Haematology Flashcards

Question

How do you manage ET?

Answer 1

1. Treat with aspirin and hydroxyurea until PLT <600 | 2. Consider interferon alpha if pregnant

Answer 2

Stage 1 - B2MG <3.5, albumin >35 Stage 2 - B2MG between 3.5 and 5.5, albumin <35 Stage 3 - B2MG >5.5

Answer 3

``` del13 del17p t(4;14) ```

Answer 4

APTT and dabigatran shows some linear relationship. Thrombin clotting time is exquisitely sensitive to presence of any dabigatran therefore high level indicates that dabigatran is present.

Answer 5

1. Dabigatran would be minimally present/not present 2. Likely presence of low dabigatran activity 3. Significant drug activity present. Do a modified thrombin time.

Answer 6

Via modified anti-Xa level which needs to be drug specific. APTT/PT are completely unreliable.

Answer 7

decoy factor Xa receptor which has no protease function which binds to rivaroxaban/apixaban with higher affinity than natural factor Xa thereby reversing its effect.

Answer 8

Depends on level of factors. Severe <1% Moderate 1-5% Mild 5-40%

Answer 9

Factor prophylaxis was effective in reducing joint damage, however was associated with greater factor 8 units transfused and significant cost.

Answer 10

Mutations of genes encoding ankyrin, spectrin, or band 3 red cell proteins.

Answer 11

Look at the megakaryocytes which are the most reliable lineage to use. Small mononuclear or aberrant megakaryocytes are typical of MDS, whereas megakaryocytes are markedly reduced or absent in severe AA.

Answer 12

around 50%. Mutation of PIGA responsible for PNH occurs in setting of acquired aplastic anaemia.

Answer 13

Serum viscosity of around 4.08 cP which corresponds to serum IgM level of 30g/L

Answer 14

splenic marginal zone lymphoma

Answer 15

Genetic, chronic systemic disorder due to uncontrolled complement activation. Associated with mutation in genes encoding both complement regulators (factor H, I, membrane cofactor protein and thrombomodulin) and activators (factors B and C3)

Answer 16

1. Mucocutaneous candidiasis 2. Hypoparathyroidism 3. Addisons disease Also at risk of developing other autoimmune diseases including type 1 DM, hypothyroidism, pernicious anaemia, alopecia, vitiligo, hepatitis, ovarian atrophy and keratitis.

Answer 17

type 1: partial reduction in vWF (80% of patients) type 2: abnormal form of vWF type 3: total lack of vWF (autosomal recessive)

Answer 18

VDRL and RPR reagent contains cardiolipin.

Answer 19

About 30-40% | 5% have lupus like syndromes

Answer 20

Usually of IgM type. 1. Antiepileptics - phenytoin, ethosuximide 2. Amoxicillin 3. Hydralazine 4. Chlorothiazide

Answer 21

Study looking at aspirin prophylaxis in individuals with aPL positivity: ●Asymptomatic individuals who are persistently positive for aPL have a low annual incidence of acute thrombosis. ●These individuals do not benefit from low-dose aspirin. ●Thrombotic events in this population are unlikely in the absence of additional risk factors for thrombosis

Answer 22

1. Aspirin and hydroxychloroquine will reduce the thrombotic risk 2. Address modifiable risk factors such as smoking, hyperlipidaemia, hypertension 3. If clot occurs, manage with clexane then warfarin. Currently no evidence exists for NOACs.

Answer 23

``` Uroporphyrinogen decarboxylase (UROD) Results in acccumulation of uroporphyrinogen and hepta, hexa and penta-carboxyl prophyrinogen in the liver, which then accumulates in the skin and are photosensitizing, and cause LFT derangements. ```

Answer 24

ALA synthase Responsible for pathway between formation from glycine+succinyl-COA to delta-aminolevulinic acid

Answer 25

1. High leucocyte alkaline phosphatase score 2. Toxic granulation in the WBCs (Dohle bodies) 3. Left shift of neutrophils - ie, 3 or less segments of the nucleus

Answer 26

1. Clearance of microorganisms and particulate antigens from the blood stream 2. Synthesis of immunoglobulin G (IgG), properdin (an essential component of the alternate pathway of complement activation), and tuftsin (an immunostimulatory tetrapeptide) 3. Removal of abnormal red blood cells (RBCs) 4. Extramedullary hematopoiesis in certain diseases

Answer 27

1. Immune work hypertrophy (eg sepsis) 2. RBC destruction work hypertrophy 3. Congestive (Splenic vein thrombosis, CLD) 4. Myeloproliferative - CML 5. Neoplastic - CLL, lymphoma 6. Infiltrative - sarcoidosis

Answer 28

Reduced bone marrow iron stores on BM aspirate - Perl stain for haemosiderin.

Answer 29

GPI is a glycolipid which acts as an anchor for adherence of CD55/59 on the RBC surface, making them more susceptible to complement-mediated destruction.

Answer 30

BSS: Autosomal recessive defect in glycoprotein Ib-Ix, the vWF receptor. GT: Low level/defective GP IIb/IIIa, a fibrinogen receptor

Answer 31

1. Progressive marrow failure 2. B symptoms 3. Doubling time <6 months 4. Bulky disease as defined by LN >10cm, massive splenomegaly (>6cm below costal margin), progressive symptomatic lymphadenopathy 5. Uncontrollable autoimmune phenomena (ITP or AIHA)

Answer 32

Mutation of HFE gene in HLA class I region on chromosome 6. Missense mutation: 1. C282Y mutation - substitution of tyrosine for cysteine at amino acid position 282 2. H63D - aspartic acid substituted for histidine in position 63 C282Y homozygosity or compound heterozygosity is found in most patients with HH.

Answer 33

1 All homozygotes with clinical evidence of liver disease 2. All homozygotes with serum ferritin >1000 3. All homozygotes older than age 40 with other risk factors for liver disease 4. Compound C282Y heterozygotes with elevated transferrin saturation, particularly those who have had abnormal liver enzymes or clinical evidence of liver disease.

Answer 34

Transferrin saturation >45% in the absence of other causes of iron overload. A value greater than 60% in men and 50% in women is highly specific. However, approximately 30% of women younger than 30 years who have hemochromatosis do not have elevated transferrin saturation. At present, only homozygosity for C282Y and compound heterozygosity for C282Y/H63D should be considered indicative of hereditary hemochromatosis. C282Y heterozygosity may contribute to iron overload due to other conditions, but it should not be considered the sole cause of iron overload and it should not be considered diagnostic of hereditary hemochromatosis.

Answer 35

1. In the induction phase, weekly phlebotomy with blood removal of 7 mL/kg per phlebotomy (not to exceed 550 mL per phlebotomy). 2. Monthly ferritin evaluation until down to normal range, then bimonthly until ferritin <50 3. In the maintenance phase, the phlebotomy should be performed every 2-4 months. The interval between procedures is determined by the level of ferritin, which should be lower than 50 mcg/mL 4. If concurrent anaemia precludes phlebotomy - use iron chelation agent 5. Avoid oral iron loading with food, medications etc, avoid alcohol

Answer 36

1. Idiopathic - 50% 2. Autoimmune 15% 3. Malignancy 12% 4. Peripartum factor 8 inhibitor 8%

Answer 37

Replace the factor, then remove the antibody. Replacement depends on titre of the antibody: 1. High titre antibody >5 bethesda units - Recombinant factor 7a - Activated prothrombin complex concentrate - Porcine factor 8 concentrate 2. Low titre antibody - Human or porcine factor 8 concentrate - Desmopressin Remove the antibody with Rituximab, cyclophosphamide, cyclosporin, IVIG, or plasmapheresis.

Answer 38

1. Anaemia 2. Bone marrow fibrosis 3. Extramedullary haematopoiesis 4. Hepatosplenomegay 5. Leucoerythroblastosis with tear drop cells in blood film JAK 2 positive in 50-60% Majority of JAK 2 negative patients have CAL-R mutation

Answer 39

1. Portal hypertension - increased portal flow resulting from marked splenomegaly and to intrahepatic obstruction resulting from thrombotic obliteration of small portal veins. May need splenectomy 2. Splenic infarction - analgesia, splenectomy, splenic radiation 3. Increased susceptibility to infection 4. Extramedullary haematopoiesis - can involve any sites, may result in bleeding, spinal cord compression, seizures, hemoptysis, and/or effusions. Treated with low dose radiation 5. Osteosclerosis causing pain

Answer 40

The median length of survival for patients with primary myelofibrosis is 3.5-5.5 years. The 5-year survival rate is about half of that expected for age- and sex-matched controls. Fewer than 20% of patients are expected to be alive at 10 years. [13] The common causes of death in patients with primary myelofibrosis are infections, hemorrhage, cardiac failure, postsplenectomy mortality, and leukemic transformation. Leukemic transformation occurs in approximately 20% of patients with primary myelofibrosis within the first 10 years. CAL-R positivity is a favourable prognostic factor. Use DIPSS scoring for prognostication.

Answer 41

JAK1/2 inhibitor Used in primary myelofibrosis. Effective in reduction of spleen volume, symptoms, quality of life

Answer 42

1. Hydroxyurea 2. IFN alpha in young patients - 50% responds with improvement in splenomegaly and anaemia 3. Androgens (such as danazol) - 30% respond 4. Thalidomide and prednisone - may improve cytopenias, however also increases WBCs or platelets significantly in the first 4-8 weeks, and may require further cytoreductive therapy 5. Splenectomy may be considered for patients with overt portal hypertension, progressive anemia requiring transfusions, or symptomatic splenomegaly refractory to hydroxyurea. However splenectomy is associated with high perioperative risk, and higher risk of transformation to AML.

Answer 43

Hydroxyurea is an inhibitor of deoxynucleotide synthesis. It is less leukemogenic than alkylating agents (busulfan) are. Hydroxyurea's myelosuppressive effects last a few days to a week and are easier to control than those associated with alkylating agents. It is lethal to cells in the S phase and is cell-cycle specific

Answer 44

HbC is astructural variant of normal hemoglobin A (Hb A) caused by an amino acid substitution of lysine for glutamic acid at position six of the beta hemoglobin chain. This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy. In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops. In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia Hemoglobin C is mainly of clinical significance when inherited in combination with Hb S (Hb SC disease), or when co-inherited with β-thalassemia (hemoglobin C–β thalassemia). In HbSC - less vasoocclusive crisis, but more significant retinopathy, ischemic necrosis of bone, and priapism compared to pure HbSS

Answer 45

The oxygen carrying capability of the red blood cells (RBCs) relies on hemoglobin, a tetramer protein that comprises 4 globin chains bound to the heme molecule. There are 4 major types of globins: alpha (α), beta (β), gamma (γ), and delta (δ). The dominant hemoglobin in adults (hemoglobin A) is composed of 2 alpha and 2 beta chains. Two minor forms of hemoglobin constitute a small percentage of normal blood: hemoglobin F (fetal), composed of 2 alpha chains and 2 gamma chains, and hemoglobin A2, composed of 2 alpha chains and 2 delta chains.

Answer 46

1. Silent carrier - (-α/αα) or alpha thalassemia-2 trait. No clinical abnormalities and may be hematologically normal or have slight reductions in RBC mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). 2. Alpha thalassemia trait Inheritance of 2 normal alpha-globin genes through either heterozygosity for alpha(0) thalassemia (αα/--) or homozygosis for alpha(+) thalassemia (-α/-α). Clinically normal but frequently have minimal anaemia and reduced MCV and MCH. 3. Haemoglobin H disease (-α/--) or aka alpha thalassemia intermedia. Abundant formation of HbH which is characterized by a high ratio of beta globin to alpha globin and a 2-fold to 5-fold excess in beta-globin production. The excess beta chains aggregate into tetramers, which account for 5-30% of the hemoglobin level in patients with HbH disease. HbH has a high affinity for oxygen and has no Bohr effect or heme-heme interaction; therefore, it is an ineffective supplier of oxygen to the tissues under physiologic conditions. RBCs that contain HbH are sensitive to oxidative stress; thus, they may be more susceptible to haemolysis when oxidants such as sulphonamides are administered.

Answer 47

Heinz bodies, which represent inclusions within RBCs consisting of denatured hemoglobin (Hb), may also be seen in the peripheral blood. [7] Elevation of the Hb A2 level, demonstrated by electrophoresis or column chromatography, confirms the diagnosis of beta thalassemia trait. The Hb A2 level in these patients usually is approximately 4-6%. In rare cases of concurrent severe iron deficiency, an increased Hb A2 level may not be observed, although it becomes evident with iron repletion. The increased Hb A2 level also is not observed in patients with the rare delta-beta thalassemia trait. An elevated Hb F level is not specific to patients with the beta thalassemia trait. In contrast, alpha thalassemia has normal HbA2 level. Establishing the diagnosis of the alpha thalassemia trait requires measuring either the alpha-beta chain synthesis ratio or performing genetic tests of the alpha-globin cluster (using Southern blot or polymerase chain reaction [PCR] assay tests

Answer 48

Due to 3 alpha gene deletion | Leads to formation of 2 types of unstable tetramers consisting of 4x gamma chains (Hb Barts) and 4x beta chains (HbH)

Answer 49

●High-risk disease – History of thrombosis at any age and/or age >60 with a JAK2 V617F mutation ●Intermediate-risk disease – Age >60, no JAK2 mutation detected, and no history of thrombosis ●Low-risk disease – Age ≤60 with JAK2 mutation and no history of thrombosis ●Very low-risk disease – Age ≤60, no JAK2 mutation detected, and no history of thrombosis High risk - anticoagulation +/- aspirin and hydroxyurea Intermediate risk - could consider hydroxyurea Low/very low risk - aspirin if symptoms or cardiovascular risk factors are present, otherwise observe only

Answer 50

1. Normocytic, normochromic anemia; rarely, macrocytic 2. A very low (or zero) reticulocyte percentage, and an absolute reticulocyte count <10,000/microL 3. Normal white blood cell and platelet counts 4. A normocellular bone marrow that shows normal myelopoiesis, lymphopoiesis, and megakaryocytopoiesis, but few if any erythroid precursors.

Answer 51

1. Idiopathic (presumed immune mediated) 2. Thymoma 3. Haem malignancies - LGL, myeloma, MDS etc 4. Parvovirus infection 5. ABO incompatible haematopoietic transplantation 6. Drugs - phenytoin, cotrimoxazole, EPO (Anti-EPO antibodies)

Answer 52

1. Supportive treatment initially 2. If no remission despite supportive treatment, prednisone 3. If prednisone does not work, then either cyclosporine or cyclophosphamide. Cyclosporine has better response rates than cyclophosphamide.

Answer 53

Normal body iron content - 3-4g 2g in RBC haemoglobin Proteins (myoglobin, cytochrome, catalase) - 400mg Plasma iron bound to transferrin - 3-7mg Rest are in storage iron - haemosiderin and ferritin in liver, spleen and bone marrow

Answer 54

Absorbed iron can be Non-Haem iron (90%) or haem iron (10%). Absorbed in the duodenum. Non haem iron are absorbed in Ferrous state Fe2+ into duodenal cells via DMT1. Exported out from duodenal enterocytes into plasma via ferroportin. Haem iron are complexed with protoporphyrin and are more bioavailable. Absorption is not well understood. Iron in plasma is carried by transferrin. Transferrin receptors mediates uptake into cells.

Answer 55

Transferrin saturation reduced Transferrin increased Increased TIBC Reduced ferritin Soluble transferrin receptors increased - directly proportional to erythropoietic state, inversely proportional to iron stores.

Answer 56

B12: Fish, meat, poultry, eggs, milk products Folate: diet is the only source. In fruit and vegetables, beef. Absorbed in small bowel.

Answer 57

Intrinsic factor antibodies - very specific, but only 50% sensitive Parietal cell antibodies - sensitive but non specific (positive in 15% of normal females) Therefore ideally should test for both!

Answer 58

Red cell folate - 95% of folate is in RBCs. Best assessment of long term stores and is less variable. Serum folate is indicative of recent intake and is susceptible to variation.

Answer 59

1. Fragmentation (eg: causes of MAHA, DIC, mechanical haemolytic anaemia, preeclampsia, malignant hypertension) 2. PNH 3. Paroxysmal cold haemoglobinuria

Answer 60

1. Red cell membrane defect 2. RBC enzyme defect (eg: G6PD deficiency) 3. Immune mediated 4. Metabolic defect 5. Bacteria/parasitic infections such as malaria

Answer 61

1. HUS/TTP 2. aHUS - inherited dysregulation of complement system due to mutation in complement factor H gene 3. Renal allograft reejction 4. Pre-eclampsia/HELLP 5. Malignant hypertension

Answer 62

1. haemolysis with RBC fragmentation 2. Renal failure 3. Neurological impairment 4. Thrombocytopenia 5. Fever

Answer 63

1. Plasma exchange - urgent, to get rid of large vWF and replace normal ADAMTS13 3. Avoid platelet transfusion Further management depends on specific aetiology 1. If aHUS - eculizumab 2. If hereditary TTP - ADAMTS13 replacement with FFP infusions 3. Immunosuppression with rituximab and prednisone if it is an autoimmune cause of ADAMTS13 deficiency

Answer 64

Somatic mutation of pig-A gene (phosphatidylinositol glycan A) which is essential for the formation of GPI anchor. Results in loss of several surface proteins which usually protects cells from complement mediated damage - CD55/59. Manifests paroxysmal intravascular haemolysis Increased risk of thrombosis eg: in large veins such as portal veins Diagnose with flow cytometry testing for CD55/59 on red cells and neutrophils. Treatment - transfusion, stem cell transplant, thrombosis management, eculizumab (recues transfusion requirement and cessation of haemoglobinuria)

Answer 65

Rare form of AIHA with acute intravascular haemolysis after exposure to cold. Due to presence of biphasic IgG anti-P antibody (Donath-Landsteiner antibody) which binds to RBC at low temperatures and upon warming complement mediated lysis occurs. Management - cold avoidance, folate supplement, prednisone, IVIG. Unlike other AIHAs, splenectomy is NOT USEFUL.

Answer 66

1. Prednisone 1mg/kg then taper 2. Splenectomy and vaccination (after steroids, best second line therapy) 3. Rituximab Supportive treatment such as IVIG and folate supplement are also important.

Answer 67

Almost always secondary cause - associated with lymphoproliferative disease, mycoplasma, EBV, autoimmune disease. IgM mediated causing both intravascular and extravascular haemolysis. Management: cold avoidance, chlorambucil especially if underlying LPD, rituximab. Unlike warm AIHA, does not respond to splenectomy or steroids.

Answer 68

Often due to mutation of ankyrin, spectrin Autosomal dominant. Family history in 75% Typical blood film picture of polychromasia, prominent spherocytes and family history is enough to make the diagnosis. Flow cytometry will show reduced eosin-5-maleimide binding (EMA) Management is with folate supplementation, splenectomy.

Answer 69

Autosomal recessive, rare. RBC glycolytic pathway is affected with reduced ATP formation leading to RBC rigidity. Results in chronic haemolysis.

Answer 70

X linked, common. G6PD is involved in hexose-monophosphate shunt which allows regeneration of NADPH which is important for generating reduced glutathione. Reduced glutathione absorbs oxidative stress. Increased susceptibility to oxidative stress and episodes of acute haemolysis. Hemizygous males are affected. Homozygous females are affected. Heterozygous females have variable manifestations depending on extent of X inactivation.

Answer 71

Test for enzymes when patient is STABLE. | If tested during acute haemolysis, can be falsely negative as reticulocytes have higher G6PD levels.

Answer 72

ITP is a diagnosis of exclusion - need to look for disease associations: 1. Lymphoproliferative diseases eg CLL 2. Autoimmune disease RA/SLE 3. H pylori 4. Hep C

Answer 73

Aim of the management is to maintain platelet count high enough to prevent significant bleeding. 1. Can observe if >30 2. Prednisone 1-2mg/kg (high response rate but also high relapse rate) 3. IVIG - more rapid response 4. Splenectomy with vaccination is the most effective therapy. Other therapies include immunosuppressive meds such as azathioprine, rituximab, danazol

Answer 74

IgG antibody that recognizes heparin-PF4 complex and causes platelet activation and consumption via Fc receptor. Typically develops 5-14 days after heparin commencement Heparin falls by >50% but rare to have severe thrombocytopenia <15 High risk of thrombosis. PF4 immunoassay has high sensitivity but low specificity (therefore useful if negative)

Answer 75

HbA - a2b2, main haemoglobin HbA2 - a2d2, minor haemoglobin 2-3% Hb F - a2y2, primarily from neonates, minor haemoglobin in adults.

Answer 76

a0 thalassaemia - deletion or inactivation of both alleles on a single chromosome. If both chromomes are a0, then it leads to hydrops fetalis and intrauterine death a+ thalassaemia - one allele inactivation on the single chromosome. 3 subtypes exist: 1. Silent carrier a-aa 2. Alpha thalassaemic trait aa-- or a-a- 3. HbH disease -a--

Answer 77

No. Requires molecular studies to diagnose. If you have alpha thalassaemic trait with --aa, they may occasionally have HbH cells. However with a-a- phenotype, HbH cells are rare.

Answer 78

1 gene deletion resulting in reduced beta globin synthesis. As a result, reduced HbA (a2b2) formation, with compensated increase in HbA2 (a2d2) as there are excess alpha chains. Mild anaemia only on FBC. Clinically asymptomatic. High performance liquid chromatography will show increased HbA2 and HbF

Answer 79

Iron deficiency. Reduces Hb A2 level therefore must always assess iron status.

Answer 80

1. Transfusion support - aim Hb 90-100 to suppress extramedullary haematopoiesis 2. Manage endocrine failures - sex hormones, thyroid disease, GH 3. Stem cell transplant 4. Iron chelation therapy - generally to aim ferritin <1000. Ferritin >2500 associated with high cardiac risk.

Answer 81

Abnormal hemoglobin in which substitution of a glutamic acid residue with a lysine residue at the 6th position of the β-globin chain Heterozygosity for HbC is clinically silent - homozygosity results in mild haemolytic anaemia as this mutated form has reduced RBC plasticity.

Answer 82

Glutamine to valine substitution at codon 6 Autosomal recessive Management is with hydroxyurea which causes foetal haemoglobin induction with decrease in HbS level in blood Transfuse as required Monitor HbS level

Answer 83

Once HH due to C282Y homozygosity or compound heterozygosity C282Y/H63D is diagnosed, initiation of treatment depends on ferritin level: 1. Ferritn 300-1000 with normal LFTs - start phlebotomy 2. Ferritin >1000 and/or LFTs abnormal – liver biopsy to confirm iron overload, then start phlebotomy 3. Ferritin <300 and normal LFTs – observe, retest in 1 year

Answer 84

LAC - strong risk factor for both venous and arterial thrombosis (RR 3-10 for venous, RR 10 for arterial) ACLA - associated with arterial thrombosis (RR 1.5-10) but NOT WITH VENOUS THROMBOSIS. Anti-B2 glycoprotein - associated with venous thrombosis with RR 2.4.

Answer 85

Prevalence of JAK 2 was 49% in patients with idiopathic SVT

Answer 86

Factor 10 and 5 requires phospholipids to act on in order to cause thrombin formation. Russel viper venom stimulates ++ factor X to become Xa directly. For this to occur, phospholipids need to be present. APLA binds to phospholipids and delay these reactions from happening - therefore DRRV test is SENSITIVE to presence of APLA. False positives can occur with anti-Xa drugs.

Answer 87

Low phospholipid reagents which are sensitive to presence of LA.

Answer 88

1. Stop transfusion 2. Vigorous IVF to induce diuresis and to avoid renal failure 3. DAT, Hb level and repeat group and hold and cross match, urine for haemosiderin testing 4. Alert blood bank immediately

Answer 89

Due to an anamnestic antibody response occurring after re-exposure to a foreign red cell antigen previously encountered by transfusion, transplantation, or pregnancy. The antibody, often of the Kidd or Rh system, is undetectable on pretransfusion testing but increases rapidly in titrefollowing the transfusion. Seen generally within 3 to 30 days after transfusion. Hemolysis is usually extravascular, gradual, and less severe than with acute reactions, but rapid hemolysis can occur. A falling hematocrit, slight fever, mild increase in serum unconjugated bilirubin, and spherocytosis on the blood smear may be noted. The diagnosis is often made by the blood bank when a new positive direct antiglobulin test and a new positive antibody screen are found when more blood is ordered.

Answer 90

CEBPA mutation - good prognosis NPM1 mutation/FLT3-ITD negative - good prognosis FLT3-ITD positive - bad prognosis

Answer 91

When compared with low dose ara-C, improves overall survival, transfusion independence, quality of life.

Answer 92

Number of blasts - RAEB1 has 5-9% blasts, while RAEB2 has 10-19% blasts. Accordingly RAEB2 has higher 5 year risk of AML (21% vs 34.5%)

Answer 93

RARS - refractory anaemia with ringed sideroblast. Has >15% ringed sideroblasts.

Answer 94

Direct coombs test - used to test for AIHA. Patient's blood is taken then RBCs are incubated with antihuman antibodies (coomb's reagent). If RBCs are coated with autoimmune antibodies, then RBCs will agglutinate. Indirect coombs test - Used to test antigens on RBC surface eg for ABO incompatibility testing. Donor RBCs are combined with recipient's serum (which will have antibodies) then coomb's reagent is added to see if agglutination occurs (which means that the recipient's antibodies have coated the donor RBCs)

Answer 95

Splenic macrophages have Fc receptors which recognize IgG1 and IgG3 only. Corticosteroids downregulate Fc receptors on macrophages and also decrease autoantibody formation. Splenectomy removes major site of RBC destruction. However given that the splenic macrophages only remove IgG coated cells, it doesn't remove antibodies targeting C3b on RBCs which are destroyed in liver.

Answer 96

Transferrin synthesized in the liver. Production increased in Fe deficiency, also induced by OCT, HRT. Production decreased in iron overload and also acute inflammation/infection (acute phase negative reactant)

Answer 97

Disrupts HFE-B2MG-TFR1 complex. HFE-B2MG complex usually interacts with transferrin receptor and decreases the affinity of the transferrin receptor for interaction with transferrin. C282Y mutation leads to increased iron transfer into stores and also increases the expression of DMT1 on intestinal cells leading to increased absorption.

Answer 98

Asthenia - fatigue, impotence Arthralgia - especially 2nd and 3rd MCPJ Aminotransferase elevation

Answer 99

Weekly venesection until ferritin <50 and transferrin saturation <20% Then maintain ferritin <100 Venesection improves asthenia, LFT derangements and pigmentation. Some improvement in arthralgia and diabetes No effect on impotence, cirrhosis and HCC. Therefore need to venesect in the EARLY stages of the disease before end organ complications occur.

Answer 100

When serum iron exceeds transferrin, iron is bound to low molecular weight compounds to form non transferrin bound iron (NTBI). NTBI is readily taken up by hepatocytes and cardiac myocytes and anterior pituitary cells and pancreatic beta cells and cause oxiant damage.

Answer 101

LCDD - light chains (mainly kappa) deposited in glomerulus causing glomerulosclerosis. Cast nephropathy - causes direct tubular cellular damage, formation of cast leading to decreased tubular urine flow. Kappa light chains are more likely to cause LCDD and PCT dysfunction, while as lambda light chains are more likely to cause AL amyloidosis.

Answer 102

1. Size of the M band 2. IgM or IgA monoclonal protein had an increased risk of progression to disease compared to IgG 3. Elevated serum free light chains

Answer 103

1. Constipation 2. Tremor 3. Painful neuropathy 4. Thrombosis 5. Oedema Thalidomide and lenalidomide as a single agent does not increase the thrombotic risk significantly, but risk increases if concurrent dexamethasone use or chemotherapy. Therefore consider aspirin, LMWH prophylaxis or warfarin if concurrent thal/dex or len/dex use depending on patient's thrombotic risk.

Answer 104

Melphalan and prednisone in combination with either thalidomide or bortezomib. Melphalan cannot be used in AuSCT eligible patients as they are stem cell toxic.

Answer 105

1. Viral: Parvovirus B19 (although more commonly causes PRCA), HBV/HCV, HIV, EBV 2. Chemical - benzene, glue vapours 3. PNH - 1/3 develop AA 4. Thymoma 5. Immune mediated - SLE, GvHD, eosinophilic fasciitis Most cases in adults are however idiopathic (80%) Pregnancy can also cause transient AA.

Answer 106

Depending on severity - if moderate (ie, BM cellularity <30% with 2/3 cell lines reduced), supportive treatment with antibiotics and treatment. If severe, needs definitive treatment with: 1. Immunosuppression - IV ATGAM (horse), prednisolone, cyclosporine maintenance therapy to maintain response 2. Allogeneic stem cell transplant Younger age ie <49 years, aim early allogeneic transplant with little transfusion as possible (due to risk of alloimmunization) Older age >50 - immunosuppression as risk of GvHD and transplant related mortality is too high.

Answer 107

Both are made by injecting human thymocytes and harvesting antibodies. Horse ATG is superior to rabbit ATG in terms of overall response rate and 5 year overall survival. Therefore use horse ATG first line over rabbit ATG.

Answer 108

Risk is relatively low down to around 0.5 x 10e9, then rises sharply. Risk is greater in context of: 1. Falling count (progressively decreasing availability) 2. Lack of precursors 3. Prolonged length of neutropenia

Answer 109

1. Carbimazole 2. PTU 3. Sulphonamides 4. Antiepileptics 5. Rituximab

Answer 110

1. Drugs 2. Viral (hep B, HIV) 3. Severe bacterial sepsis - poor prognosis 4. Nutritional - B12/folate/copper deficiency 5. Hypersplenism Blood taken from during haemodialysis can cause falsely negative neutrophil count as dialysis membrane causes complement activation and causes attachment of neutrophils onto lung endothelium. Not a true neutropenia.

Answer 111

1. Chronic idiopathic neutropenia - neutrophil equivalent of adult ITP. most are mild and never requires treatment. Diagnosis of exclusion. Seen in autoimmune diseases 2. LGL syndrome - neutropenia associated with increased large granular lymphocyte syndromes (such as NK cells). Not malignant, may regress spontaneously. 3. Felty's syndrome - triad of RA, splenomegaly and neutropenia. 1% of RA patients. Probably AI basis and seen in higher RF/ANA levels. often also have LGL syndrome concurrently.

Answer 112

Autosomal dominant mutation of neutrophil elastase (ELANE). Usually mild but can be severe. Cyclic neutropenia over 3 weeks. Regular GCSF reduces nadir and risk of infection.

Answer 113

Levels of vWF correlate with ABO blood type. Individuals with type O blood normally have the lowest levels of vWF, approximately 50-75% of the vWF levels found in persons with other blood types. vWF levels should be compared with an ABO blood group type–specific range from the laboratory where the test is performed.

Answer 114

Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin and preserves the framework of fibrin's matrix structure

Answer 115

FFP transfusion is indicated in hemorrhaging patients to replace labile and lost coagulation factors. Clinical circumstances fulfilling this criterion include: 1. Massive transfusion 2. Cardiopulmonary bypass 3. Extracorporeal pulmonary support techniques 4. Decompensated liver disease 5. DIC regardless of the cause Plasma contains all of the coagulation factors. Fresh frozen plasma infusion can be used for reversal of anticoagulant effects. Thawed plasma has lower levels of factors V and VIII and is not indicated in patients with consumption coagulopathy

Answer 116

Cryoprecipitate is prepared by thawing fresh frozen plasma at 4 degrees and collecting the precipitate. Cryoprecipitate contains high concentrations of factor VIII and fibrinogen and vWF. Cryoprecipitate is used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy.

Answer 117

Non-linear relationship. Zone of normal haemostasis is anywhere between INR of 1.0 to 2.0. Around INR of 2.0, coagulation factor level is around 30%.

Answer 118

1. Heparin 2. Dysfibrinogenaemia 3. Hypofibrinogenaemia 4. Increased fibrin degradation product - interferes with fibrin polymerisation 5. Thrombin inhibitor eg dabigatran

Answer 119

1. Platelet dysfunction - mucosal bleeding, petechiae, prolonged bleeding from skin cuts 2. Coagulopathy - deep haematomas and haemarthroses. Tends to be males. Mucosal bleeding/petechiaes are rare.

Answer 120

30% | Others are X linked recessive.

Answer 121

1. Stroke prevention for non-valvular AF 2. Thromboprophylaxis post hip and knee replacement surgery Rivaroxaban - as above plus treatment of acute DVT and prevention of DVT/PE.

Answer 122

Depends on stage. 1. Limited stage - abbreviated ABVD 4 cycles + radiotherapy 2. Stage IIB/Advanced stage - either full 6 cycles of ABVD or eBEACOPP.

Answer 123

Adriamycin Bleomycin Vinblastine Darcabazine. Side effects - hair loss, neutropenia, heart/lung toxicities from Adriamycin and bleomycin. Low risk of infertility compared to eBEACOPP.

Answer 124

1. Repeat chemotherapy followed by AuSCT 2. Brentuximab vedotin - CD30 monoclonal antibody which delivers cytotoxic MMAE, a potent antitubulin agent. CD30 is expressed in HRS cells.

Answer 125

Standard of care. PRIMA study shoed that rituximab 2 monthly maintenance therapy prolonged remission compared to observation only.

Answer 126

Dual positivity to BCL-2 and C-MYC. Portends a poor prognosis with chance of survival at 33%. Needs high intensity chemotherapy involving R-CHOEP or other high intensity protocol such as hyperCVAD, AuSCT.

Answer 127

Formed from thawing fresh frozen plasma at 4 degrees and removing the precipitate. Rich in fibrinogen, vWF, factor 8 and 13

Answer 128

Main source of B12 is from fish, poultry, egg, milk, meat. 1. Ingested B12 released from food via pepsin and acid 2. Initially bound to R protein (transcobalamin I or haptocorrin) 3. Pancreatic enzymes release cobalamin from R protein and allow binding to IF (secreted from paretal cells) 4. At terminal ileum, B12-IF complex binds to receptor (cubilin), uptake by receptor mediated endocytosis and absorbed into the portal blood system. Circulates in the blood as transcobalamin 2-B12 complex.

Answer 129

Pernicious anaemia - autoimmune destruction of gastric mucosa/parietal cells leading to atrophic gastritis and reduced IF. Associated with blood group A, vitiligo, thyroid disease, addisons disease.

Answer 130

Based on attempts of improving quality of life: 1. Local symptoms due to progressive or bulky nodal disease 2. Compromise of normal organ function due to progressive or bulky disease 3. Presence of systemic B symptoms (ie, fevers, weight loss, night sweats) 4. Presence of symptomatic extranodal disease, such as effusions 5. Cytopenias due to extensive bone marrow infiltration, autoimmune hemolytic anemia or thrombocytopenia, or hypersplenism 6. An increase in disease tempo Treatment regimen can be either bendamustine and rituximab with rituximab maintenance, R-CHOP, RCVP

Answer 131

1. RCC 2. HCC 3. Pheochromocytoma 4. Uterine fibroids

Answer 132

Thrombin (bound to thrombomodulin on the surface of endothelial cells) also slows its own production by creating a separate negative feedback loop. It does this by converting protein C to activated protein C (aPC), a protease that acts as a potent natural anticoagulant. aPC degrades activated factor Va (and activated factor VIIIa, upstream in the coagulation cascade), ultimately reducing thrombin production

Answer 133

There is an increased risk of VTEs with FVL, however it is a very COMMON mutation and most of the mutation carriers do not develop VTE during their life time (only about 5%). Therefore usually prophylactic or lifelong anticoagulation after VTE is not required.

Answer 134

Treat for 4 weeks with anticoagulation when: 1. Thrombus greater than 5cm 2. Thrombus within 5cm of saphenofemoral junction or saphenopopliteal junction 3. Medical risk factors for DVT (eg, prior DVT, thrombophilia, malignancy, estrogen therapy Otherwise treatment is compression, anti-inflammatories, topical agents

Answer 135

1. Warfarin - 5 days prior to surgery (ie, -6 days before surgery date), check INR day before, given vit K 1-2mg if still high. This is based on half life of 36 to 42 hours. Bridge with Clexane only if deemed at very high risk of thromboembolism (recent stroke, mechanical heart valve, CHADS2 score of 5/6). Bridge with Clexane 3 days prior to surgery. Warfarin is restarted within 12-24 hours with bridging Clexane only if high risk of thrombosis. 2. Dabigatran/Rivaroxaban Stopped 2-3 days prior to surgery if normal renal function, or 2-4 days if impaired renal function. Given that peak effect takes place 2-3 hours after dosing, bridging is usually not required. If low bleeding risk post op, start 1 day post surgery If high bleeding risk post up, restart 2-3 days post surgery. If using Clexane bridging, needs to be stopped 24 hours before surgery, based on half life of 3-5 hours. If once a day dosing is used, one-half of the total daily dose is given on the morning of the day before surgery. If twice daily dose is used, the evening dose night before the surgery is omitted.

Answer 136

Reptilase time (RT) is a blood test used to detect heparin contamination. Reptilase, an enzyme found in the venom of Bothrops snakes, has activity similar to thrombin. Unlike thrombin, reptilase is resistant to inhibition by antithrombin III. Thus, the reptilase time is not prolonged in blood samples containing heparin, hirudin, or direct thrombin inhibitors, whereas the thrombin time will be prolonged in these samples. Other causes of prolonged TCTs will not be affected by reptilase time (eg: hypofibrinogenaemia, dysfibrinogenaemia, increased FDP)

Answer 137

Direct thrombin inhibitors - parenteral form

Answer 138

Modified anti-Xa level | PT can also be done but less reliable.

Answer 139

Kappa chains - more are produced, circulates as monomers therefore easily filtered, therefore causes more LCDD and PCT dysfunction Lambda chains - circulates as dimers therefore not as easily filtered, causes more amyloidosis.

Answer 140

Anti-proliferative effect by binding to cereblon and inactivating it

Answer 141

AR or X linked disorder. Congenital malformations exist in 60-70% with café au lait spots, hypopigmentation, abnormal thumbs, microcephaly and short stature, hypogonadism and delayed development. All recognized 15 defects are involved in DNA repair and stabilisation. BM biopsy will show hypocelluar marrow with dysplastic cells. Specific test includes chromosomal fragility in lymphocytes when exposed to DiEpoxybutane (DEB) or Mitomicin C (MMC) Siblings should be tested as there are phenotypic variations. Increased long term risk of complete bone marrow failure, acute leukaemia/MDS, solid cancers. Allogeneic stem cell transplant is curative. Supportive treatments include androgens (oxymethalone) in which anaemia responds the best, transfusion, GCSF.