Malignant Qu 1

You SHO phones you for advice. They have been asked to review a 35 year old man who started his steroid pre-phase for ALL yesterday. The patient complained of palpitations and an ECG shows some T wave abnormalities.

-       What do you suspect and how will you proceed?

TLS

R/v fluid balance

ABG + Bloods

Cardiac monitoring + reverse K+

Contact Renal / ITU

-       What are the diagnostic criteria for TLS?

Lab: 2 or more of:

Uric acid          >476 or 25% above baseline

K+                    >6.0 or 25% above baseline

Phos                >1.45 or 25% above baseline

Calcium           <1.75 or 25% below baseline

Clinical: Lab plus one of:

Creatinine >1.5x ULN

Arrythmia

Seizures

Sudden Death

-       Can you give me any examples of risk factors for TLS?

High tumour burden

High grade tumours (ALL, BL)

Increasing Age

Pre-existing renal impairment

Cell cycle specific chemotherapy

Other drugs – alcohol, Vit C, aspirin, Caffeine, Cisplatin, Thiazides, Levodopa, Phenothiazines, theophylline

-       Can you tell me how rasburicase works?

Exogenous recombinant urate oxidase

Converts uric acid à allantoin, 10x more soluble

-       What is the dose in prophylaxis?

3mg

 

Malignant Qu 2

-       A GP refers a 57 year old man to you with a Hb 170, Hct 0.53, plt 320, WBC 6.0. How would you approach the investigation of this patient?

Repeat test with adequate hydration

Hx & Ex

O2 sats, BP, urine dip

FBC, Film, U&E, LFT

JAK2 Mutation (V617F, Exon 12)

If JAK2 neg – RCM, Epo, ABG, USS, BM Bx, Cytogenetics, PFTs, Sleep Study, VHL gene

-       The patient is positive for the JAK2 V617F mutation. Can you tell me about any diagnostic criteria for PV?

WHO vs BCSH

WHO: 3 major (Hct >0.49 / 0.48 M:F, BM Biopsy, JAK2+) or 2 major plus low Epo

-       How will you manage this patient?

4 goals:

Reduce thrombosis and haemorrhage

Reduce risk of MF / AML

Manage complications

(Manage pregnancy)

Starts aspirin 75mg OD, Venesect to Hct <0.45, control CVS risk factors

-       Would you not start cytoreduction?

No

BCSH – poor tolerance of venesection, progressive splenomegaly, thrombocytosis, constitutional symptoms

ELN – Age >60, Plt >1500, Prev thrombosis

-       Three years later patient is still venesection dependent as he did not tolerate hydroxycarbamide and he is now experiencing early satiety and LUQ discomfort. Would you give him ruxolitinib?

RESPONSE 2015 à licensed for HU resistant/intolerant PV. 222 patients, complex study.

RELIEF 2014 – no better than HU

MAJIC 2016 – results awaited

 

Coag Qu 1

-       Tell me the principle of preforming an activated partial thromboplastin time

Blood collected into citrated tube.

Centrifuged to produce PPP

PPP + Activator + Phospholipid, incubated at 37oC

Add calcium and time to clot

-       Tell me about the method or analyser your lab uses for this?

ACL Top, Silica activator, change in optical density

-       What is Quality Assurance and how does your lab ensure that is provides its service users with quality APTT results?

QA = Planned and systemic activities to provide adequate confidence that requirements for quality are met. Aims to provide a product that is Accurate, Reliable and Reproducible.

Internal: Staff proficiency, Quality management System (Q-Pulse), Audit, Education

External: EQA, voluntary accreditation (UKAS to ISO standard 15189:2007)

-       Your lab manager phones you and tells you that your most recent NEQAS submission has been returned as outwith consensus. You reported an APTT of 36 seconds, compared to the method median of other labs which reported 43 seconds. What would your initial actions be?