Haematology notes Flashcards

1
Q

What is the mutation involved in genetic haemochromatosis?
What is the result of this?

A

HFE gene mutation (HFE =High Fe) which codes for hepcidin
If mutated there is impaired production of hepcidin which causes an upregulation of ferroportin 1 transporter in enterocyte. This causes unopposed absorption of iron in the gut causing increased iron uptake.

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2
Q

Before giving IV iron supplements what must be checked?
What complications of IV iron?

A

IV iron is contraindicated in active sepsis
* Siderophilic organisms that require iron to function will thrive in iron rich enviroment

Complications
* Extravasation of iron when doing IV drip if requires multiple punctures to secure IV line. Dermal level accumulation of iron. Can do saline test to see if there is adjacent swelling post test indicating leakage.

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3
Q

What is the classification for amyloidosis?

A
  • Systemic amyloidosis or localized amyloidosis
  • Acquired or hereditary amyloidosis
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4
Q

What are the types of systemic amyloidosis?

A

**AL amyloidosis **(light chain amyloidosis or primary amyloidosis)
* Light chains of Ig become AL amyloid protien
* Etiology: plasma cell dyscrasias (e.g. multiple myeloma)
* Typically affects the heart, kidney, tongue, peripheral and autonomic nervous system, GIT. Rapidly progressive clinical course
AA amyloidosis (reactive amyloidosis or secondary amyloidosis)
* Serum amyloid associated protein (SAA) becomes AA amyloid protein
* Etiology: chronic inflammatory conditons (e.g. IBD, RA, SLE), chronic infections (e.g. TB, osteomyelitis), RCC, lymphomas
* May occur at any age: most common in children. Typically affects the kidney, liver and spleen, GIT, adrenal glands.
* Disease progression can be slowed by managing the underlying condition
AB2M amyloidosis (B2 microglobulin amyloidosis or haemodialysis associated amyloidosis)
* B2 microglobulin becomes AB2M amyloid protein
* Etiology: long term haemodialysis, end stage renal disease
* Features: develops 10 years after starting. Typically affects joints and tendons, manifesting with scapulohumeral periarthritis, carpal tunnel syndrome, bone cysts
ATTRmt amyloidosis (mutated transthyretin amyloidosis, ATTRv (variant) amyloidosis, or hereditary transthyretin amyloidosis)
* Transthyretin is mutated transthyretin (ATTR): autosomal dominant disease
* Familial amyloid cardiomyopathy: typical age of onset: >60 years. Affects endomyocardium
* Familial amyloid polyneuropathy. Typical age of onset: >20 years, affects peripheral and autonomic nerves
ATTRwt amyloidoisis (wild type transthyretin amyloidosis or senil cardiac amyloidosis
* Normal transthyretin (ATTRwt) –> deposition in cardiac ventricles –> cardiac dysfunction (less drastic than in AL amyloidosis
* Median age of dx is 75 years. Typically affects the heart, ligaemnts and tendons, peripheral nerves

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5
Q

Approach to make dx of amyloidosis?

A

Tissue sample: target organ (kidney/nerve) preffered in patients with single organ involvement. Abd fat inspiration or rectal mucosa preferred in patients with multiorgan and/or tissue involvement

Methods
* Congo red stain to confirm amyloid deposition
* Histology shows apple-green birefringence under polarized light
* Additional findings from an affected kidney may include deposits in glomerular mesangial areas and enlarged tubular basement membranes that can be identified via light microscopy.

Gold standard is mass spectrometry
IHC light chain (if demonstrated can indicate AL amyloidosis)

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6
Q

What is the etiology of AL amyloidosis?
What pathophysiology
What clinical features?

A

Etiology: low level expansion of a plasma cell dyscrasia (e.g. multiple myeloma, Waldenstrom macroglobulinemia)
Patho: increased production of the light chains of immunoglobulins –> deposition of amyloid light chain protein A(L) in various organs

Clinical features
* Skin: cutaneous ecchymoses around the eyes (raccoon eyes), combined with yellow waxy papules
* Heart: restrictive cardiomyopathy, HFpEF, AV block
* Kidney: nephrotic syndrome, type 2 RTA, nephrogenic DI
* Tongue: macroglossia (specific to AL amyloidosis): OSA
* ANS: autonomic neuropathy
* GIT: malabsorption, hepatomegaly
* Haematopoietic system: bleeding disorders, splenomegaly
* Musculoskeletal system: carpal tunnel syndrome (may be bilateral), shoulder pad sign

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7
Q

What are the diagnostic Ix for AL amyloidosis and its management

A

Tissue biopsy
Assessment of organ involvement, including ECG, cardiac imaging
Obtains diagnostics for plasma cell dyscrasias to identify the underlying cause
* Serum electrophoresis: monoclonal gammopathy
* Urine protien electrophoresis (UPEP) with immunofixation: Bence-Jones proteins

Suspect AL amyloidosis in patients with multiple affected organs (heart failure with preserved ejection fraction, nephrotic range protienuria, peripheral neuropathy, hepatomegaly and/or noninfectious diarrhea), and/or atypical MGUS or smoldering multiple myeloma

Management
Control of underlying plasma cell dyscrasia with chemotherapy eg. melphalan + corticosteroids, thalidomide, bortezomib

Rapidly progressive clinical course if left untreated
Median survival time without treatment is 1-2 years

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8
Q

What is the etiology of AA amyloidosis?
Pathophysiology?
Clinical features?

A

AA amyloidosis is secondary to a chronic disease, such as:
* Chronic inflammatory conditions (e.g., IBD, rheumatoid arthritis, SLE, vasculitis, familial Mediterranean fever)
* Chronic infectious diseases (e.g., tuberculosis, bronchiectasis, leprosy, osteomyelitis)
* Malignancy (e.g., renal cell carcinoma, lymphomas)

Pathophysiology
Chronic inflammatory process → ↑ production of acute phase reactant SAA (serum amyloid-associated protein) → deposition of AA (amyloid-associated) protein in various organs

Clinical features
* Kidney: nephrotic syndrome, type II renal tubular acidosis, nephrogenic diabetes insipidus
* Adrenal glands: primary adrenal insufficiency
* Liver and spleen: hepatomegaly, splenomegaly
* Gastrointestinal tract: malabsorption
* Heart (rare): severe thickening of ventricular wall

Main feature of AA amyloidosis at dx is renal dysfunction (CKD, nephrotic syndrome). Cardiac involvement is rare.

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9
Q

What are the dx tests for AA amyloidosis and management?

A

Kidney tissue biopsy findings
* Global and segmental amyloid deposition
* Diffuse and/or focal glomerular involvement
* Enlargement of glomeruli
* Tubular atrophy
* Interstitial fibrosis

Assessment of organ involvement, including BMP, estimated GFR, urinalysis
For suspected cardiac involvement: multiparametric CMR (including late gadolinium enhancement imaging)

Identify the underlying inflammatory disosrder (if not yet known) consider: CXR, inflammatory markers (ESR, CRP)

Managaement
Treat the underlying condition to reduce AA production (mainstay of treatment) e.g. colchicine for FMF
Provide supportive care for associated complications (CKD)

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10
Q

What are the clinical phenotypes of ATTRmt amyloidosis, etiology and the affected sites?

A
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11
Q

What are the types of localized amyloidosis and organs affected?

A
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12
Q

What nuclear imaging used to assess severity of cardiac amyloidosis?

A

Tc-99m PYP (pyrophosphate) nuclear scan is useful for transthyretin amyloid (ATTR). Not useful for AL amyloidosis.

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13
Q

What amyloidosis associated with haemodialysis patients?
What clinical features may there be?

A

AB2M amyloidosis (B2 microglobulin)
Will accumulate amyloid protiens (misfolded proteins) that mainly deposit in the joints
May manifest as carpal tunnel syndrome

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14
Q

What are the general principles of management of sarcoidosis?
If there is heart involvement how does this affect prognosis?

A

Drugs used to stop the production of amyloid proteins.

If there is extensive adherence of proteins to the heart with heart failure –> difficulty in the amyloid protien disolving away from the organ.

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15
Q

What are the 2 types of transthyretin in amyloidosis?

A

Hereditary (hATTR-CM) and wild type (wATTR-CM) which is acquired

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16
Q

What is the initial Ix if suspicious of lymphoma?

A

PBS for lymphocytosis. If looks abnormal do flow cytometry (immunophenotype). If CD antigens are present it is clonal B cell in circulation (T cell is less common)
Can do light chain restriction
Or Ig rearrangement to prove those B cells are clonal

Plasma cell disorders will 90% elevated lambda chain, only 10% is kappa

If positive in peripheral blood –> already stage 4 lymphoma (as in systemic circulation)

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17
Q

How do you work up a patient with thrombocytosis?

A

Work up to rule out secondary thrombosis
* CXR (rule out CA lung)
* CEA +/-colonoscopy (rule out CA colon)
* CRP, ESR (underlying inflammation)
Wont do rheumatic work up (as expensive)

Causes of secondary thrombocytosis: infection, inflammation, malignancy, iron deficiency anemia)

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18
Q

How to do the workup for suspected PV?

A
  • Peripheral blood do JAK2V617F (cytogenetics). If present in the blood does not require bone marrow biopsy –> indicates that its clonal (carries the same mutation)
  • Minority of case (10%) without JAK2 V617F requires bone marrow biopsy: must do CALR exon 12

Used to rule out prefibrotic PMF or ET

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19
Q

What are the causes of reversed albumin: globulin ratio?

A
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20
Q

What are the causes for increased albumin/globulin ratio?

A

Not common and should raise suspicion in paeds

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21
Q

Patient with mechanical heart valve leak presents with leukopenia + increased LDH and urate (elevated to four digits). What could be the cause?

A

Valve related haemolysis
ITP

MUST RULE OUT HAEM MALIGNANCY since urate and LDH should not be this high

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22
Q

What Ix should be done and in what order for persistent lymphocytosis?

A
  • PBS first to assess morphology (is there dysfunctional/morphological issue)
  • Flow cytometry (protein expression on cells) to determine clonality (CD5 on T cell is less common: if its high most likely clonality). Can see light chain expression (kappa or lambda restricted than it is more compatible with clonal)
  • IgH gene rerrangement and TCR gene rearrangement using PCR (peripheral blood of bone marrow aspirate): should have lots of variation in VDJ rearrangement and T cell receptors (shows functional immune system)

If clonal abnormality than do FISH (for prognosis not for proving clonal)
At this stage the diagnosis of clonality is already made. If it is leukemia than it necessitates bone marrow biopsy aspirate and trephine biopsy to confirm.

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23
Q

Why is chromosome 17p deletion bad prognosis for CLL?

A
  • Short head of chromosome 17 contains TP53 tumor suppressor gene (any strain breaks will repair). If absent does not know how to do apoptosis.
  • Will not respond to chemotherapy. As chemotherapy induces DNA breaks. So even if there is DNA breaks there is no apoptosis.
  • Hence other therapy such as venetoclax which is a bcl2 inhibitor which activates BAK and BAX proteins which increases mitochondrial outer membrane permeabilization (MOMP) and induces apoptosis (bypasses cells inability to induce apoptosis by itself)
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24
Q

ddx for increased lymphocytosis?

A
  • Chronic NK lymphocytosis
  • Monoclonal B cell lymphocytosis
  • Early phase HIV
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25
Q

Can leukostasis occur in CML?

A

Not really as CML has more mature cells hence its shape is adaptable. Even if bigger due to its adjustable shape it won’t have leukostasis.

Blasts more than 100 even if AML has high chance of leukostasis

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26
Q

What is a simple PE to check for hyperviscosity?

A

Can look at retina for engorged vessels and swollen disc (indicates microcirculation is impaired)

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27
Q

What does bone marrow aspirate vs trephine biopsy show?

A

Bone marrow aspirate = morphology
Trephine biopsy: cytology (architecture of bone marrow: to determine status of haematopoiesis: if hypo or hypercellular)

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28
Q

What is MDS cell count normally?

A
  • MDS is the precursor lesion of acute leukemia
  • Rate of progression to AML depends on lineage as it will definitely transform to leukemia given time
  • Red cell/white cell/megakaryocytic lineage

More likely to cytopenic (gene defect): ineffective and earlier apoptosis (can be hyperproliferative but immature and doesn’t progress)

Can even have MDS/MPN overlap if both high cell count and dysplasia

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29
Q

What is the criteria for POEM syndrome?

A
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30
Q

What is the monoclonal gammopathy of renal significance?

A

Monoclonal Ig deposition but does not meet the CRAB criteria for MM (renal insufficiency is classified as creatinine clearance <40ml/min)

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31
Q

If IgGAM is low in suspected mutiple myeloma what may patient have?
How to can acute renal failure affect SPE?

A

Light chain myeloma

In acute renal failure may not be able to detect light chains in blood as all excreted out in kidney –> hence a comprehensive investigation would also include urine protein electrophoresis (not just SPE)

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32
Q

Lymphoma patient, what is seen and dx?

A

Dilated lateral ventricles
Normal 4th ventricle

Hence this is communicating hydrocephalus due to leptomeninges metastasis of lymphoma which is causing impaired reabsorption of CSF

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33
Q

What is management of TTP?

A

ADAMTS13 mutation

Tx
* Steroid
* Azathioprine
* Plasmapharesis

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34
Q

Mx of CMV retinitis and if resistant what drug?

A
  • Initial is IV valganciclovir
  • If resistant gene on bacteria give Foscarnet
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35
Q

Haematological changes in SLE?

A

Macrophage activation syndrome refers to haemophagocytic lymphohistiocytosis (HLH) that associates with an autoimmune disease. Inflammatory reaction due to cytokine storms provided by massive dysregulation of macrophage lymphocyte interactions –> stills disease and kawasaki disease

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36
Q

When may aspirin be used in procedures?

A
  • Dental procedure
  • Endoscopies with biopsies and polypectomyies
  • Opthalmologic procedures
  • Peripheral vascular proceure
  • Neuraxial anesthesia

Warfarin can be continued for most dental procedures if INR is kept at a lower range before the procdure and close monitoring.

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37
Q

When to stop anticoagulants for periop management?

A

In minor dental procedure stop warfarin 2-3 days before procedure

If major surgery/high risk of thrombosis: stop warfarin therapy 5 days before surgery.
Resume warfarin 12-24 hours after surgery when there is adequate haemostasis.

If high risk for thrombosis consider bridging therapy with UFH (used in renal impairment) or LMWH (more effective)
Those recieving bridging therapy with UFH, stop 4-6 hours before surgery. For LMWH stop 24 hours before surgery.

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38
Q

Perioperative management of antiplatelet therapy in patients with coronary artery disease

A
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39
Q

Acute and long term anticoagulant for DVT management

A

Indications for anticoagulation: only in proximal DVRT and PE

Cancer patients: prefer LMWH over warfarin
Pregnancy: hypercoagulable state: switch to LMWH when 1st trim and >36w –> cover up to 6w postpartum
HIT: heparin C/I: start parenteral non heparin anticoagulants –> bridge to warfarin
APL: heparin followed by indefinitive warfarin (preferred over DOAC)

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40
Q

Early and late complications of HSCT

A
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41
Q

Infections during recovery from HSCT and mx

A
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42
Q

Infections causing haemolysis

A
  • Respiratory: mcyoplasma pneumoniae infection
  • Malaria, C. perfringens
  • EBV
43
Q

What tumors are prone to tumor lysis syndrome?

A
  • High grade lymphomas (Burkett, DLBCL, aggressive non Hodgkins lymphoma)
  • ALL (children)
  • AML (adults)
  • High proliferation rate
  • Chemosensitivity of malignancy
  • Large tumor burden
44
Q

Patient with lymphoma had hip replacement, cause?

A
  • Hx of lymphoma, likely had steroids –> AVN
  • Degenerative(OA hip)
45
Q

What anticoagulants?

A
  • Warfarin: anti vit K antagonist (special diet and monitoring INR) –> inhibits F2,7,9,10 production
  • DOACS: direct thrombin inhibitor (dabigatran –> has antidote: idarucizumab), F10a inhibitors (apixaban, rivaroxaban)

Dabigatran (C/I if the creatinine clearance <30ml/min), apixiban and rivaroxaban <15ml/min

46
Q

Indications for using anticoagulants to prevent thrombosis?

A
  • Malignancy (50% cause of thrombosis)
  • NSTEMI/STEMI
  • Mechanical heart valve
  • Moderate to severe MS with AF
  • Prevention after major surgery (esp prior to ortho)
47
Q

How is heparin administered?

A

LMWH only can do SC
UFH mostly IV

48
Q

What are the clinical situations for subcutaneaous heparin?

A
  • DVT prophylaxis
  • Treatment of DVT
  • Pulmonary embolism prophylaxis (pre op)
  • Unstable angina and NSTEMI
  • Bridging therapy
  • In ICU (serious medical illness and immobilised for long period)
49
Q

What is the difference in heparin for treating and preventing DVT?

A

Dosage of SC LMWH is different
Frequency different: LMWH have to be given twice daily for treatment (enoxaparin), once daily for prophylaxis

50
Q

Complications of heparin and how to check?

A
  • Bleeding
  • Heparin induced thrombocytopenia (immune induced): CBC and test for heparin platelet factor 4 (PF4) ELISA

Mx of HIT: stop heparin and replace with alternative anticoagulant. Treat for at least 48 hours and until platelet count has recovered.

51
Q

MoA of warfarin?

A
  • Vit K is a cofactor for the carboxylation of specific glutamic acid groups in a coagulation factors 2,7,9,10. During this step vit K is oxidized to vit 2,3 epoxide. The regeneration of vit K (reduction) by vit K 2,3 epoxide reductase is inhibited by warfarin.
  • Do not have a supply of reduced vit K to produce coagulation factors
52
Q

Why use INR?

A

Ratio between patients PT and controlled PT in lab normalized to a ratio
PT will vary between labs depending on reagant used

53
Q

What is normal INR range?
When to aim for higher or lower INR?

A

INR normal range: 2-3

Aim for higher INR when there is higher risk of thrombosis
Aim for lower INR when lower risk of thrombosis: INR of 2

Only indication of warfarin now is mechanical heart valve

54
Q

Before administering warfarin what must be checked?
How to manage overwarfarinization?

A

Check other drugs for drug interaction

Overwarfarinization
* Stop warfarin
* Replace coagulation factors using FFP (gradually reduce INR)
* IV vit K (do not want to instantly normalize INR –> thrombosis of heart valve)??

55
Q

What DOACs are there and adv?

A

Anti F2a (thrombin): dabigatran
Anti F10a: apixaban, edoxaban, rivaroxaban

Adv: no need INR monitoring, no need to change diet, no need to worry about drug interaction

56
Q

How to manage overdose of DOAC?

A

Dabigatran: antidote is idarucizumab
Rivaroxaban, apixiban and edoxaban: andexanet alfa

57
Q

When to stop DOACs prior to surgery?

A

DOACs are short acting and eliminated by kidney (renal function will influence when to stop)
Dosage of apixiban: taken twice daily (can stop 12 hours before minor operation)
Rivaroxaban (taken once daily) can stop 24 hours before

If minor operation: 24 hours is normally sufficient
If major operation: stop DOAC even longer (ensure normal coagulation)

58
Q

Which DOACs can be reversed by dialysis?

A
  • Dabigatran can be removed by dialysis as it is not protein bound
  • Rivaroxaban, apixiban and edoxaban is protein bound so cannot be removed by dialysis
59
Q

Bleeding manifestation in antiplatelet

A

Bruises (people on anticoagulants do not bruise frequently): minor trauma (which platelets normally take care of)
If aspirin and head trauma (not that worried about subdural haematoma)(

60
Q

Anticoagulant bleeding manifestation

A
  • Nasal bleeding, epistasix
  • Subdural haematoma
  • Intracerebral hemorhage
  • GIB
61
Q

What is the most common cause of AF?

A
  • Old age, IHD –> AF is a degenerative disease
  • Old peopl with AF taking DOACs
62
Q

Chemo for DLBCL

A

RCHOP
R: rituximab
C: cyclophosphamide (alkylating agent)
H: hydroxydaunorubicin = doxorubicin (anthracycline = check ECG and echocardiogram)
O: oncovin=vincristine (vinca alkaloids)
P=prednisolone

63
Q

Which type of NHL presents with generalized lymphadenopathy?

A
  • Low grade because the clinical course is slow that when the patient discovered it may already be spreading to other lymph nodes
64
Q

What is ann arbor staging?
What staging can be done in PE?

A

Stage 1 (one LN region or lymphoid structure) and stage 4 (involvement of extranodal sites

65
Q

What are the components of metabolic syndrome?

A
  • HTN ≥135/80mmHg or on anti-HTN
  • IFG ≥5.6mmol/L or on DM medications
  • hypertriglyceridemia TG>1.7mmol/L or on triglyceride-lowering tx
  • ↓HDL – M: <1mmol/L; F: <1.3mmol/L or on tx for low HDL
  • abdominal obesity – WC>90cm for M, >80cm for F
66
Q

Define neutropenic fever?
What is Tx?
What is the sepsis workup?

A

Neutropenia: ANC <0.5 x10^9/L

Tx (within 1 hour of presentation after immediate sepsis workup)
Covers gram positive cocci and gram negative bacilli with antipseudomonal coverage (especially ESBL (extended spectrum B lactamase) producing organisms)
* Piperacillin tazobactam (tazocin)
* Carbapenems (meropenem): 1gm q8h IVI
* Cefipime

Antifungal agents if persistent fever after 4-7 days of broad spectrum antibacterial regimen and no identified fever source.

Sepsis workup
* Complete history and PE to identify infectious focu
* Blood cultures (set collected from each lumen simultaneosuly if CVC present and 1 peripheral site), other cultues e.g. urine, sputum, respiratory virus panels, CSF, stool etc if clinically indicated

67
Q

Types of lymphoma?

A
  • Hodgkin lymphoma (reed sternberg cells) and non hodgkin lymphoma
  • Non hodgkin lymphoma divided into low grade and high grade and different lineages
  • Can be differentiated by immunophenotyping. B cell: CD19,23, T cell: CD3,4 and 8, NK cell: CD16, CD56.

Classical hodgkin lymphoma
Classical: nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted.
Nodular lymphocyte predominant HL

Non hodgkin lymphoma
Grade: low grade (follicular lymphoma, SLL), intermediate grade (DLBCL), high grade (burkitt lymphoma, lymphoblastic lymphoma (LBL))

68
Q

meropenem class of drug and moa
spectrum coverage?

A
  • carbapenem (B lactam) that has bactericidal action by binding to penicillin binding proteins in the bacterial cell wall and inhibiting peptiglycan cross linking associated with cell wall synthesis leading to cell death.
  • Coverage: gram negative, gram postivie and anaerobic bacteria
69
Q

What are the agents used in AML?

A
  • Induction followed by consolidation
  • Induction = 73CD cytarabine 7 days + daunorubicin 3 days
  • Consolidation depends on response to inductio nand risk
    If complete remission+ favorable risk –> chemo e.g. high dose cytarabine. Poor risk –> allo-HSCT
    Complete remission-ve –> redincue w/ alternative –> MEC (mitoxantrone, etoposide, cytarabine), high dose cytarabine

Relapse after CR+ –> salvage chemo or clinicaltrial –> allogenic HSCT

70
Q

Drugs that may cause chemotherapy induced alopecia

A
71
Q

What to expect to see in the fundus of a person with acute leukemia?
What is this syndrome called?

A

Leukemic retinopathy: hyperviscosity –> retinal vein tortuisity and dilatation.
Direct infiltration with retinal greyish white nodules, perivascular sheathing, roth spots, white centered retinal hemorrhages

There would be occlusion of retinal veins causing venous engorgement –> than central retinal vein occlusion
Hyperviscosity syndrome

72
Q

Clinical features of hyperviscosity syndrome

A
73
Q

What are the causes of pancytopenia?

A

Decreased production
* Primary
* Secondary: CT (myelosuppression), RT, DRUGS (sulfonamides, antithyroid drugs, thiazides, NSAIDs, colchicine), viruses (hep, HIV, EBV, parvovoirus B19). Immune: SLE, GVHD, post HSCT
* Infiltration: primary malignancy (acute leukemias, MPN, MDS, MM)

Increased destruction
* Hypersplenism: most commonly secondary to pulmonary hypertension due to cirrhosis
* DIC
* AI mediated cytopenias

74
Q

Reversible causes of pancytopenia

A
  • Drugs most common (esp TCM herbs)
  • Infection
  • Viral
75
Q

Causes of aplastic anemia?

A
  • Autoimmune, viral (HIV, HCV, parvovirus B19)
  • Chemicals, radiation exposure
  • Drugs: anticonvulsants, antithyroid medication, cytotoxic drugs, chloramphenicol
  • Fanconi anemia, if with family history
76
Q

How to differentiate MDS and AML in peripherael blood and bone marow?

A

MDS: peripheral blood (cytopenia: cells undergo premature death), bone marrow (myelodysplasia and <20% myeloblasts)
AML: peripheral blood (leukocytosis), bone marrow (>20% myeloblasts)

77
Q

Infective causes of rash

A
  • HIV, EBV
  • CMV/HSV/VZV: generalized only in immunocompromised px
  • Viral exanthems in childhood: measles, rubella, parvovirus B19 (erythema infectiousm), HHV6/7 (roseola infantum)
  • Bacerial: meningococcemia (generalized petechial rash)
78
Q

autoimmune causes of generalized rash

A
  • JIA
  • Kasaki disease in children
  • CTD: SLE (ACLE or CCLE (sp discoid) can present in a generalized photosensitive distribution. DM: photosensitive distirbution (v sign, shawl sign, heliotropic rash)
  • Vasculitis
79
Q

Drugs causing generalized rash

A
  • Common: B lactams (esp penicillins, cephalosporins)
  • macrolides
  • Fluoroquinolones
  • Anti TB
  • Cotrimoxazole
  • AEDs (CBZ, PHT()
  • NSAIDs
  • Paracetamol
80
Q

Rash of SLE presentation

A

Acute cutaneous lupus erythematosus
* Localized, generalized or TEN like eruption –> classic butterfly malar rash w erythema over the cheeks and bridge of the nose sparing the nasolabial fold

Subacute cutaneous lupus erthematosus: psoriasiform (ddx: psorasis, discoid eczema) or annular (ddx dermatophytosis, sp tinea corporis) erythematous plaques usu on the shoulders, forearms, neck or upper torso. Strongly assoc with a/w anti Ro

Chronic cutaneous lupus erythematosus
Erythametous scaly plaques that exhibit follicular plugging and heal w/ scarring. Occurs on the neck, scalp and ears. Has a generalized variant which involves trunk or extremities

81
Q

How to Mx thrombocytopenia?

A

Platelet transfusion

ITP treated by immunomodulation
* Initial episode: steroid (1st line) + immunosuppressants (2nd line) +IVIG
* Refractory episoddes: thrombopoitein receptor agonists (PO eltrombopag, SC romiplostim)

82
Q

Causes of renal impairment in multiple myeloma?

A
  • HyperCa: renal vasoconstriction and hypovolemia –> prerenal failure. Also nephrolithiasis, nephrocalcinosis (post renal obstruction)
  • Paraproteinemia –> light chain cast nephropathy (mmore common): can cause proteinuria/ nephrotic sydnrome but this isnt AKI as it doesnt result in decreased eGFR in most cases
  • Hyperuricemia: uric acid nephropathy
  • Hyperviscosity (do fundoscopy to look for retinal vein engorgement, CRVO or arterial occlusions (roth spot) due to paraproteinemia
  • Drug induced always (if just had flu –> NSAID (helps with fever)). The flu can also present with diarrhea and vomiting causing hypovolemia (prerenal cause)
  • Dehydration: hypercalcemia induces autophagocytosis of AQP2 causing nephrogenic DI
83
Q

How does NSAID cause damage to kidneys?

A
  • Inhibits prostaglandin formation therefore there is constriction of afferent arteriole which reduces perfusion of glomerulus and reduces eGFR
  • Acute interstitial nephritis is an immunological reaction after NSAID exposure for a week due to inflammatory cell infiltrate in the interstitium of the kidney.
84
Q

Indications for renal replacement therapy (AEIOU)?

A
  • Acidosis pH<7.1
  • Electrolytes: hyperK >6.5mmol/L or ECG chcanges
  • Intoxication: drugs
  • Overload of fluid refractory to diuretics
  • Uremic sx most notably uremic encephalopathy and bleeding
85
Q

SOB and AKI with multiple myeloma causes?
Is diuretics useful if the SOB is due to fluid overload?

A
  • Most likely is fluid overload –> pulmonary edema +/- pleural effusion
  • Pulmonary infection (CAP, oppurtunistic) –> septic shock –> prerenal AKI
  • Vasculitis process affecting kidneys and lungs e.g. goodpasture syndrome, ANCA associated vasculitis

The effectiveness of diuretics are a function of their concentration in the tubules, meaning that have to prescribe a higher dose for AKI patients to achieve same effects.
However there is higher risk of causing otoxicity

86
Q

Mx of hyperK (acute and definitive)

A

Temporizing methods to avoid cardiac complications
* Haemodynamically unstable: IV 10% calcium gluconate 30ml over 2-3 mins with cardiac monitoring If haemodynamically stable give over 1 hour (rapid onset in 1-3 min; but short term duation of 30-60 min) –> used to buy tome
* 8-10 units of Regular human insulin (actrapid HM) with 250ml D10 or 50ml D50 over 30-60 mins (onset: 30 mins, duration 40-60 mins)
* NaHCO3 8.4% 100-150ml only if pH<7 done in separate IV line –> watch out for fluid overload.

Definitive methods wihch actually decrease total K
* RRT if acute (thresholds are K >6.5mmol/L (alarming) and ECG changes (peaked T waves etc)
* K restriction, exchange resins (e.g. resonium A) and diuretics (furosemide)

87
Q

If K is 5 how to manage?

A
  • can adjust K more slowly via IV 10% calcium gluconate 30ml but over 1 hour (instead of 3-5 mins)
  • Cation exchange resin: resonium A
  • Loop diuretics: furosemide
  • IV insulin/dextrose
  • Low K diet
88
Q

If overnormalize INR what to do?

A

Requires anticoagulant coverage (as indication for warfarin is only mechanical valve now): so give LMWH until INR is back in therapeutic range

89
Q

```

~~~

INR is 5 reason?
What is warfarin diet?

A

Drug food interaction: alcohol, change to low vit K diet
Drug drug interaction: amiodarone, antibiotics (ciprofloxacin, septrin, metronidazole, isoniazid)

Avoid green leaf vegetables

90
Q

How to confirm the dx of HHT?

A

Curacao criteria (3/4 is definite HHT)
* Spontaneous recurrent epistaxis
* Multiple telangiectasias in typical locations (skin, oral cavity, GIT)
* Proven visceral AVM (lung, brain, liver)
* 1st degree family affected

Haemoptysis –> lung AVM

91
Q

What organs affected in long term iron tranfusion

A
  • Dilatsed cardiomyopathy, hepatomegaly, splenomegaly
  • pancreatic – DM
  • endocrinopathies – pituitary/gonadal involvement → hypogonadism (assess gonadal toxicity, preimplantation genetic diagnosis for thalassemia), GH deficiency; also hypothyroidism, hypoparathyroidism
  • derm – bronze hyperpigmentation due to hemosiderosis
  • joint – arthropathy esp involving the 2nd/3rd MCPJ and often w/ chondrocalcinosis
  • (also susceptibility to ferrophilic organisms, eg Klebsiella, Y. enterocolitica,
92
Q

What is used to monitor severity of iron overload on heart?
What iron chelator is SC?

A

T2W MRI as although higher ferritin levels are a/w higher organ Fe (the correlation is not acccurate)

Deferoxamine SC

93
Q

Where is LDH found in cell?
Function?

A
  • Cytoplasm
  • LDH converts lactate to pyruate in an anaerobic reaction
94
Q

Length of anticoagulation use post DVT?

A

short-term anticoagulation (3–6m):
* 1st episode proximal VTE (provoked or unprovoked)
* PE due to reversible/time-limited risk fc
* distal DVT
extended anticoagulation 6–12m for certain px:
* phlegmasia cerulea dolens
* persisting but reversible risk fc
indefinite anticoagulation:
2nd episode proximal VTE
* recurrent PE
* active CA (or until cured)

95
Q

What to expect to see in PBS for MDS?

A

MDS – need ≥10% dysplastic cells of multiple lineages:
* RBC – oval macrocytes, Howell–Jolly bodies, ring sideroblasts
* WBC – pseudo-Pelger–Huët anomaly (hyposegmented NE, def as <3 segmentations; cf megaloblastic anemia)
* PLT – giant PLT
absence or <20% blasts (need to r/o AML)

96
Q

Elderly patietn with pancytopenia and macrocytic RBC what can be the cause?

A
  • Megaloblastic anemia
  • MDS: MCV may be normal or raised (increased RDW reflecting variability in RBC size)
97
Q

Tx of MDS?

A

Azacitidine: pyrimidine nucleoside analog of cytidine which causes direct cytotoxicity on abnormal bone marrow HSCs

98
Q

AE of HSCT

A
  • Oppurtunistic infection
  • SE of conditioning therapy (eradicate the haematologic malignancy in case of malignant indication for HSCT): involves chemo/radio/immunotherapy
  • GvHD (acute/chronic)
99
Q

Mechanism of CART

A
  • Extract patient’s autologous T cells
  • Modify T cell receptors (e.g. TCR) for tumour antigen recognition without MHC presentation or co-stimulatory signal
  • Reinfuse the now-activated T cells back into the patient
100
Q

Complications of CAR-T therapy

A
  • Cytokine release syndrome: fever, shock due to proliferation of CAR-T cells. Tx: anti IL6 (tocilizumab), steroids
  • CAR-T cell related encephalopathy syndrome (CRES): delirium due to CAR T cells in the brain causing cerebral edema. Tx: steroids, antiepileptics e.g. lorazepam
  • Haemophagocytic lymphohistiocytosis
101
Q

Common AE of platinum based chemo drugs

A
  • Peripheral neuropathy in glove and stocking distribution
  • Ototoxicity: tinnitus, hearing loss
  • Nephrotoxicity: proximal tubule injury, pre treat with IV saline
102
Q

Methotrexate AE?

A
  • Teratogenecity - contraindicated in first trimester of pregnancy
  • Nephrotoxicity - deposition, treat with alkalinizing urine and IV fluids
  • Late leucoencephalopathy, meningitis - reverse with intrathecal glucarpidase, leucovorine
  • Hepatotoxicity - liver enzymes hepatitic picture
103
Q

TKI AEs?

A
  • Cardiotoxicity - prolonged QTc, cardiomyopathy, angina
  • Pleural effusion
  • Hepatotoxicity
  • Steven-Johnson syndrome