-maternal haemorrhage; - routine antenatal prophylaxis at 28 and 34 weeks has been shown to significantly reduce the sensitisation, due to ‘silent’ bleeds in the 3rd trimester - during pregnancy if sensitising event occurs: abortion, miscarriage requiring medical/surgical evacuation, abdo trauma, external cephalic version, amniocentesis, stillbirth - at delivery if the baby is RhD positive Anti-D Ig only works if the mother is not already sensitised

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32
Q

What is a Kleihauer test?

A

A blood test used to measure the amount of foetal haemoglobin transferred from a foetus to a mother’s bloodstream. It is usually performed on Rhesus-negative mothers to determine the required dose of Rho(D) immune globulin to inhibit formation of Rh antibodies in the mother and prevent Rh disease in future Rh-positive children.

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33
Q

What are the two main causes of an immediate severe blood transfusion reaction?

A

1) Wrong (ABO incompatible) blood 2) Bacterial infection of the blood

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34
Q

What immediate adverse reactions to a blood transfusion can occur?

A

Immune: - ‘Wrong blood’ ABO incompatibility - Febrile non-haemolytic - Allergic / anaphylaxis - Transfusion related acute lung injury Non-immune: - Bacterial infection - Transfusion associated cardiac overload

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35
Q

What delayed adverse reactions to a blood transfusion can occur?

A

Immune: - Delayed haemolytic transfusion reaction - Port-transfusion purpura - Transplant -associated GVHD Non-Immune: - Viral infections + other - Iron overload

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36
Q

What causes febrile non-haemolytic transfusion reactions?

A

White cell antibodies in the patient which react with white cells in the donor’s blood, causing fever and rigors. This is less common since leucodepletion of all donor blood.

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37
Q

What causes transfusion related acute lung injury?

A

Very rare. Occurs if the donor’s plasma contains potent white cell antibodies incompatible with the recipient’s white cells. Transfusion may cause a severe reaction characterised by chills, fever, a dry cough and breathlessness with cardiac failure. TACO more likely

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38
Q

What causes a delayed haemolytic transfusion reaction?

A

Many occur in patients who have antibodies (other than ABO), if specially selected blood is not given. Usually manifested by fever days to weeks after a transfusion, accompanied by a falling haemoglobin, and jaundice or haemoglobinuria.

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39
Q

What translation forms the RUNX1-RUNX1T1 fusion protein and what disease is it associated with?

A

t(8;21) = one of the most frequent karyotypic abnormalities in acute myeloid leukaemia (esp M2 subtype)

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40
Q

What is the two-hit model of AML pathogenesis?

A

That two different classes of mutation are needed; - Class I mutations confer proliferative and/or survival advantage, but do not affect differentiation e.g. tyrosine kinase mutations - Class II mutations serve primarily to impair haematopoietic differentiation and subsequent apoptosis

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41
Q

What are the common presenting features of chronic myeloid leukaemia?

A

• M:F 1.4:1 • 40-60 years • Weight loss, lethargy, night sweats • Splenomegaly (often massive) • Features of anaemia • Bruising/bleeding • Gout 100% BCR:ABL fusion gene >95% of cases show Philadelphia chromosome

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42
Q

What are the phases of CML?

A

Chronic phase 20% blasts

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43
Q

What is the most sensitive method of assessing residual or relapsed CML?

A

Molecular RT-PCR followed by cytogenetic analysis then haematological response.

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44
Q

What is the first line treatment for CML?

A

Imatinib - BCR-ABL kinase inhibitor - first line therapy for CML in the chronic phase. If blast crisis (or resistant to all TK inhibitors) - consider allogeneic stem cell transplant

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45
Q

What tyrosine kinase inhibitors are available for CML treatment?

A

Imatinib - first line Dasatanib Nilotinib

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46
Q

What disease is associated with t(15;17)?

A

Acute promyelocytic leukaemia

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47
Q

Which chromosomes are commonly duplicated or deleted in AML?

A

Duplicated: 8 and/or 21 Loss or deletion: 5/5q and/or 7/7q

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48
Q

What risk factors are there for AML?

A

Unknown aetiology Familial or constitutional predisposition Irradiation Anticancer drugs Cigarette smoking Benzene exposure Down’s syndrome

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49
Q

What are the clinical features of AML?

A
  • Bone marrow failure: Anaemia, Neutropenia, Thrombocytopenia - Local infiltration: Splenomegaly Hepatomegaly Gum infiltration (if monocytic) Lymphadenopathy (only occasionally) Skin, CNS or other sites
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50
Q

How is AML often diagnosed?

A

Peripheral blood film - circulating blasts - Auer rods

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51
Q

What are the principles of treatment for AML?

A
  • Supportive care to correct the effects of inadequate bone marrow function (red cells, platelets, antibiotics) - Combination chemotherapy - Possibly targeted molecular therapy (strongly indicated for acute promyelocytic leukaemia) - Possibly immunotherapy - Possibly haemopoietic stem cell transplantation
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52
Q

What are the clinical features of ALL?

A
  • Peak incidence in childhood - Bone marrow failure: Anaemia, Neutropenia, Thrombocytopenia - Local infiltration: Lymphadenopathy (± thymic enlargement) Splenomegaly Hepatomegaly Testes, CNS, kidneys or other sites Bone (causing pain)
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53
Q

What cytogenetic factors are good / bad prognostic indicators for ALL?

A

Hyperdiploidy - good prognosis Hypodiploidy - poor prognosis Philadelphia chromosome - poor prognosis

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54
Q

Which is more common, T- or B-lineage ALL?

A

B-lineage = 85% T-lineage = 15%

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55
Q

What are the general principles of treatment for ALL?

A

Specific therapy: - systemic chemotherapy (girls 2 yrs, boys 3 yrs) - CNS directed therapy Supportive care: - blood products - antibiotics - general medical care

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56
Q

What is the cause of an iron deficiency anaemia and what lab findings would there be?

A

Bleeding until proven otherwise - GI tract - Urinary tract Laboratory findings: - Reduced ferritin and transferrin saturation - Raised TIBC

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57
Q

What are the cancer-associated anaemias?

A
  • Iron deficiency - Anaemia of inflammation - Leucoerythroblastic anaemia - Acquired haemolytic anaemia > Immune mediated > Fragmentation (microangiopathic) mediated Cancer may cause polycythaemia e.g. renal cell cancer
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58
Q

What is the pathogenesis of anaemia of inflammation and what would the laboratory findings be?

A
  • Adequate iron stores but these are not released to the developing erythroid precursors - Iron is sequestered and retained in macrophages > Normo- or microcytic anaemia > Normal or high ferritin > Normal or low iron and TIBC
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59
Q

How and why is iron sequestered in macrophages in anaemia of inflammation?

A

Hepcidin binds iron as a defence mechanism against bacterial infection

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60
Q

What are the features of leucoerythroblastic anaemia?

A
  • normocytic normochromic anaemia with numerous poikilocytes - normoblasts (nucleated red cells) - low-grade reticulocytosis (2-5%) - circulating immature white cells, generally myelocytes and promyelocytes - thrombocytopaenia is more common than thrombocythaemia
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61
Q

What are the causes of a leucoerythroblastic anaemia?

A

Bone marrow infiltration - Cancer: haemopoietic, non-haemopoietic - Severe infection: miliary TB, severe fungal infection - Myelofibrosis

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62
Q

What are the common lab features of haemolysis?

A
  • anaemia (though may be compensated) - reticulocytosis - raised Bilirubin (unconjugated) - raised LDH - reduced haptoglobins
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63
Q

What test is used to distinguish between types of acquired haemolytic anaemia?

A

Direct Antiglobulin (DAT or Coombs test) Distinguishes between immune (+) or non-imune (-)

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64
Q

What are the causes of a non-immune acquired haemolytic anaemia?

A

Infection (malaria) Micro-angiopathic Paroxysmal nocturnal haemoglobinuria

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65
Q

What features are there on a blood film with microangiopathic haemolytic anaemia?

A

Red cell fragments Thrombocytopenia Schistocytes

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66
Q

What are the causes of a microangiopathic haemolytic anaemia?

A

Mechanical RBC destruction by fibrin mesh in vessels - haemolytic uraemic syndrome - thrombotic thrombocytopenic purpura - DIC (adenocarcinomas - low grade DIC) - pre-eclampsia

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67
Q

What is paroxysmal nocturnal haemoglobinuria?

A

Marchiafava-Micheli syndrome: a rare, acquired loss of protective surface GPI markers on RBCs leading to complement-induced intravascular haemolytic anaemia, red urine and thrombosis.

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68
Q

What are the causes of a neutrophilia?

A
  • infection - corticosteroids - underlying neoplasia - tissue inflammation (e.g.colitis, pancreatitis) - myeloproliferative/ leukaemic disorders
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69
Q

Which infections characteristically do not produce a neutrophilia?

A
  • brucella - typhoid - many viral infections
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70
Q

What are the causes of a reactive eosinophilia?

A
  • parasitic infestation - allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia. - Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia) - Drugs (reaction erythema mutiforme)
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71
Q

What are the causes of a monocytosis?

A

Rare but seen in certain chronic infections and primary haematological disorders: - TB, brucella, typhoid - Viral; CMV, varicella zoster - sarcoidosis - chronic myelomonocytic leukaemia (MDS)

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72
Q

An ESR >100 mm/hr is suggestive of what?

A
  • Myeloma - Systemic autoimmune disease - Active TB
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73
Q

What is plasma cell myeloma?

A

A neoplastic proliferation of bone marrow plasma cells associated with a monoclonal protein in serum and/or urine = 1% of all cancers, average survival 3-5 years

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74
Q

What are the clinical features of myeloma?

A
  • asymptomatic - Calcium high - Renal failure (plus amyloidosis and nephrotic syndrome) - Anaemia (and pancytopenia) - Bone pain, lytic lesions and fractures - hyperviscosity syndrome
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75
Q

What staging system is used for plasma cell myeloma?

A

Durie-Salmon, I-III Also International Staging System (ISS) based on beta-2-microglobulin

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76
Q

When is the ESR normal in a patient with myeloma?

A

When the myeloma produces only free light chains and no serum paraprotein or is non-secretory (3%)

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77
Q

What are the general aspects of treatment for myeloma?

A

• Hypercalcaemia: rehydration, intravenous infusion of a bisphosphonate, e.g. pamidronate. • Renal failure: correct dehydration, treat hypercalcaemia, dialysis if required • Anaemia: usually improves when the disease responds. Blood transfusions may be needed • Bone disease: local radiotherapy for pain, long-term bisphosphonate. • Infection: treat promptly and vigorously, influenza vaccine annually.

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78
Q

What are the specific treatment options for myeloma?

A

• Chemotherapy often combined with steroids. e.g. CTD (cyclophosphamide, thalidomide and dexamethasone), melphalan and prednisolone. • Bortezomib is used as second-line therapy and lenalidomide is used as third-line therapy. • Radiotherapy for local areas of disease, e.g. for pain or cord compression • High-dose therapy with stem cell support in younger patients (autologous or allogeneic)

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79
Q

What are myelodysplastic syndromes?

A

A heterogenous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells characterised by: - peripheral cytopenia - qualitative abnormalities of cell maturation - risk of AML transformation Typically seen in elderly, symptoms develop over weeks & months

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80
Q

What is Pelger-Huet anomaly?

A

Hyposegmented neutrophil - bilobed nucleus Pseudo-Pelger-Huet anomaly can be seen in MDS

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81
Q

What abnormal blood and bone marrow morphological features can be seen in MDS?

A
  • Hypercellular bone marrow (normal < 5% blasts) - Defective cells > WBCs: Pseudo-Pelger-Huet anomaly and dysganulopoieses of neutrophils, myelokathexis > Dyserythropoiesis of RBCs e.g. ring sideroblasts > Dysplastic megakaryocytes e.g. micro-megakaryocytes
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82
Q

What is myelokathexis?

A

Retention of neutrophils in the bone marrow - often have hypersegmented nuclei

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83
Q

What stain is used to show ringed sideroblasts?

A

Prussian blue stain

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84
Q

How is prognosis worked out in MDS?

A

International prognostic scoring system, depends on BM blast %, karyotype, degree of cytopenia. Mortality ‘rule’: 1/3 die from infection, 1/3 bleeding and 1/3 acute leukaemia

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85
Q

What is the general treatment for MDS?

A

Supportive care: - Blood product support - Antimicrobial therapy - Growth factors (Epo, G-CSF) Biological Modifiers: - Immunosuppressive therapy - Azacytidine - Lenalidomide Chemotherapy: similar to AML Allogenic SCT

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86
Q

What are the blood and bone marrow features of refractory anaemia? (RA)

A

Blood: anaemia, no blasts BM: erythroid dysplasia with <5% blasts

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87
Q

What are the blood and bone marrow features of refractory anaemia with ringed sideroblasts? (RA +RS)

A

Blood: anaemia, no blasts BM: erythroid dysplasia with >15% ringed sideroblasts

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88
Q

What are the blood and bone marrow features of refractory cytopenia with multi-lineage dysplasia? (RCMD)

A

Blood: Bicytopenia or pancytopenia BM: Dysplasia in >10% cells in 2 or more cell lines

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89
Q

What are the blood and bone marrow features of refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts? (RCMD +RS)

A

Blood: Bicytopenia or pancytopenia BM: Dysplasia in >10% cells in 2 or more cell lines and >15% ringed sideroblasts

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90
Q

What are the blood and bone marrow features of refractory anaemia with excess blasts-1? (RAEB I)

A

Blood: Cytopenias, <5% blasts, no Auer rods BM: Dysplasias, 5-9% blasts

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91
Q

What are the blood and bone marrow features of refractory anaemia with excess blasts-2? (RAEB II)

A

Blood: Cytopenias or 5-19% blasts or Auer rods BM: Dysplasias, 10-19% blasts or Auer rods

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92
Q

What are the blood and bone marrow features of MDS with 5q deletion?

A

Blood: Anaemia, normal or increased platelets BM: Megakaryocytes with hypolobulated nuclei and <5% blasts

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93
Q

What are the blood and bone marrow features of Myelodysplasia Syndrome Unclassified?

A

Blood: Complex - cytopenias, no blasts, no Auer rods BM: Complex - myeloid or megakaryocytic dysplasia, <5% blasts

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94
Q

Blood: anaemia, no blasts BM: erythroid dysplasia with <5% blasts

A

refractory anaemia (RA)

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95
Q

Blood: anaemia, no blasts BM: erythroid dysplasia with >15% ringed sideroblasts

A

refractory anaemia with ringed sideroblasts (RA +RS)

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96
Q

Blood: Bicytopenia or pancytopenia BM: Dysplasia in >10% cells in 2 or more cell lines

A

refractory cytopenia with multi-lineage dysplasia (RCMD)

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97
Q

Blood: Bicytopenia or pancytopenia BM: Dysplasia in >10% cells in 2 or more cell lines and >15% ringed sideroblasts

A

refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD +RS)

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98
Q

Blood: Cytopenias, <5% blasts, no Auer rods BM: Dysplasias, 5-9% blasts

A

refractory anaemia with excess blasts-1 (RAEB I)

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99
Q

Blood: Cytopenias or 5-19% blasts or Auer rods BM: Dysplasias, 10-19% blasts or Auer rods

A

refractory anaemia with excess blasts-2 (RAEB II)

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100
Q

Blood: Anaemia, normal or increased platelets BM: Megakaryocytes with hypolobulated nuclei and <5% blasts

A

MDS with 5q deletion

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101
Q

Blood: Complex - cytopenias, no blasts, no Auer rods BM: Complex - myeloid or megakaryocytic dysplasia, <5% blasts

A

Myelodysplasia Syndrome Unclassified

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102
Q

What inherited bone marrow failure syndromes are there?

A

Fanconi anaemia Dyskeratosis congenita Schwachman-Diamond syndrome Diamond-Blackfan syndrome

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103
Q

What are the acquired causes of aplastic anaemia?

A

Idiopathic (70%) Marrow infiltration: > Haematological (leukaemia, lymphoma, myelofibrosis) > Non-haematological (Solid tumours) Radiation Drugs Chemicals (benzene) Autoimmune (SLE) Infection (Parvovirus, Viral hepatitis)

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104
Q

What is the general management of aplastic anaemia?

A

> Supportive - transfusions, antibiotics, iron chelation > Drugs to promote marrow recovery - growth factors, oxymetholone > Immunosuppressants (idiopathic AA ~70%) > Stem cell transplant

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105
Q

What is aplastic anaemia and how is it classified?

A

Aplastic anaemia is defined as pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulin. It is classified as non-severe, severe, or very severe on the basis of the degree of peripheral-blood pancytopenia

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106
Q

What is Fanconi anaemia?

A

Commonest form of inherited (AR or X) aplastic anaemia. Multiple genes responsible: normally contribute to genomic stability. Blood counts and marrow cellularity often normal until 5-10 yrs then pancytopenia develops, 10% progress to AML. Skeletal abnormalities (thumbs), renal malformations, microcephaly, hypogonadism, short stature, skin pigmentation.

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107
Q

What is dyskeratosis congenita?

A

X-linked disorder characterised by marrow failure, cancer predisposition and somatic abnormalities. Classic triad: skin pigmentation, nail dystrophy, oral leukoplakia

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108
Q

What is Schwachman-Diamond syndrome?

A

A rare AR congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction (neutropenia +/- others), skeletal abnormalities, and short stature.

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109
Q

What is Diamond-Blackfan Syndrome?

A

A congenital hypoplastic anaemia that usually presents in infancy with pure red-cell aplasia, normal WCC and platelets. Often other congenital anomalies.

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110
Q

What are the blood count changes in pregnancy?

A

Mild anaemia: RCM 120-130%, plasma volume 150% = net dilution Macrocytosis: MCV rises 5-10 fl Neutrophilia Thrombocytopenia: increased platelet size

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111
Q

What supplements are recommended during pregnancy?

A

Iron: 3x increase in requirements, need extra 800mg, RDA 30mg. No routine supplementation in UK Folate: additional 200mcg/day required WHO recommends 60mg Fe +400mcg folic acid daily during pregnancy

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112
Q

What possible effects are there of iron deficiency during pregnancy?

A

Preterm delivery Low birth weight, Possibly placental abruption, Increased peripartum blood loss,

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113
Q

What happens to the platelet count during pregnancy?

A

Decrease ~10% - can drop into thrombocytopenic range. Combination of haemodilution and increased platelet activation and clearance.

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114
Q

What are the causes of thrombocytopenia in pregnancy?

A
  • Physiological - Pre-eclampsia - Immune thrombocytopenia (ITP) - Microangiopathic syndromes - All other causes: bone marrow failure, leukaemia, hypersplenism, DIC etc.
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115
Q

What is the relationship between pre-eclampsia and thrombocytopenia?

A

50% get thrombocytopenia: proportionate to severity. Probably due to increased activation and consumption. Usually remits following delivery.

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116
Q

What are the treatment options for immune thrombocytopenia in pregnancy?

A

When symptomatic or count <20 IV immunoglobulin Steroids etc. (Anti-D where Rh D +ve) Baby may be affected for up to 5 days post delivery (IVIG if low)

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117
Q

What are the main coagulation changes in pregnancy?

A

Increase in vWF (x3-5), fibrinogen (x2) and factors 7, 8, 10 50% decrease in protein S Also increase in plasminogen activator inhibitors 1+2 Net effect = procoagulant state

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118
Q

When are pregnant women at risk of thromboembolism?

A

From the very beginning of pregnancy until well into postpartum period

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119
Q

What factors increase the risk of thrombosis in pregnancy?

A

Bed rest Obesity Pre-eclampsia Operative delivery Previous thrombosis/thrombophilia Age Parity Multiple pregnancy IVF: ovarian hyperstimulation

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120
Q

How should pregnant women with VTE risk factors be managed?

A
  • Prophylactic heparin +TED stockings > Either throughout pregnancy > Or in peri-post- partum period > Highest risk get adjusted dose LMWH heparin - Mobilise early - Maintain hydration
121
Q

How should pregnant women with a VTE be managed?

A
  • LMWH as for non-pregnant - Do not convert to warfarin (teratogenic) - After 1st trimester monitor anti Xa - Stop for labour or planned delivery, esp. for epidural
122
Q

What is the definition of post partum haemorrhage and what are the major factors?

A

>500 ml blood loss - uterine atony - trauma haematological factors minor except - dilutional coagulopathy after resuscitation - DIC in abruption, amniotic fluid embolism etc

123
Q

What conditions can precipitate decompensation to DIC in pregnancy?

A

Amniotic fluid embolism Abruptio placentae Retained dead fetus Pre-eclampsia (severe) Sepsis

124
Q

What possible consequences of haemolytic anaemia are there?

A

Anaemia(+/-) - Erythroid hyperplasia with increased rate of RBC production and circulating reticulocytes - Increased folate demand - Susceptibility to effect of parvovirus B19 - Increased risk of gallstones, iron overload, osteoporosis

125
Q

What are the main inherited causes of haemolytic anaemia?

A
  • Membrane defects: hereditary spherocytosis, hereditary elliptocytosis - Enzyme defects: G6PD deficiency, pyruvate kinase deficiency - Haemoglobinopathies: sickle cell disease, thalassaemias
126
Q

What is hereditary spherocytosis?

A

75% AD cause of extravascular haemolysis Spectrin or ankyrin deficiency Suseptible to parvovirus B19 and gallstones Diagnosed by blood film and osmotic fragility test Treat with splenectomy and folic acid

127
Q

What is hereditary elliptocytosis?

A

AD spectrin mutations Broad range in severity

128
Q

What does G6PD do?

A

Glucose-6-phosphate dehydrogenase catalyses first step in pentose phosphate pathway - generates NADPH required to maintain intracellular glutathione (GSH)

129
Q

Where is G6PD deficiency prevalent?

A

In areas of malarial endemicity i.e.. African, Mediterranean and Middle Eastern populations

130
Q

What are the clinical features of G6PD deficiency?

A

X-linked RBC enzyme deficiency Neonatal jaundice Acute haemolytic attacks with bite cells, Heinz bodies, dark urine Attacks precipitated by oxidants Chronic haemolytic anaemia (rare)

131
Q

What agents may provoke haemolysis in G6PD deficiency?

A
  • Anti-malarials: Primaquine - Antibiotics: Sulphonamides, Ciprofloxacin, Nitrofurantoin - Other drugs: Dapsone, Vitamin k, Aspirin - Fava beans - Mothballs
132
Q

For which haemolytic anaemias is there substantial benefit from splenectomy?

A

PK deficiency and some other enzymopathies Hereditary spherocytosis Severe elliptocytosis/pyropoikilocytosis Thalassaemia syndromes Immune haemolytic anaemia

133
Q

What are the indications/criteria for splenectomy as a treatment for haemolytic anaemia?

A

Transfusion dependence Growth delay Physical limitation Hb < 8g/dl Hypersplenism Age not < 3 yrs but before 10 yrs to maximise prepubertal growth

134
Q

What is pyruvate kinase deficiency?

A

Majority autosomal recessive Severe neonatal jaundice, splenomegaly, haemolytic anaemia Most do not require treatment but may include transfusion or splenectomy

135
Q

What is the incidence of lymphoma?

A

1 new case per 5000 each year Non-Hodgkin’s Lymphomas 80% Hodgkin Lymphoma 20%

136
Q

What risk factors are there for lymphoma?

A
  • Majority of case no identifiable risk factors - Constant antigenic stimulation - Infection(viral infection of cells) - Immunosupression (HIV and immunosuppresants)
137
Q

What three inherent characteristics of the immune system make it susceptible to malignant change?

A

Rapid cell proliferation in immune response > Proliferating cells risk DNA replication error Dependent on apoptosis (90% of normal cells die!) > Apoptosis is “switched off” in germinal centre DNA molecules are cut and rejoined plus undergo deliberate point mutations > Potential for rejoining errors and new point mutations

138
Q

What is the epidemiology of Hodgkin’s Lymphoma?

A

M>F 20-29 peak, second smaller peak >60 EBV-associated

139
Q

What is the classical clinical presentation of Hodgkin’s Lymphoma?

A
  • Asymmetrical painless lymphadenopathy =/- obstructive/mass effect symptoms +/- Constitutional (B) symptoms; fever, night sweats, weight loss, pruritis - Rarely alcohol induced pain - Pel-Ebstein fever: cyclical 1-2wk in minority - reed-sternberg cell
140
Q

What subtypes of Hodgkin’s Lymphoma are there?

A

Nodular sclerosing 80% Mixed cellularity 17% Lymphocyte rich (rare) Lymphocyte depleted (rare, poor prog) Nodular Lymphocyte predominant 5% (not classical HL)

141
Q

How is Hodgkin’s Lymphoma staged?

A

I - one group of nodes (includes spleen) II - >1 group of nodes same side of the diaphragm III - nodes above and below the diaphragm IV - extra nodal spread (liver, BM) Plus A if no constitutional symptoms, B if there are any Same staging system used for NHL too.

142
Q

What is the commonest chemotherapy regime used to treat Hodgkin’s Lymphoma?

A

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine (DITC) - given at 4-weekly intervals - preserves fertility - can cause pulmonary fibrosis and cardiomyopathy later

143
Q

What is non-Hodgkin’s lymphoma?

A

All lymphomas other than Hodgkin’s, ~ 40 different subtypes Can be classified as; - mature or immature - high or low grade - B or T cell lineage

144
Q

What are the clinical features of non-Hodgkin’s lymphoma?

A

Presentation varies significantly from subtype to subtype Similarities: painless lymphadenopathy, often involving multiple sites, constitutional symptoms, no pain after alcohol Staging as per Hodgkin’s

145
Q

Examples of indolent, low grade non-Hodgkin’s lymphomas?

A
  • Follicular lymphoma - Small lymphocytic/CLL - Mucosa associated (MALT)
146
Q

Examples of aggressive, high grade non-Hodgkin’s lymphomas?

A

Aggressive - Diffuse Large B cell - Mantle cell Very aggressive - Burkitt Lymphoma - T or B cell Lymphoblastic leukaemia/lymphoma

147
Q

What is the commonest subtype of non-Hodgkin’s lymphoma and what is a standard treatment regime?

A

Diffuse large B cell lymphoma 30-40% of all NHL 6-8 cycles of R-CHOP - Rituximab - Cyclophosphamide - Adriamycin (Hydroxydaunomycin) - Vincristine (Oncovin) - Prednisolone

148
Q

How is prognosis calculated for diffuse large B cell lymphoma?

A

International Prognostic Index, a point for each of; - Age > 60y - serum LDH > normal - performance status 2-4 - stage III or IV - more than one extranodal site

149
Q

What is the commonest indolent non-Hodgkin’s lymphoma and what is it associated with?

A

Follicular lymphoma ~35% of NHL Associated with t(14;18) which results in over-expression of bcl2 an anti-apoptosis protein Incurable, median survival 12-15 years

150
Q

What is a MALT lymphoma?

A

A Marginal zone NHL involving extranodal lymphoid tissue due to chronic antigen stimulation; - Sjogrens syndrome ; parotid lymphoma - H.Pylori ; Gastric MALT lymphoma Can be pathogen dependent so antibiotics cure

151
Q

What sections can the lymphoreticular system be classified into?

A
  • Generative: Bone marrow and thymus - Reactive: Lymph nodes and spleen - Acquired: Extranodal lymphoid tissue
152
Q

What is the definition of a lymphoma?

A

Neoplastic proliferation of lymphoid cells forming discrete tissue masses. Arise in and involve lymphoid tissues (including acquired lymphoid tissue).

153
Q

What immunohistochemistry and translocations identify a folicular lymphoma?

A
  • CD10, bcl-6 (GC) and bcl-2 - 14;18 translocation involving bcl-2 gene
154
Q

What immunohistochemical profile does small lymphocytic lymphoma/CLL have?

A

CD5, CD23 +

155
Q

What immunohistochemical profile and translocations does mantle cell lymphoma have?

A
  • CD5, cyclin D1 over expression - 11;14 translocation
156
Q

What are the features and associations of Burkitt’s lymphoma?

A
  • Jaw or abdominal mass children/young adults - EBV associated - “starry-sky” appearance on histology - CD10, bcl6 (GC) - C-myc translocation (8:14, 2:8, 8;22)
157
Q

Which has a better prognosis, germinal center or post-germinal center diffuse large B cell lymphoma?

A

Germinal center phenotype

158
Q

What type of lymphoma is associated with HTLV-1?

A

Human T-lymphotropic virus type I causes adult T cell leukaemia and lymphoma

159
Q

What translocation and protein expression is associated with anaplastic large cell lymphoma?

A

2;5 translocation Alk-1 protein expression CD30 +, T cell or null phenotype

160
Q

What is the histological picture of Hodgkin’s lymphoma?

A

Sclerosis, mixed cell population in which scattered Reed-Sternberg and Hodgkin cells with eosinophils

161
Q

What is chronic lymphocytic leukaemia and how does it normally present?

A

Progressive accumulation of malignant mature B lymphocytes in the blood, bone marrow and lymphoid tissues. Commonest leukaemia in western world. 70-80% incidental diagnosis, majority over 60. Bone marrow failure, recurrent sinopulomary infection (hypogamaglobulinaemia) and auto-immune phenomena (AIHA, ITP)

162
Q

What peripheral blood and bone marrow findings are there in chronic lymphocytic leukaemia?

A
  • Lymphocytosis between 5 and 300 x 10^9/L - Smear cells - Normocytic normochromic anaemia - Thrombocytopenia Bone marrow: lymphocytic replacement of normal marrow elements
163
Q

What does immunophenotyping usually reveal in chronic lymphocytic leukaemia?

A

CD5 CD19 CD20 CD23 CD79a Surface IgM

164
Q

What staging systems are used for CLL?

A

Rai staging (0-IV) or Binet staging (A-C)

165
Q

What chromosomal abnormalities detected via FISH are prognostic for CLL?

A

Deletion of 13q - good prognosis, better than normal Trisomy 12 - good Deletion of 11q (ATM) - poor Deletion of 17p (TP53) - very poor

166
Q

What carries a better prognostic value, mutated or unmutated IgH gene in CLL?

A

Unmutated worse prognosis

167
Q

What is Richter’s syndrome?

A

Aka Richter’s transformation, is a complication of CLL and hairy cell leukaemia in which the leukaemia changes into a fast-growing diffuse large B cell lymphoma or Hodgkin’s lymphoma. Happens to 5-10% of CLL patients. Treat with CHOP-R

168
Q

What are the indications for treatment of CLL?

A
  • Progressive lymphocytosis >50% increase over 2 months or lymphocyte doubling time <6 months - Progressive marrow failure - Massive or progressive lymphadenopathy/splenomegaly - Systemic (B) symptoms - Autoimmune cytopenias (treat with steroids or Rituximab)
169
Q

What antibodies are sometimes used as therapies for CLL and when?

A

Alemtuzemab/Campath: anti-CD52 > 1st line: 17p deleted patients > 2nd line: relapsed refractory patients > Toxicity - T-cell immunosuppression, CMV reactivation, fevers Rituximab: anti-CD20 > part of FCR standard 1st line

170
Q

What oral chemotherapy drug is used in CLL?

A

Chlorambucil

171
Q

What is FCR combination chemotherapy?

A

Fludarabine, cyclophosphamide and rituximab. Used to treat CLL

172
Q

What are the causes of polycythaemia in the foetus or neonate?

A
  • Twin-to-twin transfusion - Intrauterine hypoxia - Placental insufficiency
173
Q

What are some unique causes of anaemia in the foetus or neonate?

A
  • Twin-to-twin transfusion - Fetal-to-maternal transfusion - Parvovirus infection (virus not cleared by immature immune system) - Haemorrhage from the cord or placenta
174
Q

When does the first mutation that leads to acute lymphobastic leukaemia usually occur?

A

in utero. Pre-leukaemic cells carrying this mutation can even spread from one twin to another

175
Q

What type of leukaemia solely affects children with Down’s syndrome?

A

Transient myeloproliferative disease aka transient abnormal myelopoiesis (TAM) Affects 3–10% of infants, not typically serious, often resolves without treatment. 20–30% risk of developing acute lymphoblastic leukemia

176
Q

Why is sickle cell anaemia not clinically apparent at birth?

A

Clinical features manifest as gamma chain production and haemoglobin F synthesis decrease and betaS and haemoglobin S production increase.

177
Q

Why/how does sickle cell anaemia in the infant and child differ from the same disease in the adult?

A

> The distribution of red bone marrow (susceptible to infarction) differs - the hand/foot syndrome > The infant still has a functioning spleen - splenic sequestration can occur > The infant has an immature immune system and has not developed immunity to pneumococcus or parvovirus > The infant and child is growing rapidly and has a greater need for folic acid

178
Q

What is splenic sequestration?

A

> Acute pooling of a large percentage of circulating red cells in the spleen, causes the spleen to enlarge and the Hb to fall acutely and death can occur. > Doesn’t happen in older children and adults because recurrent infarction has left the spleen small and fibrotic

179
Q

Why is infection with parvovirus B19 more serious in children with sickle cell disease than in a normal child?

A

Parvovirus infection nearly completely prevents red blood cell production for 2-3 days. In normal individuals, this is of little consequence, but the shortened red cell life of sickle-cell patients results in an abrupt, life-threatening anaemia that may require transfusion.

180
Q

Why does folic acid matter more in a child with sickle cell disease than in a normal child or an adult?

A
  • Hyperplastic erythropoiesis requires folic acid - Growth spurts require folic acid - Red cell life span is shorter so anaemia can rapidly worsen
181
Q

How do we manage sickle cell anaemia and other forms of sickle cell disease in the infant and child?

A

Accurate diagnosis Educate parents Vaccinate Prescribe folic acid and penicillin

182
Q

Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count—likely diagnosis?

A

Parvovirus B19 infection

183
Q

What is beta thalassaemia?

A

A condition resulting from reduced synthesis of beta globin chain and therefore haemoglobin A. It often becomes apparent in the first 3-6 months of life. Beta thalassaemia homozygosity causes a severe anaemia that, in the absence of blood transfusion, is fatal in the first few years if life.

184
Q

What are the clinical effects of poorly treated thalassaemia major?

A

Anaemia > heart failure, growth retardation Erythropoietic drive > bone expansion, hepatomegaly, splenomegaly Iron overload > heart failure, gonadal failure

185
Q

How do we manage an infant/child with beta thalassaemia major?

A
  • Accurate diagnosis and family counselling - Blood transfusion - Once iron overload starts to occur, chelation therapy (desferioxamine, deferiprone) - Consideration of the child as an individual and as part of a family
186
Q

What specific questions can be asked in the history of a child with suspected inherited defect of coagulation?

A
  • Was there umbilical cord bleeding or bleeding when a heel-prick was done for Guthrie spot? - Was there haematoma formation after vitamin K injection of vaccinations? - Was there bleeding after circumcision?
187
Q

A 1-year-old boy presents with joint bleeding, Hb, WBC and platelet count are normal, aPTT is prolonged, PT is normal, bleeding time normal—most likely diagnosis?

A

Haemophilia A (more common than B)

188
Q

What is the treatment for autoimmune thrombocytopenia purpura?

A
  • Observation (often remits spontaneously) - Corticosteroids - High dose intravenous immunoglobulin - Intravenous anti Rh D (if Rh-positive)
189
Q

What cell marker is specific for haematopoetic stem cells?

A

CD34

190
Q

What complications can occur after a stem cell transplant?

A
  • Graft failure - Infections - Graft-versus-host disease (GVHD): allografting only - Relapse
191
Q

What different phases of immune defects are there following an allogenic bone marrow transplant?

A

Aplastic phase (0-3 wks) GVHD phase (3 wks - 6 mths) Late phase (6 mths - yrs)

192
Q

What pathogens is a patient particularly susceptible to in the aplastic phase following a bone marrow transplant?

A

Bacteria gram +/- Candida HSV RSV Influenza

193
Q

What pathogens is a patient particularly susceptible to in the GVHD phase following a bone marrow transplant?

A

CMV VZV HHV-6 Aspergillus (10-15% deaths) Candida Adenovirus

194
Q

What pathogens is a patient particularly susceptible to in the late phase following a bone marrow transplant?

A

Pneumococci H. influenzae VZV RSV

195
Q

What are some of the treatment options for GVHD?

A

Corticosteroids Cyclosporin A FK506 Mycophenylate mofetil Monoclonal antibodies Photopheresis Total lymphoid irradiation

196
Q

What treatments are used to prevent GVHD?

A

Methotrexate Corticosteroids Cyclosporin A CsA plus MTX FK506 T-cell depletion

197
Q

What drugs are frequently used as a conditioning regimen prior to stem cell transplantation and what are the common side effects?

A
  • melphalan, busulphan and cyclophosphamide - side effects include alopecia, gastro-intestinal problems of nausea, vomiting, diarrhoea and mucositis, cardiotoxicity, pulmonary fibrosis, haemorrhagic cystitis, liver toxicity known as veno-occlusive disease and gonadal failure.
198
Q

What therapy is most commonly used as a conditioning regimen prior to allogenic-SCT and what common side effects are there?

A
  • total body irradiation (TBI) - side effects include gastro-intestinal disturbance, pulmonary damage, pancreatitis, parotitis, gonadal failure and veno-occlusive disease
199
Q

How is acute GCHD defined?

A

Occurs within 100 days of SCT and usually affects the skin, gastro-intestinal tract and liver Fatal in 10% of recipients of sibling grafts and in 20% of recipients of unrelated volunteer cells

200
Q

What are the transplant related mortality figures for stem cell transplants?

A

Risk of death due to the transplant as opposed to the disease: ~5% in auto-SCT, 20-30% in sibling allo-SCT 30-50% in unrelated allo-SCT.

201
Q

What are the normal ranges for WBC, Hb, MCV, and platelet count in adults?

A

WBC Hb MCV Platelets

202
Q

Acanthyocytes

A

Spiculated RBCs Hyposplenism, liver disease, Abetalipoproteinaemia

203
Q

Basophilic RBC stippling

A

Accelerated erythropoiesis or defective Hb synthesis -> small rRNA dots on periphery. Lead poisoning, megaloblastic anaemia, MDS, liver disease, Hbopathy

204
Q

Burr cells

A

aka echinocyte (irregularly shaped) uraemia, GI bleed, stomach Ca

205
Q

Heinz bodies

A

Inclusions in RBCs G6PD deficiency Also chronic liver disease Associated with Bite cells as liver takes a bite out of RBC to remove Heinz body

206
Q

Howell-Jolly body

A

Basophilic nuclear remnants Hyposplenism (or post-splenectomy). Also megaloblastic anaemia, hereditary spherocytosis.

207
Q

Leucoerythyoblastic anaemia

A

nucleated RBCs and primitive WBCs in peripheral blood Due to marrow infiltration - myelofibrosis, malignancy

208
Q

Pelget Huet cells

A

Hyposegmented PMNs Congenital - lamin B receptor mutation Acquired - MDS - myelogenous leukaemia

209
Q

Right shift

A

Hypersegmented PMNs (>5) Megaloblastic anaemia, uraemia, liver disease

210
Q

Rouleaux

A

Red cells stack together due to hyperviscosity. Myeloma, paraproteinaemia, chronic inflammation.

211
Q

Schistocytes

A

Fragmented RBCs MAHA - DIC, TTP, HUS Pre-eclampsia

212
Q

Stomatocytes

A

Rod like RBCs with central pallor. ‘Smiling face’ or ‘Fish mouth’ appearance. Hereditary stomatocytosis High alcohol intake + liver disease

213
Q

Target cells

A

aka codocytes Bull’s eye appearance in central pallor. 3H’s - hepatic pathology - hyposplenism - Hbopathies - thalassemia (IDA)

214
Q

Pencil cells

A

IDA

215
Q

Causes of microcytic anaemia

A

FAST Fe-deficiency ACD Sideroblastic anaemia Thalassemia

216
Q

Causes of macrocytic anaemia

A

Megaloblastic: - B12 or folate - cytotoxic anti-folate drugs: phenytoin Non-megaloblastic: - Alcohol excess or liver disease - Reticulocytosis - eg. 2nd to haemolysis - Hypothyroidism - Pregnancy Other haem disorder: - MDS - myeloma - myeloproliferative disorders

217
Q

Plummer-Vinson syndrome triad

A

IDA + dysphagia + oesophageal webs

218
Q

Treatment for sideroblastic anaemia

A

Remove underlying cause (MDS, chemo, irradiation, alcohol excess, lead excess, anti-TB drugs, myeloproliferative) Pyridoxine (vitamin B6) - promotes RBC production, reducing ineffective erythropoiesis.

219
Q

Iron, TIBC and Ferritin in: IDA

A

Iron - Down TIBC - Up Ferritin - Down

220
Q

Iron, TIBC and Ferritin in: ACD

A

Iron - Down TIBC - Down Ferritin - Up (acute phase protein)

221
Q

Iron, TIBC and Ferritin in: Sideroblastic anaemia

A

Iron - Up TIBC - N Ferritin - Up

222
Q

Pernicious anaemia serology

A

Parietal cell autoAb - 90% IF autoAb - 50%

223
Q

Hereditary spherocytosis inheritance pattern

A

AutoD 25% recessive or de novo

224
Q

Hereditary spherocytosis mutations

A

Vertical cytoskeleton Band 3 - Protein 4.2 - Ankyrin - B spectrin

225
Q

Hereditary spherocytosis tests

A

Osmotic fragility - increased lysis in hypotonic solution DAT -ve Spherocytes on blood film

226
Q

Hereditary elliptocytosis mutations

A

Horizontal cytoskeleton a-spectrin - B-spectrin - protein 4.1 AutoD (except hereditary pyropoikilocytosis = autoR)

227
Q

G6PD inheritance

A

X linked

228
Q

Management of acute haemolysis

A

Folate Avoid precipitant Transfusion Immunisation vs BBVs ?cholecystectomy Splenectomy. - prophylaxis vs encapsulated bacteria.

229
Q

Precipitants of oxidative stress if G6PDD

A

Drugs - antimalarials (primaquine), antibiotics (sulphonamides) Favism (aflatoxin) Acute stressors Moth balls Acute infection

230
Q

Pyruvate kinase inheritance

A

AutoR

231
Q

Does splenic sequestration occur more in adults or children with sickle cell disease

A

Children. By adulthood it becomes atrophic.

232
Q

Diagnosis of Sickle cell disease

A

Blood film - sickle cells, target cells, boat cells, Howell-Jolly bodies Sickle solubility test Hb electrophoresis Guthrie test at birth

233
Q

Types of B thalassemia

A

Absent (B0) or Reduced (B-) B chains, excess a chains B-thalassemia minor - heterozygous B-/B; B0/B B-thalassemia intermedia - B-/B-; B0/B B-thalassemia major - homozygous B0/B0 (infant presentation)

234
Q

Type of mutation in B thalassemia

A

point mutation

235
Q

Type of mutation in a thalassemia

A

deletion

236
Q

Types of A thalassemia

A

Reduced a chain (4 genes), excess B chains a-thalassemia trait - 1/2 deleted: asymptomatic HbH disease - 3 deleted: moderate anaemia + splenomegaly Hydrops fetalis - 4 deleted: lethal

237
Q

Signs of B thalassemia

A

Anaemia - severity increases with number of mutations Skull Xray - skull bossing, maxillary hypertrophy, hairs on end skull Hepatosplenomegaly

238
Q

Donath-Landsteiner antibodies

A

Paroxysmal cold haemoglobinuria Rare AIHA. Usually affects children in acute setting after an infection. Sudden haemoglobinuria and jaundice after exposure to cold temperatures. Donath-Landsteiner Abs = IgG autoAb vs RBC surface Ags. Increasing intravascular haemolysis at low temperatures.

239
Q

Type of Ig in Warm AIHA

A

IgG WarminG

240
Q

Type of Ig in Cold AIHA

A

IgM I’M cold

241
Q

Causes of warm AIHA

A

Idiopathic - mainly Lymphoma CLL SLE methyldopa

242
Q

Causes of cold agglutinin disease

A

Primary idiopathic Lymphoma Infections - EBV, mycoplasma

243
Q

Ham’s test

A

Paroxysmal nocturnal haemoglobinuria A pig a night with red urine. Test - in vitro acid-induced lysis

244
Q

TTP pentad of symptoms

A

1) MAHA 2) Fever 3) Renal impairment 4) Neuro abnormalities 5) Thrombocytopenia

245
Q

Vascular defects: causes of

A

Congenital - Osler-Weber-Rendu syndrome (HHT) - CTD: Ehlers-Danlos, pseudoxanthoma elasticum Acquired - senile purpura - scurvy - infection - steroids

246
Q

Haemophilia A inheritance

A

X linked recessive fVIII deficiency. (intrinsic pathway - APTT prolonged)

247
Q

Haemophilia A management

A

avoid NSAIDs and IM injections Desmopressin - increases vWF release which is fVIII carrier fVIII replacement

248
Q

Treatment of ITP

A

>50,000 platelets - none 20-50,000 platelets + bleeding - steroids + IVIg <20,000 + bleeding - steroids + IVIg + admission

249
Q

Vitamin K deficiency causes

A

Warfarin Malabsorption/malnutrition Abx therapy - alters gut flora that produces vitamin K Biliary obstruction

250
Q

Antidote to heparine

A

Protamine sulphate

251
Q

Heparin-induced thrombocytopenia

A

Ab vs. heparin bound to platelets. Assoc. w/ older heparins. Treat w/ fondaparinux.

252
Q

Treatment of INR 5-8, no bleed.

A

Withold few doses, reduce maintenance. Restart when INR <5

253
Q

Treatment of INR 5-8, minor bleed.

A

Stop warfarin. Slow vitamin K po. Restart when INR<5

254
Q

Treatment on INR >8

A

Stop warfarin Vitamin K po/IV If major bleed - PCC, FFP

255
Q

% Blasts in acute leukaemia

A

Blasts >20%

256
Q

Gum hypertrophy differential

A

Acute leukaemia Drugs - cyclosporin, phenytoin, amlodipine

257
Q

Auer rods

A

AML

258
Q

ALL chemo regimen

A

Remission induction - High dose agents often given steroids Consolidation - High dose multi drug chemo CNS treatment - intrathecal chemo Maintenance - 2y in girls, 3y in boys (increased risks of testicular recurrence)

259
Q

PML mutation

A

t(15;17): PML-RARA (retinoic acid receptor)

260
Q

PML (M3 AML) treatment

A

All-trans retinoid acid (or arsenic) - neurotoxicity risk

261
Q

3 Phases of CML

A

Chronic Phase - 10% blasts - nearly 80% progress to this phase - manifestations such as splenomegaly Blast Phase - >20% blasts - resembles acute leukaemia

262
Q

CML treatment

A

Oral hydroxyurea/interferon - suppresses WCC Imatinib TKi - >95% 5 year survival Dasatinib/nilotinib for resistance (BMT, allogeneic SCT)

263
Q

Evan’s syndrome

A

AIHA + ITP assoc. w/ CLL

264
Q

Richter’s transformation

A

Progression of CLL to lymphoma (DLBC) Occurs in 3%

265
Q

Smear cells

A

CLL

266
Q

Reed-Sternberg cell

A

Hodgkin’s lymphoma Owl eyed cells with that is bi/multinucleate.

267
Q

Ann Arbor staging for lymphomas

A

Stage 1 - one LN region (can include spleen) Stage 2 - 2 or more LN regions, same side of diaphragm Stage 3 - 2 or more LN regions, opposite sides of diaphragm Stage 4 - extranodal sites (liver, BM) A: No constitutional symptoms B: Constitutional symptoms

268
Q

Hodgkin’s lymphoma Chemo combination

A

ABVD Adriamycin Bleomycin Vinblastine Dacarbazine

269
Q

Pel-Ebstein fever

A

Hodgkin’s lymphoma cyclical 1-2 week fever. Rarely seen.

270
Q

Pain in lymph nodes after drinking alcohol.

A

Hodgkin’s lymphoma

271
Q

Alemtuzumab

A

anti-CD52 (aka CamPath) Use in CLL and T cell lymphomas Also approved for use in MS.

272
Q

3 types of Burkitt’s lymphoma

A

1) Endemic - EBV-associated - Equatorial Africa. P. falciparum wears down immune system vs EBV. - Jaw involvement 2) Sporadic - EBV-associated - Out of Africa 3) Immunodeficiency - Non-EBV associated - HIV/post-transplant pts.

273
Q

Starry sky appearance on histology

A

Burkitt’s lyphoma

274
Q

Translocation in Burkitt’s

A

t(8; 14) - c-myc overexpression

275
Q

Translocation in Mantle cell lymphoma

A

t(11; 14) deregulation - cyclin D1 deregulation. Aggressive lymphoma

276
Q

Translocation in Follicular lyphoma

A

t(14;18)

277
Q

Chronic Ag stimulants leading to MALT

A

H.pylori -> gastric MALT Sjogren’s -> parotid lymphoma

278
Q

Ig in Multiple Myeloma

A

IgG

279
Q

5 solid tumours that metastasise to bone

A

Lytic 1) breast 2) thyroid 3) renal 4) lungs Sclerotic 5) Prostate

280
Q

Clinical, Plasma cell and Monoprotein for Multiple myeloma

A

CRAB >10% plasma cells >30g/L monoprotein

281
Q

Clinical, Plasma cell and Monoprotein for MGUS

A

no CRAB <30g/L monoclonal paraprotein

282
Q

Clinical, Plasma cell and Monoprotein for Smouldering myeloma

A

no CRAB >10% plasma cells >30g/L monoprotein

283
Q

Ig in Waldenstrom’s

A

IgM

284
Q

Lymphoplasmacytoid cell

A

Waldenstrom’s Macroglobinaemia

285
Q

Apple green birefringence on congo red stain

A

Amyloidosis

286
Q

Fanconi anaemia

A

AutoR Paediatric: 5-10y Pancytopenia. Skeletal abnormalities (radii + thumbs). Renal malformation. Microopthalmia. Short. Skin pigmentation.

287
Q

Dyskeratosis congenita

A

X linked Telomere shortening TRIAD: skin pigmentation + nail dystrophy + oral leukoplakia. Also BM failure

288
Q

Schwachmann-Diamond syndrome

A

AutoR PRoPoSe - Pancreastic insufficiency - Recurrent infection - Pancytopenia - Skeletal abnormalities Neutrophilia

289
Q

Diamond-Blackfan syndrome

A

Pure RED cell aplasia. Neonatal/infant presentation.

290
Q

AutoR Paediatric: 5-10y Pancytopenia. Skeletal abnormalities (radii + thumbs). Renal malformation. Microopthalmia. Short. Skin pigmentation.

A

Fanconi anaemia

291
Q

X linked Telomere shortening TRIAD: skin pigmentation + nail dystrophy + oral leukoplakia. Also BM failure

A

Dyskeratosis congenita

292
Q

AutoR PRoPoSe - Pancreastic insufficiency - Recurrent infection - Pancytopenia - Skeletal abnormalities Neutrophilia

A

Schwachmann-Diamond syndrome

293
Q

Mutation in polycythemia rubra vera

A

JAK2 (V617F) - point mutation. Activation of STAT pathway leading to cellular proliferation.

294
Q

Aquagenic pruritus + peptic ulcers + gout + erthromelagia

A

Polycythemia rubra vera Aquagenic pruritus - contact with hot water -> histamine release Histamine -> peptic ulcer Erythromelagia (red, painful extremities) and gout due to hyperviscosity.

295
Q

Treatment for PRV

A

Venesection - keep haematocrit <45% Hydroxycarbamide - cytoreductive therapy for maintenance. Aspirin - reduce thrombosis risk

296
Q

Tear-drop poikilocytes

A

Myelofibrosis aka dacrocytes

297
Q

Dry tap BM trephine

A

myelofibrosis. Fibrotic replacement of BM. High reticulin.

298
Q

Anagrelide treatment

A

Used in essential thrombocythemia. Reduces formation of plts from megakarocytes. Used in conjunction with aspirin (anti-thrombotic) and hydroxycarbamide (cytoreductive).

299
Q

Ig in haemolytic disease of the newborn

A

IgG. Only it can cross the placenta.

K1s Path (16 decks)

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