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CSIM2 > Haem 2.69-2.76 > Flashcards

Haem 2.69-2.76 Flashcards

1
Q

Nail changes in IDA?

A

Koilonychia

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2
Q

Reticulocytes and MCV?

A

Immature red cells; a marker of BM function. Very high levels (reticulocytosis) when red cells are being lost e.g. haemolytic anaemia/bleeding. Larger so push up MCV. May be low in deficiencies or BM failure (chemotherapy, aplastic anaemia)

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3
Q

Four causes of normocytic anaemia?

A

Anaemia of chronic disease (vasculitis, malignancy), renal failure, mixed anaemia, MYELOMA

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4
Q

Ferritin?

A

Low usually diagnostic of IDA; moderate/high less helpful as can just be inflammation. Very high may be haemochromatosis.

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5
Q

TIBC/transferrin?

A

TIBC is indirect measure of transferrin. Blood’s capacity to bind iron. High in pregnancy and IDA to maximise binding; low in anaemia of chronic disease as less transferrin (and more ferritin) produced

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6
Q

Transferrin sat?

A

Normal in anaemia of chronic disease, low in IDA (not enough Fe), low in pregnancy because more transferrin produced

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7
Q

Serum Fe?

A

Highly variable, but low in IDA, low in anaemia of chronic disease (because held IC in ferritin instead), normal in pregnancy

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8
Q

Gene most commonly affected in haemochromatosis?

A

HFE

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9
Q

Features of haemochromatosis?

A

Diabetes (iron stored in B cells), cardiomyopathy, pituitary failure/hypogonadism, arthritis (chondrocalcinosis), bronzed skin, liver cirrhosis

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10
Q

Causes of secondary (aquired) haemochromatosis?

A

Severe chronic haemolysis, multiple frequent blood transfusions, excess dietary iron/parenteral iron

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11
Q

Four causes of “decreased production” anaemia?

A

Haematinics deficiency, anaemia of chronic disease, bone marrow failure, epo deficiency (renal failure)

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12
Q

Two main causes of “increased destruction” anaemia?

A

Haemolysis (AI, sickle cell, G6PD, hereditary spherocytosis), bleeding

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13
Q

Tests when investigating anaemia?

A

FBC (MCV); do haematinics. If normal, may be increased destruction. Do LFTs (increased bilirubin), blood film (reticulocytes/blasts), DAT = direct antiglobulin test; looks for Abs bound to RBCs, haptoglobin levels (low in haemolysis)

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14
Q

What is haptoglobin?

A

Protein that binds to free Hb released from cells. In Intravascular haemolysis, Hb escapes, haptoglobin binds (so levels drop) and then complex removed in spleen, causing splenomegaly.

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15
Q

What is myeloma?

A

Clonal plasma cell neoplasm; produces monoclonal Ab or fragments of Ab.

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16
Q

Features of myeloma?

A

Hypercalcaemia (lytic lesions), renal impairment (Abs deposited in epithelium), anaemia (usually normocytic, renal impairment and BM dysfunction), bony pain (lytic lesions). High risk of cord compression. “CRAB”. Also may see raised ESR, high total protein with normallow albumin, low WCC.

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17
Q

Myeloma pathology?

A

Cytokines lead to increase bone resorption/decreased formation and hypercalcaemia. M proteins/light chains cause renal failure. Deregulated apoptosis/BM invasion/cytokines leads to decreased RBCs/WBCs

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18
Q

Investigating myeloma?

A

Do serum free light chains; see elevation/abnormal ratio. Also do plasma electrophoresis; see monoclonal band at one weight (ie M protein/paraprotein band) and probable reduction in other Ig. Do bone marrow biopsy (clonal plasma cells >10%). Skeletal survery (X-ray/MRI) for lytic lesions. Likely to be rouleaux on blood film (reflects raised ESR)

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19
Q

Actual diagnosis of multiple myeloma?

A
  1. BM biopsy >10% clonal plasma cells
  2. Presence of paraprotein in serum/urine
  3. End organ damage (CRAB).
    Need 3/3.
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20
Q

Most common paraprotein?

A

Mostly IgG, some IgA, rest are light chains only

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21
Q

What are Bence-Jones proteins?

A

Free light chains in the urine; seen in 2/3 multiple myeloma cases

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22
Q

Causes of raised white cells?

A

Reactive, primary marrow problem e.g leukaemia

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23
Q

Considerations in thrombocytopenia?

A

Are they well/unwell, bleeding. Check coag and repeat FBC. NB: clumping on film can be artefact cause of “thrombocytopenia”.

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24
Q

Causes of low platelets?

A
  1. Decreased production (haematinic deficiency, bone marrow failure [leukaemia etc.], rare hereditary causes)
  2. Increased destruction (sepsis, DIC, immune (ITP, TTP, HUS, SLE, APS, hypersplenism))
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25
Q

Causes of thrombocytosis? (Vast majority are acquired)

A
  1. Essential/primary (ET, PV, CML, MF) i.e. myeloproliferative disorders. Can be separatated into Philadelphia +ve (CML) and -ve.
  2. Reactive (infection/inflammation/surgery/IDA, haemorrhage)
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26
Q

Difference between polycythaemia and erythrocytosis?

A

Poly is increased number of red cells; erythrocytosis is increase in red cell mass

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27
Q

Essential thrombocythaemia/cytosis?

A

One of the four myeloproliferative disorders. Isolated rise in platelets. Usually asymptomatic. Exclude reactive cause. Blood film may show megakaryocytes. Test JAK2/MPL/calreticulin; positive is usually enough for diagnosis. If negative, do biopsy (look for AML/primary myelofibrosis).

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28
Q

Treating ET?

A

Aspirin (risk of clotting) +/- cytoreduction with hydroxycarbamide

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29
Q

Investigating polycythaemia?

A

See if primary (myeloproliferative) or secondary (smoking, altitude, epo tumour/injections, sleep apnoea). Do HCT, ferritin, epo, film, JAK2 (+ve in 95% PV).

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30
Q

Polycythaemia vera?

A

Myeloproliferative; primary cause of polycythaemia. JAK2 +ve in 95%. Get itch/sweats/splenomegaly/gout/plethora; risk of CVA/MI/DVT. Raised RBCs and HCT; platelets and WBCs may be elevated. Splenomegaly can be part of diagnostic criteria.

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31
Q

What are the myeloproliferative and lymphoproliferative disorders?

A
  1. Myelo = PV, ET, CML, MF. They are related/may evolve to AML and myelodysplastic syndrome.
  2. Lympho = ALL, CLL, lymphoma, myeloma etc.
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32
Q

Treating polycythaemia vera?

A

Aspirin, VENESECTION is mainstay, mild chemo (hydroxycarbamine)

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33
Q

Key difference between primary and secondary polycythaemia?

A

Epo low in PV (JAK2 allows independence from epo) while high in the others (hypoxia mediated).

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34
Q

High and low Hb?

A

Low = do MCV; high = ferritin, JAK2, epo levels etc. to look for PV.

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35
Q

Primary myelofibrosis?

A

Another myeloproliferative disorder. Present with sweats, splenomegaly, progressive pancytopenias (ie anaemia sx, bleeding, infection) as get proliferation of abnormal cell clone causing replacement of haematopoetic tissue with fibrosis. 5 years life expectancy. Diagnosed on BM biopsy.

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36
Q

Primary vs secondary myelofibrosis?

A

Primary = ‘de novo’; secondary progresses from ET/PV etc.

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37
Q

Why get massive splenomegaly/hepatomegaly in MF?

A

Extramedullary haematopoeisis; occurs in liver/spleen; get abnormal tear-drop poikilocytes.

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38
Q

Treatment of MF?

A

Symptomatic (e.g. splenectomy), cytoreduction, JAK2 inhibitor, HSCT.

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39
Q

Genes linked with MF?

A

JAK2, PML, calreticulin.

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40
Q

CML?

A

Myeloproliferative. Present with raised WCC, symptoms of hepatosplenomegaly, RUQ pain. +/- fever, sweats. Can present with leukostasis (WBC>100); get blurred vision, headaches as cells clump [ischaemia and haemorrhage]. Caused by proliferation of mature granulocytes and their precursors.

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41
Q

Diagnosing CML?

A

Peripheral blood count/appearance, (BM biopsy) and cytogenetics. In peripheral blood, may see low/normal/high platelets, normocytic anaemia, high WCC, early myeloid cells, leukoerythroblastosis. Bone marrow is more to rule out acute leukaemia.

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42
Q

Stages of CML to be diagnosed in?

A
  1. Chronic stage; sweats, weight loss, hepatosplenomegaly but usually asymptomatic.
  2. Accelerated; bleeding, petechiae, ecchymoses; fever (now due to infection not increased metabolism).
  3. Blast phase (like acute leukaemia)
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43
Q

Cause of CML?

A

Translocation of 9:22 chromosomes to give “Philadelphia c’some”; novel gene is BCR-ABL; resulting novel TK causes proliferation.

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44
Q

Treating CML?

A

TKI (imatinib, dasatinib (can cause pleural effusion), PCR monitoring for disease level. Can do HSCT. Very treatable.

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45
Q

Managing IDA?

A

If Hb below ~7, can consider RBC transfusion. Give oral iron or IV iron if more severe. Get constipation and black stool.

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46
Q

Causes of chondrocalcinosis?

A

Gout, pseudogout, hypercalcaemia, Wilson’s, haemochromatosis, osteoarthritis

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47
Q

Investigating haemochromatosis?

A

Transferrin sat %, ferritin (if low ferritin, diagnosis unlikely), genotype (HFE), liver biopsy.

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48
Q

Alcohol and anaemia?

A

Toxic to bone marrow in excess; get fewer, structurally abnormal precursors to RBCs hence macrocytic anaemia. Chronic excess may be linked with folate deficiency “malnutrition of alcohol”; gives megaloblastic red cells and low platelets (myeloid precursors ie also need folate) hence bleeding risk.

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49
Q

Investigating apparent B12 deficient anaemia?

A

Serum B12, Ab to IF (PA). Rx = B12 injection. Could also be low folate although this is less common.

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50
Q

Causes of B12 deficiency?

A
  1. Poor intake (alcohol, vegan diet)
  2. Poor gastric activation (PPI, gastroenteritis)
  3. Poor absorption (coeliac, PA, ileal resection, Crohn;s, chronic diarrhoea).
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51
Q

Baseline bloods in haemorrhage?

A

FBC, group and save, clotting (inc fibrinogen).

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52
Q

What does cryoprecipitate contain?

A

Factor VIII (haemophilia), fibrinogen, factor XIII, vWF. Essentially is concentrate of FFP and is suitable for use as a volume expander.

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53
Q

What is INR a measure of, essentially?

A

PT

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54
Q

Causes of haemolytic anaemia? NB: will often see reticulocytosis to compensate.

A
  1. Intrinsic (hereditary) = hereditary spherocytosis (membrane defect), defective Hb (sickle cell, thalassaemia), defective red cell metabolism (G6PD/pyruvate kinase deficiency), PNH.
  2. Extrinsic (acquired) = immune e.g. AIHA, hypersplenism.
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55
Q

Hereditary spherocytosis?

A

Abnormal red cell membrane; cells are mostly functional but spleen destroys them. Get increased bilirubin (hence pigmented gallstones), increased LDH. Splenectomy is treatment. Get jaundice, HA, splenomegaly, fatigue.

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56
Q

Suspect mixed anaemia?

A

Do red cell distribution width; wide = mixed.

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57
Q

Tumours associated with raised epo?

A

HCC, renal cell carcinoma, haemangioblastoma

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58
Q

COPD and polycythaemia?

A

May be plethoric; indication for home o2.

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59
Q

Platelets in CML?

A

May be high/normal/low; can drop in accelerated phase to give bleeding/petechiae.

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60
Q

Factors in extrinsic pathway?

A

Only VII; vit K dependent hence why warfarin primarily increases PT.

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61
Q

Intrinsic pathway factors?

A

VIII, IX, XI, (XII). APTT.

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62
Q

Vit K dependent factors?

A

10, 9, 7, 2.

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63
Q

Key features of bleeding history?

A

Family history, easy bruising, gum bleeding, prolonged bleeding from minor wounds, menorrhagia/post partum bleeding, post op bleeding/need for transfusion/return to theatre.

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64
Q

Investigating child with haemarthrosis and long APTT?

A

FBC normal. Intrinsic problem. Do correction study (ie mix with normal plasma); if corrects then is factor deficiency. If not then lupus antibody. Do factor assay; here is very low VIII (Haemophilia A).

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65
Q

Severity of haemophilia A?

A

Different mutations can cause it; get different levels of residual active factor VIII. <1% = severe; 1-5% mod; 5-40% = mild.

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66
Q

Significance of low VIII?

A

Not needed for initiation, but key for amplification/propagation so cannot generate stable clot.

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67
Q

Haemophilia A?

A

Most severe bleeding disorder. Usually X-linked recessive (can get mild phenotype in heterozygous girls). Get easy bruising, palpable haematomas. Bleed into weight-bearing joints and muscles; can get degenerative joint disease. Treat with recombinant factor VIII.

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68
Q

Diagnosing haemophilia A?

A

Differentials are haemophilia B and VWD. Diagnosis based on low levels of VIII assay. Genetics help with risk of transmission etc. Expect long APTT with normal PT.

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69
Q

Haemophilia A management?

A

Recombinant FVIII, synthetic ADH (DDAVP) in mild promotes endothelial release of FVIII via VWF, analgesia/physio/immobilisation/education.

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70
Q

Drugs to avoid in Haemophilia A?

A

Aspirin, NSAIDs, heparin.

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71
Q

Haemophilia B?

A

Mutation in factor IX; low levels. Less common than A. AKA Christmas disease. APTT high; PT normal. Do correction study. X linked, recessive. Treat with IV recombinant factor IX; longer t1/2 than VIII so done less frequently. Same presentation.

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72
Q

Transexamic acid in haemophilia?

A

Antifibrinolytic; can be useful for surgery/prophylaxis etc.

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73
Q

VWD?

A

AD inheritance. Low vWF. Present with easy bruising post of bleeding, menorrhagia, mucocutaneous bleeding. Commonest inherited bleeding problem.

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74
Q

Functions of vWF?

A
  1. Binds platelets to subendothelium
  2. Binds platelets to each other
  3. Binds and stabilises FVIII.
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75
Q

Why is APTT long and FVIII low in VWD?

A

vWF binds and transports FVIII!

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76
Q

Investigating VWD?

A

PT normal; APTT may be prolonged. Do VWF assay for quantity and quality! As normal levels present in type 2.

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77
Q

Types of VWD?

A
  1. Mild quantitative defect. Usually asymptomatic. AD
  2. Qualitative defect; can be harder to detect. AD
  3. Severe quantitative defect. AR!
    (Also get acquired and platelet-type [non-hereditary]).
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78
Q

Elevated VWF?

A

Thrombosis risk factor! In TTP, get defect in enzyme that cleaves vWF. Prone to arterial thrombosis.

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79
Q

Treatment of VWD?

A

Desmopressin (DDAVP) triggers vWF release from endothelium; only works in type 1 and 2a. Can give VWF-containing plasma concentrates.

80
Q

Other inherited bleeding disorders?

A

Deficiencies in XI, VII, V, X, XIII; not as severe as VIII and IX. Platelet dysfunction e.g. Glanzmann’s thrombasthenia, Bernard-Soulier syndrome.

81
Q

Acquired haemostatic disorders?

A

DIC, liver disease (reduced factors, dysfibrinogenaemia, thrombocytopenia (due to BM suppression, hypersplenism and low thrombopoietin)), renal, haemorrhagic disease of the newborn (vit K deficiency), drug-related, vit K def.

82
Q

DIC?

A

Balance of haemostasis overwhelmed by massive procoagulant signal. Coagulation becomes systemic. Occurs because (something) damages endothelium and releases tissue factor (starting extrinsic pathway). Low platelets, factors, fibrinogen, high D-dimer. Can present with thrombosis (if microvascular get organ fialure), bleeding, or BOTH.

83
Q

What actually causes tissue ischaemic injury in DIC?

A

Intravascular fibrin deposition; get organ failure.

84
Q

FDPs in DIC?

A

Fibrin degraded products; includes D-dimer. Elevated in DIC.

85
Q

Severity of DIC?

A
  1. Lab evidence of raised FDPs (D-dimer), fibrinogen normal.
  2. Reduced fibrin and platelets, +/- haemostatic signs.
  3. Gross depletion of plt/factors, high FDPs, signs of HAEMOSTATIC FAILURE
86
Q

Diagnosis of DIC?

A

Key DD is severe liver disease. In DIC, get low/ rapidly falling platelets, high FDPs, low fibrinogen (may be normal as is acute reactant), long PT/APTT, schistocytes on peripheral smear, and CHARACTERISTIC HISTORY

87
Q

Conditions associated with DIC?

A

Gram -ve sepsis (endotoxin release exposes TF), trauma, malignancy [acute promyelocytic leukaemia), obstetric (abruption, AFE, fetal death, PET), liver disease, major haemorrhage, incompatible transfusions. Key mediator is TF (starts extrinsic pathway).

88
Q

Treating DIC?

A

Treat cause! Give platelets, cryoprecipitate (if fibrinogen low), FFP (factors), red cells if caused by haemorrhage etc.

89
Q

Causes of pancytopenia?

A

Increased destruction (immune e.g. SLE, sepsis, splenomegaly [mild pancytopenia]) or decreased production (BM failure)

90
Q

Causes of BM failure?

A
  1. Aplastic anaemia
  2. Megaloblastic anaemia
  3. Infiltration with malignancy (haem/non-haem)
  4. Chemotherapy/radiotherapy/viruses/chemicals
91
Q

Which cell lines does pancytopenia involve?

A

Neutrophils, erythrocytes and platelets.

92
Q

What cell lines does BM failure affect?

A

Erythroid, myeloid and megakaryocytic; lymphocytes are usually spared.

93
Q

Investigating BM failure?

A

Haematinics, drug history, reticulocytes (raised in increased destruction), abdo US (splenomegaly).

94
Q

Why do infections look odd in pancytopenia?

A

No neutrophil response! Bacteria enter, spread and kill far more quickly

95
Q

Neutropenic sepsis diagnosis?

A

Neutrophils under 0.5 or under 1 and either a temperature >38 or other signs of infection.

96
Q

Protocol in neutropenic sepsis?

A

FBC, CRP, LFTs, peripheral blood culture (and culture from central line), U&E, lactate. Identify cause. Give tazocin & gentamicin and IVT. Cultures key because hard to find site of origin.

97
Q

Difference between aplastic anaemia and infiltration?

A

BM in aa is hypoplastic; hyperplastic in malignancy.

98
Q

Causes of aplastic anaemia?

A
  1. Congenital
  2. Idiopathic (60%)
  3. Drugs/chemicals (39%) ie benzene, chemotherapy, radiation, sulphonamides.
99
Q

Treating aplastic anaemia?

A

Immunosupression, withdraw cause, HSCT, supportive care e.g. red cells and platelet transfusions.

100
Q

Causes of malignant infiltration of bone marrow?

A
  1. Haem inc. acute leukaemia, myelofibrosis, myeloma, lymphoma infiltration, myelodysplastic syndromes
  2. Non haem e.g. metastatic breast/prostate/thyroid/renal/lung/melanoma.
101
Q

AML and age?

A

Increases with age

102
Q

ALL and age?

A

Peaks in paediatrics; most common childhood cancer.

103
Q

Causes of acute leukaemia?

A
  1. Genetics e.g. Downs; usually no cause found
  2. Haematological disease; any bone marrow disease ie myeloproliferative disease increases risk.
  3. Irradation
  4. Chemicals e.g. chemotherapy is leukaemagenic
104
Q

How do acute leukaemias present?

A

BM failure (pancytopenia), general/constitutional symptoms, tissue infiltration

105
Q

What tissues may acute leukaemias infiltrate?

A

CNS, testes, eyes (anterior chamber), gums (hypertrophic), cutaneous, thymus, nodes. CNS particularly difficult as a sanctuary site in paeds; get nerve palsies etc.

106
Q

Diagnosing acute leukaemias?

A

FBC, clotting, blood film, BM biopsy, tissue biopsy ie LP. On blood film can do IHC (MPO) to differentiate myeloid and lymphoid. Also can do chromosomal analysis etc; has implications for treatment selection and prognosis.

107
Q

Considerations when starting acute leukaemia treatment?

A

Treat infections, transfusions, hydration, sperm/ovary banking, allopurinol, therapy (chemo, intrathecal, transplant). Maintenance therapy longer for boys (3 years) than girls (2 years)

108
Q

Side effects of chemo in acute leukaemia?

A

Nausea and vomiting, bone marrow failure (must remove leukaemia to allow marrow to regrow so balance is fine), hair loss, fatigue, infertility.

109
Q

Prognostic factors in acute leukaemia?

A

Age (younger is better), sex (female better), remission speed (faster better), relapse, blast count, presence of extramedullary disease.

110
Q

Prognosis in AML/ALL?

A

ALL has better prognosis; children have better prognosis.

111
Q

Long term AEs of (childhood) leukaemia and chemotherapy?

A
  1. Short stature
  2. Infertility
  3. Loss of intellect
  4. Lifelong increased cancer risk
  5. Endocrine/cardiac abnormalities
  6. Psychological!
    But most patients are fine.
112
Q

Differences between acute and chronic leukaemias?

A

Acute: cancer cells are undifferentiated blasts (normal appearance in chronic), present with marrow failure in acute (marrow fairly normal in chronic), acute is rapid onset and progression (chronic indolent), acute rapidly fatal if untreated (chronic may not need treatment), patients systemically unwell with acute (rarely in chronic) and need immediate chemo.

113
Q

MAIN cause of BM failure?

A

Malignant infiltration!!!

114
Q

Suspicious sites and size for l’dopathy?

A

Axilla/neck. >6 weeks more worrying; 2 weeks = watch and wait. Groin nodes may be palpable normally. Size >1.5cm.

115
Q

History aspects in lymphoma?

A

Viral screen (HIV and lymphoma risk; HBV because may reactivate in treatment); immunosuppression also independently increases lymphoma risk. Cat contact, travel history, and B SYMPTOMS

116
Q

B symptoms?

A

Weight loss >10%, drenching sweats, fever

117
Q

Exam in lymphoma?

A

Nodes, skin (bruising), neuro (CNS lymphoma/cord compression)

118
Q

CNS lymphoma?

A

Hard to treat (BBB low permeability so need very potent chemotherapy) and can make people unfit for treatment

119
Q

BM and FBC in lymphoma?

A

Usually normal. Biopsy rarely done.

120
Q

Who needs referral for lymphoma?

A

Any patient with a LN >1cm for 6 weeks; any patient with generalised lymphadenopathy ie 2+ non-contiguous areas (DD is HIV seroconversion).

121
Q

Initial investigations in lymphoma?

A

FBC, U&E, LFTs, ESR, monospot, viral screen.

122
Q

Further investigations in lymphoma?

A

Blood film, cell surface markers (e.g. CD20), LDH (high indicates TLS risk or fast growing e.g. Burkett’s), CXR, ferritin, toxoplasma titres, immunoglobulin (exclude myeloma), B2 microglobulin (elevated in lymphoma/myeloma)

123
Q

Biopsy in lymphoma?

A

Key; need architecture, not FNA. Need specialised lymphoma pathologist. Excision node biopsy better than core biopsy. Exact diagnosis essential to choosing correct treatment!

124
Q

What is lymphomatous meningitis?

A

Lymphoma spreading to CNS

125
Q

Reed-Sternberg cells?

A

Owl-eye nuclei; pathognomonic of Hodgkin’s. Binucleate B cell!

126
Q

Diagnosing lymphoma?

A

Biopsy, immunohistochemistry (e.g. CD20), FISH/gene profiling (characteristic translocations etc.).

127
Q

Classic fever in Hodgkin’s?

A

Pel-Ebstein

128
Q

Grade in lymphoma?

A 
High grade (inc Hodgkin's) is fast growing, treat immediately, sick at presentation, but OFTEN CURABLE. Chemo +/- radio.
Low grade is slow, watch and wait, treat when get (B) symptoms but rarely curable.
Essentially, very aggressive NHL will be fatal in weeks if untreated but very curable. NHL can be split into indolent, aggressive and very aggressive; HL also has wide spectrum of disease, mostly curable.
129
Q

Staging in lymphoma?

A

Use CT or PET. Key to determining treatment. Use Anne Arbor.
1. Single region (ie LN and surrounding area)
2. Two separate regions on same side of diaphragm
3. Both sides of diaphragm
4. Diffuse disease (includes an extralymphatic organ e.g. liver, gut, BM, lung nodules).
A/B based on presence of ‘B’ symptoms.

130
Q

Use of PET in lymphoma?

A

More accurate staging than CT but expensive so usually reserved for high grade malignancy.

131
Q

Significance of steroids in lymphoma?

A

Very steroid responsive so extremely useful BUT do not give before diagnosis as makes it hard to obtain accurate histology; particularly for CNS disease. Can also lead to steroid resistance and bugger the haematologist.

132
Q

Follicular lymphoma?

A

Most common; low grade; long natural history. Very slow growing; usually stage 4 at presentation. Stage 1 is rare but can be cured by radiotherapy alone. May transform into high grade NHL.

133
Q

Treating follicular lymphoma?

A

Watch and wait, chemo, steroids, rituximab, HSCT (auto or allo).

134
Q

Autologous HSCT?

A

Harvest own cells, give massive dose of chemo, reinfuse, allows quicker restoration of counts (rather than remaining neutropenic for months)

135
Q

Allogeneic HSCT?

A

Give enough chemo to kill most of BM, then transplant. Remaining lymphoma cells killed by new BM (graft-versus-lymphoma (or leukaemia)). Risks are death (~10%) so only do if have exhausted other options and GVHD (skin, gut, liver)

136
Q

Immunotherapy in lymphoma?

A

Can use naked Ab or conjugate with toxins/drugs. Rituximab is anti-CD20, used in follicular and others. Leads to antibody-dependent cell-mediated cytoxicity (ADCC), complement-dependent cytotoxicity and direct apoptosis. Hugely useful.

137
Q

Diffuse large B cell lymphoma?

A

DLBCL. Rapidly growing, high-grade, NHL. Second most common form of lymphoma. Can evolve from CLL and follicular. Prognosis based on age, number of extra nodal sites, stage, ECOG, LDH (high is bad).

138
Q

Hodgkin’s disease?

A

Bimodal age distribution (15-29, 65-80). See Reed-Sternberg cells (massive inflammation around them).

139
Q

Why is extensive radiotherapy not ideal in young patients e.g. Hodgkin’s?

A

Risk of secondary malignancy

140
Q

Electrolytes in TLS?

A

Raised K+ and urea and phosphate, low calcium. Get cardiac arrest.

141
Q

Why is lymphoma high risk for TLS?

A

All haem malignancies are because their turnover is so high so they are incredibly responsive to chemo. Burkitt’s is fastest growing so higher risk, as is DLBCL.

142
Q

Why might fibrinogen be normal in DIC?

A

Elevated in inflammation

143
Q

Acute leukaemia and grossly abnormal clotting?

A

Acute promyelocytic leukaemia likely; lysis of progenitors produces inflammatory products which give high risk of haemorrhage/thrombosis in first week; if can control then have very good prognosis.

144
Q

Giving platelets in ITP?

A

Not recommended unless actively bleeding (then give extensively) as will just destroy them. Instead, give steroids, rituximab, immunoglobulin.

145
Q

Drug-induced ITP?

A

Heparin is main cause

146
Q

Treatment for refractory ITP?

A

Splenectomy

147
Q

Blood film findings in ITP?

A

May see megakaryocytes as marrow tries to replace platelets

148
Q

Itch and bilateral hilar l’dopathy?

A

Points to Hodgkin’s

149
Q

Differentials for bilateral hilar l’dopathy?

A

Sarcoidosis, HL, NHL, thymic tumour

150
Q

Causes of red cell rouleaux?

A

Anything that raises ESR! Infection, inflammation, malignancy e.g. myeloma.

151
Q

Immediate treatment of myeloma?

A

IV fluids, bisphosphonates, steroids (lowers protein and may save renal function). Stop nephrotoxic drugs

152
Q

Causes of isolated raised PT?

A

Warfarin (affects APTT at higher dose), liver disease, factor VII deficiency (rare), vit K deficiency, lupus anticoagulant (more commonly affects APTT)

153
Q

What pathway does heparin increase first?

A

APTT; PT at higher dose.

154
Q

Things to do in ?cord compression?

A

Exam (inc. bladder percussion/scan), anal tone, perianal sensation, leg power, sensory level. Urgent spinal MRI, steroids.

155
Q

Cancers most likely to cause cord compression?

A

Breast, lung, prostate, lymphoma, myeloma.

156
Q

Causes of infectious mononucleosis?

A

Usually EBV, can be CMV (see owl’s eye).

157
Q

Monospot?

A

Heterophile Ab test; only looks for EBV. Specific but not very sensitive. Follow up for serology for EBV.

158
Q

Cx of mono?

A

Chronic fatigue, splenomegaly and rupture.

159
Q

Ix in mono?

A

Viral screen (HIV/EBV/CMV), toxoplasmosis, LFTs (expect transaminitis), blood film (see lymphocytosis with atypical lymphocytes [appear like monocytes hence name]).

160
Q

Raised APTT alone?

A

Heparin, lupus anticoagulant, inherited deficiency (or acquired inhibition) of VIII, IX, XI, VWD, acquired VWD). Do correction studies, lupus anticoagulant insensitive reagent, factor assays.

161
Q

Management of bleeds on warfarin?

A

INR under 8 = stop warfarin, consider vit K.
INR over 8 = omit, oral vit K.
Minor bleed = omit, oral vit K
Major bleed = omit, IV vit K, consider FFP
Life/limb/sight threatening = omit, IV vit K, beriplex (PCC). Always recheck INR!

162
Q

Risk factors for thrombosis?

A

Cancer (varies according to type), hyperoestrogen (pregnancy/HRT/COC), thrombophilia (inherited; venous), antiphospholipid antibody (arterial and venous), surgery, immobility, air travel, age.

163
Q

Naturally occurring anticoagulants?

A

Activated factors are swiftly deactivated by protein C and S and antithrombin; deficiencies or mutations in these/their binding sites gives clotting tendency.

164
Q

Factor V Leiden FVL?

A

Inherited thrombophilia. Altered binding site on FVa means APC (activated protein C) cannot inactivate it. Thrombosis risk reasonably high in homozygotes and shows synergy with oral contraception etc. Heterozygosity common in North Europeans; may have conferred evolutionary advantage in childbirth.

165
Q

Model of genetic-environmental interaction in thrombosis?

A

With age, get closer to “clotting” threshold; if have inherited thrombophilia hit this @ younger age. Also, one “event” e.g. surgery may be enough to push you over; need multiple in wild type. Illness e.g. cancer, AF can permanently increase risk.

166
Q

Chronic consequences of DVT?

A

Post-phlebitic/thrombotic syndrome; get pain, varicosity, oedema, haemosiderin deposition, ulcers, heaviness, itching.

167
Q

Hospital protocols for DVT prophylaxis?

A

Antiembolic stockings/sleeves (mechanical), early mobility, LMWH (pharmacological thromboprophylaxis).

168
Q

D dimer statistics?

A

Excellent -ve predictive value (high sensitivity) but positive not very useful. A product of fibrin breakdown.

169
Q

Re DVT; if have high pretest probablitity/+ve D dimer?

A

Doppler US; if +ve then decide OPT management or in-house.

170
Q

Where do protein C and S act?

A

FVIII and V (hence role in FVL); S is cofactor. C and S are also vit K dependent, hence why warfarin doesn’t anticoagulate as much as ‘expected’.

171
Q

Why do you need LMWH cover when starting warfarin?

A

Warfarin only acts on synthesis of clotting factors; circulating factors will still be active so need cover.

172
Q

Why does warfarin mainly increase PT?

A

Warfarin acts on 10, 9, 7 and 2; extrinsic contains 7. Will also increase APTT at higher dose. Does not act on 10a (unlike heparin)

173
Q

Heparin and LMWH action?

A

Heparin binds to antithrombin; inactivates 10a, thrombin. Measured by APTT. LMWH inactivates 10a but not thrombin, and cannot accurately be measured by APTT; instead use anti-factor Xa assay. LMWH does not need APTT monitoring, unfractionated does.

174
Q

What does APTT cover?

A

Intrinsic AND common pathways; hence why heparin and LMWH increase it.

175
Q

Direct thrombin inhibitors (dabigatran) and direct Xa inhibitors and PT/APTT?

A

Thrombin inhibitors typically prolong both; may not prolong PT at low levels. Xa prolong both.

176
Q

Starting warfarin protocol (for acute venous thrombosis)?

A

Give LMWH for 5 days or until get two consecutive INRs above 2.

177
Q

Starting xabans for acute venous thrombosis?

A

Loading dose then maintenance.

178
Q

When does bleeding risk increase with INR?

A

Dramatically over 3; therapeutic range usually 2-3

179
Q

Rapid, prompt, slow and ultra slow warfarin reversal?

A

Beriplex (II, IX, X), IV vit K, oral vit K, withhold.

180
Q

Anticoagulant associated ICH?

A

Initially stable; get secondary expansion which must be prevented. Rapid reversal needed to do so, and to allow surgical intervention.

181
Q

Reversing dabigatran?

A

Idarucizumab (takes minutes)

182
Q

Clues to stopping anticoagulation?

A

If had clear precipitant ie surgery then much less likely to recur than spontaneous.

183
Q

DASH score?

A

Likelihood of recurrence of VTE. Higher if high D-dimer (low during anticoag, should be normal after), male, age <50 (as indicates high risk). Hormone associated = reduced risk. 0-1 = consider discontinuing; 2-4 = consider continuing.

184
Q

IDA considerations?

A

TIBC, ferritin, serum iron, transferrin saturation. Exclude coeliac, GI exam and gynae exam!

185
Q

Why are men more affected in haemochromatosis?

A

Run higher levels of iron; many premenopausal women are permanently borderline iron deficient.

186
Q

Investigating end organ damage in haemochromatosis?

A

Liver biopsy, MRI liver and heart, endocrine assessment. Main treatment is venesection.

187
Q

Transfusing old anaemics?

A

Be very wary; easy to overload and cause florid heart failure. Treat cause first.

188
Q

Giving blood before group and save results?

A

Use O- ie universal donor.

189
Q

Final consideration in massive haemorrhage?

A

Blood warming/space blankets; likely to already be hypothermic and cold fluids can further impair clotting.

190
Q

Treatment for hereditary spherocytosis?

A

Can do splenectomy; red cells are functional but swiftly destroyed. Need to counsel family as well.

191
Q

Problem with splenectomy?

A

Become highly susceptible to encapsulated pathogens (Haemophilus, N. meningitidis, particularly pneumococcus) and malaria. Not more likely to get infected but far more likely to die; need vaccines and possibly lifelong penicillin.

192
Q

Why is MCV raised in spherocytosis?

A

Increased red cell turnover causes reticulocytosis (larger cells)

193
Q

Treating relative epo deficiency in renal failure?

A

Epo injections!

194
Q

Things to check in anaemia of chronic disease?

A

Haematinics inc. B12, folate, iron (not just ferritin as likely to be raised in any inflammatory process). Also check U&E, calcium (?myeloma)

195
Q

COPD and headaches?

A

May be secondary polycythaemia. Other causes include altitude, sleep apnoea, epo secreting tumour and epo abuse ie keen amateur cyclists.

CSIM2 (21 decks)

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