Bloody Minded

This week we continue the pattern of guests who are really really ridiculously good at haematology and also really really ridiculously nice people as well. We are very excited to be joined by Dr Michael Krigstein who many of you would know as the a molecular haematology guru who has gotten countless patients through their diagnoses and countless haematology trainees through their exams.Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What happens when you take someone who is really really ridiculously good at haematology and also a really really ridiculously nice person as well? You get Dr Jad Othman, consultant Haematologist and Haematopathologist at Royal North Shore Hospital in Sydney who will be joining us today to discuss the use of measurable residual disease in acute myeloid leukaemia.Dr Othman is well suited to this topic, having written his doctoral thesis on molecular disease assessment in AML, sitting on the European LeukaemiaNet (ELN)-DAVID MRD Working Group as well as numerous ALLG AML and MDS working groups. We're delighted to have him field the Bloody Minded Crew's questions today. Timestamps01:00 - The boys making outdated millenial references02:50 - Getting to know Dr Jad Othman09:50 - The concept of MRD11:55 - Lab techniques for MRD17:59 - Why doesn't everyone have an MRD marker?20:51 - What makes a good MRD assay?24:14 - Patients without a molecular MRD marker26:21 - Clinical case30:30 - What we do with MRD results31:47 - The NPM1/FLT3 PB/BM situation35:31 - Why MRD is actually helpful39:40 - Why single agent treatment in AML is challenging44:33 - The 2025 ELN DAVID update48:44 - Does doing MRD improve OS?52:21 - The INTERCEPT study55:41 - Wrap up and summarySupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Here’s a question, what do CD123, CD4 and CD56 have in common? Other than pleasing The Count on Sesame Street. Sorry, another question perhaps - what happens if you cross a plasma cell and a dendritic cell? The answers to these questions can be found on a most enigmatic myeloid cell - the plasmacytoid dendritic cell. And what happens when these rare beasts become neoplastic - why BPDCN of course. Embark on a journey into this weird and not so wonderful (but highly examinable) neoplasm with the Bloody Minded Crew TIMESTAMPS 0:57 – A glimpse into Cale's psyche 2:39 – Intro to BPDCN 6:56 – What IS a plasmacytoid dendritic cell? 10:24 – Pathological PDCs in BPDCN 11:42 – Clinical presentation – lots of rash talk 15:23 – Morphology in BPDCN 17:48 – Immunophenotype 21:16 – Karyotypic and molecular features 22:44 – Treatment of BPDCN 24:00 – A bit on prognostic markers 25:03 – Transplant 25:28 – Tagraxofusp 29:15 – Other treatment options 31:33 – Take home messages Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

“It’s pronounced nuc-ul-ophosmin” “Nucleophosmin”. “Noo-clee-o-phosmin”. FLT3-ITD got you In The Dumps? Have a Total Knowledge Deficit about TKD mutations? Struggling with the A-B-Cs of NPM1 mutations? Want to know how a cat sarcoma is somehow related to AML? Join the Bloody Minded Crew as they flit about the laboratory looking at the structure of FLT3 and NPM1, what these proteins usually do and how we test for mutations in the advanced myeloid episode.== Edit 6/5/26 = We've been made aware that strictly speaking the current MANE approved transcript for NPM1.1 has only 11 exons and therefore the mutations are best to be considered in Exon 11 as opposed to exon 12 - in contrast to what we said. ==Timestamps0:52 - Bloody Minded issues a formal apology2:40 - Introducing molecular chaperones5:05 - What even NPM1?9:30 - Functions of NPM110:55 - Molecular biology of NPM1 in disease15:42 - Why the subtypes are important19:53 - NPM1 prognosis21:35 - MRD testing in NPM125:52 - NPM1 summary27:13 - Intro to FLT328:30 - Mandatory FLT3 history36:28 - FLT3 pathogenesis37:37 - FLT3 structure, ITD vs TKD41:16 - The juxtamembrane domain42:53 - Prognostic features in FLT344:17 - TKD mutations46:26 - FLT3 in the lab50:30 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

U-G-L-Y, you ain't got no alibi, you dysplastic yeah yeah you dysplastic. Apologies to all the ring sideroblasts out there, but this week the Bloody Minded crew is doing a Mean Girls and judging cells by their morphology. For now we’re deciding to ignore those that would argue that it’s what’s on the inside that counts (i.e. judging by NGS… that’ll come later).TIMESTAMPS2:28 - For some reason, an audio podcast on visual dysplasia 5:05 - Normal erythroid morphology 7:17 - Dysplastic erythroid morphology 17:32 - Normal granulocyte morphology 20:00 - Dysplastic granulocyte morphology 28:33 - Monocyte morphology - dysplastic at baseline 30:33 - Normal megakaryocyte morphology 32:24 - Dysplastic megakaryocyte morphology 35:02 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What do arsenic, acne tablets and Jodi Picoult have in common? Why, it must be a deep dive with Nick, Bashar and Cale on acute promyelocytic leukaemia. From buzzwords to brain bleeds, the sweetest of translocations to the cruellest of coagulopathies... The yield is almost as high as the survival rates.TIMESTAMPS00:57 - Bloody Minded Poetry Jam & Jodi Picoult06:25 - APML Starts Here08:02 - APML - Where does it fit in AML?10:02 - Morphology & Flow12:12 - PML::RARA - t(15;17) and rare variants16:58 - Lab Summary17:50 - Clinical Presentation21:02 - APML Coagulopathy26:46 - Treatment and Risk Stratification33:53 - High Risk Aside36:58 - Differentiation Syndrome41:04 - Treatment SEs44:18 - Microgranular Variant47:00 - Summary and TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

After our initial intro to AML back in ep 79, we are back to dig deeper into AML this week, from pathophysiology through to treatment overview. The boys are joined by final year registrar Dr Georgina Calov who is here to cut through our nonsense and deliver some actual high yield content. And thank goodness for that, otherwise it'd be an hour of us making bad April Fool's day jokes.Timestamps2:09 - Introducing Dr Georgina Calov3:34 - AML Refresher7:12 - AML defined by recurrent genetic abnormalities15:39 - AML defined by differentiation (aka whats with the M numbers)18:14 - MN-pCT19:03 - Prognostication - ELN Classification21:58 - Diagnosing AML - Clinical24:16 - Diagnosing AML - Lab31:39 - New AML Workup35:50 - Intro to Treatment - Induction in "Fit" patients41:40 - Treatment - Consolidation & MRD45:15 - Treatment - "Unfit"48:02 - Treatment - Supportive50:16 - Treatment - Relapse/Refractory55:19 - SummarySupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Cat got your tongue? Or in this case - mucositis? Does converting the acute allogeneic transplant patient who can no longer eat's medications to IV fill you with dread? In this practical for once episode join consultant haematologist Dr Alison Chandler as well as haematology pharmacists Andriana Colic & Ariana McCauley as they take us through the how to of this challenging, but very common, clinical scenario. Timestamps0:58 - Nick's literal nightmare2:18 - Today's outline3:38 - Let's meet the A-team!11:14 - What do you wish the haem doctors knew?13:38 - Introducing the NBM transplant patient15:18 - Tacrolimus17:37 - Mycophenolate19:51 - Ciclosporine (or cyclosporine or CsA or CyA, whatevs)22:20 - Hot tip on TDM23:47 - Antifungals24:23 - Posaconazole26:06 - Voriconazole27:29 - Isavuconazole28:45 - Echinocandins - mica/anidula30:52 - Antivirals33:27 - CMV treatment37:41 - Antibacterials - PJP prophylaxis39:22 - The NBM APML patient 43:35 - Antiepileptics46:24 - TLS prophylaxis47:53 - Wrap up time!50:18 - Episode summarySupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Was episode 79 too light on MDS for you? “Amateurs” you said, adjusting your sellotaped glasses. If so, you’re in the right place today as we prepare to look at classification, risk stratification and treatment of myelodysplastic syndrome. You also should seek out psychiatric attention, or perhaps just go outside. But in the meantime, enjoy this episode where we’ll dig deeper into the nitty gritty of MDS! We’ve got a lot to cover so we float about between intermediate and advanced for this episode.TIMESTAMPS1:11 - A Very Unhinged Intro  3:34 - Actual Content Starts Here  5:52 - Differentials for dysplasia  7:54 - Presentations of MDS  12:36 - MDS Subtypes  14:23 - MDS with del(5q)  18:29 - Lenalidomide in del(5q)  25:03 - MDS with SF3B1  29:05 - MDS with biallelic TP53 inactivation  30:26 - Bonus cytogenetic abnormalities that pop up  31:43 - Germline mutations that predispose to MDS and AML  37:14 - MDS with low blasts  38:08 - Ogata Score  39:26 - Hypoplastic MDS  44:03 - MDS with increased blasts  44:58 - MDS with increased blasts and fibrosis  46:22 - Breaking News - Blasts Should Now Be Counted By Flow  48:30 - Prognostic models for MDS  53:36 - Treatments for MDS  1:04:39 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What if the prequel had a prequel? Join Bashar, Nick and Cale as they attempt to unpack the newfangled world of clonal haematopoeisis. Find out how CHIPs can kill and no, it’s not due to eating too many of them too fast. Though that might do it too. We’ve had one spectrum, but what about a second. We need to go deeper. TIMESTAMPS0:56 - A classic chippy mixup  2:56 - Episode overview  3:54 - Where CHIP sits in haem  5:15 - Clonal haematopoiesis  11:21 - What genes acquire CH?  13:42 - CHIP  20:09 - Clinical implications of CHIP  24:24 - Increased mortality in CHIP  28:54 - ICUS  32:40 - CCUS  35:42 - Take home messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

 If we’re going to truly understand myeloid disease, we must dispense with the ward and journey to the dystopian heart that beats at the centre of each dysplastic cell. Learn what is valid and in-valid as we swim across an ocean of concepts - past the basic principles of DNA and RNA, Polymerase Chain Reaction and its many many variants, Fragment Analysis and Next Generation Sequencing. Just save a little something for the swim back to clinic next week.PS The Extra T is for TYOTT Timestamps0:55 - Back in the lab, baby!2:08 - Today's outline6:24 - What IS molecular testing?8:13 - The central dogma of molecular biology14:46 - Types of genetic mutations20:05 - Nomenclature for gene variants (advanced)23:52 - Samples for testing27:42 - What comes after DNA extraction30:11 - What is PCR and how did we discover it? 38:45 - What we do post PCR41:27 - Quantitative and RT-PCR 46:54 - Asking the RIGHT question48:55 - Digital droplet PCR50:44 - Electrophoresis52:35 - Fragment analysis and melt curve analysis54:33 - NGS1:00:02 - What is a VAF?1:05:23 - Lab governance (for haem ATs)1:09:32 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Happy marrows are all alike; every unhappy marrow is unhappy in its own way.  When haematopoiesis behaves itself, it’s frankly quite boring. When it goes rogue, it can get very creative. Join Cale, Bash and Nick as they attempt to walk through how this process goes off the rails, how MDS and AML are best understood and how dysplasia, cytopenias, blasts and clones all fit together.TIMESTAMPS0:55 - Our serious introduction to counterbalance last week 1:58 - Episode overview 2:50 - Introducing MDS 7:12 - Risk factors for MDS 8:53 - MDS progression 11:13 - Complications of MDS 13:10 - Leukaemic transformation 15:37 - MDS epidemiology 16:27 - Diagnosing MDS 21:19 - What is dysplasia? 26:44 - What we test on marrow 35:13 - Clonality assessment in MDS 42:29 - Caveats in diagnosing MDS 43:18 - MDS summary (finally) 44:09 - MDS treatment in brief 45:37 - Intro to AML 51:32 - Episode summary Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What’s a CHIP and why is it so delicious? Why do we still abbreviate myeodysplastic neoplasm to MDS? How did Bashar get his hands on the Necronomicon? These are questions that every budding haematologist asks themselves at some point and we will answer at least some of them here! Join us today for a birds-eye overview of the myeloid family of disorders before we dig into them more over the coming weeks. TIMESTAMPS0:57 - Does anyone know a good priest?  3:17 - Myeloid conditions in bucket form  5:30 - Acute vs chronic in haematological diseases  7:35 - Myeloid precursor lesions  10:33 - Myeloproliferative neoplasms  15:23 - Myelodysplastic syndromes  18:50 - MDS/MPN Overlap Syndromes  22:29 - Mastocytosis  26:02 - Acute myeloid leukaemia  28:23 - (Acute promyelocytic leukaemia)  29:36 - Histiocytic/dendritic cell disorders  31:14 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Hi-ho, Hi-ho, it's off the myeloid factory we go. Grab your fastest belt, a spare inserter and all the iron plates you can get your hands on as the Bloody Minded Crew embark on their nerdiest references yet and learn all about the basic science behind myelopoiesis. You’d better hop on a train, because the only main bus here goes straight from the marrow out to the periphery carrying all sorts of myeloid cells. And some blue circuits. 0:52 - New year same us2:44 - Season overview: myeloid time, baby!5:15 - What is the myeloid compartment?7:29 - Myelopoiesis12:49 - Stem cell destiny... does free will exist?14:28 - The myeloid progenitor16:30 - Red cells and platelets17:46 - White cell maturation19:34 - Hormonal control of myelopoiesis21:25 - Historical diversion into GCSF23:19 - Clinical use of stimulating factors26:39 - GCSF Bone Pain28:15 - Emergency Myelopoiesis30:08 - Wrap UpSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

So you’ve been asked to start a DOAC? How is that different from a NOAC? Is there a difference? Which one should you start? Is warfarin a WOAC? How do I initiate these drugs? Why is the dose weird at the beginning? Do I need to check my dose is appropriate? If oral anticoagulation has you discombobulated you are in the right place!! In part II on the practical management of anticoagulation we are here to clarify all your questions on the most common types of oral anticoagulation you will come across as a junior doctor on the wards.Timestamps1:44 - Part I Recap and Part II Introduction3:44 - History of Warfarin8:37 - Mechanism of Warfarin13:01 - Monitoring Warfarin16:52 - Why Warfarin? and warfarin tips21:40 - Warfarin reversal31:05 - Warfarin Skin Necrosis & Drug Interactions36:08 - Warfarin in Special Circumstances40:25 - DOACs Intro41:12 - Dabigatran48:25 - Anti-Xa Agents (Rivaroxaban / Apixaban)52:38 - Anti-Xa Monitoring (or not)59:28 - DOACS - Special Circumstances1:05:58 - WrapupSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Does my blood look fat in this?Does the idea of heparin being a fraction make you wish you listened harder in maths? What is unfractionated heparin? Why are haematologists so judgmental and prefer their anticoagulation low molecular weight? Why does haematology frown when you use the term “blood thinners” ?!?!If injectable or parenteral anticoagulation feels confusing you have come to the right place! Today we look at unfractionated heparin and low molecular weight heparin,  practical things to think about and how to manage these drugs safely on the wards and beyond NB We’re going to leave the advanced injectables like Fonda/Danaparoid/Bivalirudin to a dedicated alternative, probably HITTS themed episode if you’re looking for these drugsSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Twas the night before Christmas, and all through the house, not a creature was stirring, particularly not a missing coagulation factor. Welcome to a very special present all wrapped and delivered by Santa and his Christmas elves and stuffed in your podcast queue in time to drive off for the holidays. Join Cale, a very dusty Bashar, Nick and Santa as we learn a little bit about Christmas Disease. We swear his jacket was that colour before we messed with his haemostatic pathways… CONTENT WARNING: SingingTIMESTAMPS00:55 - Pure unbridled musical talent 03:34 - Intro to Christmas Disease/Haemophilia B04:58 - History of Haemophilia B14:01 - Presentation of Haemophilia B18:25 - Haemophilia B Leyden22:49 - Coagulation studies in Haemophilia B26:20 - Treating Haemophilia B28:12 - Where does factor replacement come from?31:57 - Inhibitors33:48 - Gene therapy37:27 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

We’ve had one difficult coagulation topic yes, but what about second difficult coagulation topic? We are joined by the fantastic Dr Caroline Dix today to take us through not one but TWO challenging scenarios in thrombosis. First we’ll be revisiting Cerebral Venous Sinus Thrombosis but this time with someone who knows what they are doing. After that we’ll cover anticoagulating people when some very fundamental parts of the system are broken - the management of antithrombin deficiency. This episode wraps up our journey through clots… for now. Timestamps:2:08 - Introducing Dr Caroline Dix8:03 - CVST - Risks11:15 - CVST - Clinical18:08 - CVST - Duration21:05 - Antithrombin Deficiency25:12 - Antithrombin Deficiency - Diagnosis29:43 - Antithrombin Deficiency - Management37:34 - WrapupSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Sometimes something comes along that puts a chill down the spine of every doctor. Any conversation that starts with "Oh hey do you remember that patient you saw...?". Mystery meat day in the cafeteria. Dealing with hospital executives. For these times in life you need a guide. Today we'll be covering one of those spine-chilling clinical scenarios with our very apt guide consultant haematologist Dr Sara Ng. Over forty minutes Sara will un-chill your spine with her practical approach to managing thrombosis when there just aren't that many platelets to go around, as well as talking about conditions where clots and thrombocytopenia are intimately linked.Timestamps: 2:11 - Introducing Dr Sara Ng7:18 - Case 1: Acute PE and Thrombocytopenia14:55 - Case 1.5: Subacute PE and Thrombocytopenia18:20 - Case 2: Line Thrombus during Chemotherapy22:09 - Thrombosis in ITP26:15 - Oh no a STEMI27:44 - Two sides of the same coin31:58 - How 2 4T Score - HITS35:15 - Other PF4 Antibodies38:33 - Wrap up & TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Come one come all to see the thinnest extended reference in the universe. Draped over not one but TWO episodes, the Bloody Minded Crew continue to make vaguely topical references to popular recent films. Look - we go outside and experience the full gamut of popular culture. Oh and we finish up our discussion of thrombophilia testing in the lab - looking this week at activated protein C resistance testing, molecular Factor V Leiden assessment and Prothrombin gene mutations.TIMESTAMPS1:06 - Pay no attention to the man behind the curtain3:10 - Activated Protein C resistance testing10:27 - Testing in Australia for APCR17:17 - FvL Testing18:51 - PCR - Polymerase Chain Reactions22:52 - Melt curve analysis27:39 - Prothrombin G20210A Testing28:44 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Lions and tigers and… thrombosis? Oh my! Join the Bloody Minded Crew on the yellow brick road to visit the emerald laboratory and see the wonderful wizard of clots - your friendly laboratory coagulation scientist! Put on your blood red ruby slippers and join us for this bumper lab episode as we learn about how exactly we test for Protein C, S and antithrombin deficiencies as well as lupus anticoagulants. By the end of it you’ll have a brain for coags, a heart full of of love for thrombosis and the courage to peer behind the laboratory curtain Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

“HATE. LET ME TELL YOU HOW MUCH I'VE COME TO HATE YOU SINCE I BEGAN AS A HAEM REG. IF THE WORD HATE WAS ENGRAVED ON EACH NANO-ANGSTROM OF THE HUNDREDS OF MILLIONS OF CONSULT NOTES I HAVE WRITTEN IT WOULD NOT EQUAL ONE BILLIONTH OF THE HATE I FEEL FOR YOU ORDERING THROMBOPHILIA TESTING INAPPROPRIATELY.” Woah - Let’s calm down, that's a bit much. Cale and Bashar are exposed to Nick’s inner monologue as the Bloody Minded Crew learn about the what, when and when not of thrombophilia testing. TIMESTAMPS0:52 - Nick gets stuck in an anger loop  2:19 - Intro to thrombophilia testing  4:25 - Inherited thrombophilias  5:38 - Surprise historical diversion on antithrombin  8:14 - Proteins C and S  9:31 - Factor V Leiden  10:56 - Prothrombin gene mutation  11:52 - Risk profiles in inherited thrombophilia  18:49 - Acquired thrombophilias  18:56 - Antiphospholipid syndrome  19:46 - PNH  20:22 - JAK2  21:08 - Mid-ep summary  22:28 - The world's biggest soapbox: what not to do  23:25 - Soapbox: no MTHFR pls  25:19 - Soapbox: bad times to test  26:46 - Soapbox: don't test the obvious provoked clots  27:30 - Bonus soapbox: factor V levels vs Leiden  28:54 - When SHOULD we test?  30:41 - Benefits of testing  32:33 - Clinical scenario: spoiler, no real answer  33:26 - Scenarios where you might test  37:49 - Take home messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

We're nearly out of pipes to clean - Join us for the world's worst roadtrip we venture into the lesser known parts of human plumbing and tackle unusual site thromboembolism. From splanchnic clots, uterine and testicular thrombi it's clots as far as the eye can see (and those it can't like CRVO!)Timestamps:0:58 - ROADTRIP4:07 - CVST11:07 - CVST - Treatment15:36 - Lemierre's17:50 - CRVO24:36 - Splanchnic Thrombi34:45 - Renal Vein Thrombi39:41 - Uterine Vein Thrombus42:09 - Ovarian Vein44:42 - Testicular Vein46:35 - TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

It's said that beauty is skin deep but you know what else lurks just under your epithelium - CLOTS! Nick, Cale and Bashar head very slightly under our outer layer to the peripheral vasculature in this increasing tortured metaphor as we learn on our shortest episode to date about what to do when those not so deep vessels fill with thrombus. Timestamps2:12 - Where are superficial veins?5:23 - What's the deal with thrombophlebitis7:34 - MONDOOORS (To the tune of Trogdor)9:11 - Risk Factors for SVT10:56 - Investigations11:53 - Treatment17:54 - SummariesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

D-ismayed by D-readful D-ressing D-owns by your D-emonstrably D-eplorable registrar? . Join de Bloody Minded Crew for a Tour D-Force of D-Dimer D-rama as we D-issect and D-iscuss this most D-ifficult of D-iagnostic tests!Timestamps2:14 - What is a D-Dimer and where does it come from?6:57 - FXIII and D-Dimer7:49 - Fibrinolysis and other degradation products10:18 - D-Dimer Assays - LIA14:22 - D-Dimer Units - Important!15:39 - D-Dimer Assays - ELISA / ELFA16:59 - D-Dimer Assays - POCT18:13 Comparing Assays & Analytical Factors22:12 - D-Dimer Interpretation - Clinical listeners start here!30:16 - D-Dimer and Cancer32:31 - D-Dimer and DIC34:32 - Summary and TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

“Give me a 2cc bolus of clot stat Emma. No wait - not there!” But it was too late, and Em-Bolused the 2cc of clot straight to the lungs”. Join the Bloody Minded Crew as they get to the heart… no get to the lungs of the topic of Pulmonary Embolism. VanQuish the V/Q and CriTically aPprAise the CTPA with these acronyms that are just as bad as a cardiology trial and half as useful. Sadly the Top Gun soundtrack is copyrighted but nothing will stop you playing Berlin over the background of the intro (and we’d strongly suggest it). Timestamps4:55 - Types of PEs7:14 - Risk Factors for PE8:55 - Signs & Symptoms ft. ECGs12:15 - Investigations21:49 - Vibe Augmenting - Decision Scores25:59 - Brief Recap26:44 - Treatment39:15 - Pregnancy44:35 - Take HomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Calves, thighs, arms and more, Clots can form inside them all!Join your hosts Cale, Bashar and Nick as they take a deep (hah) dive into the nitty-gritty things you should know about managing DVTs of the extremitiesTIMESTAMPS0:54 - Intro to Extremity Clots3:49 - Veins of the Lower Limb5:54 - History & Exam Lower Limb10:54 - Phlegmasias15:52 - Investigations21:27 - Below Knee DVTs26:41 - Proximal Lower Limb29:40 - May-Thurner33:04 - PTS34:33 - Upper Limb41:15 - How long to anticoagulate?45:28 - Take HomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Rudolf the red nosed physicianWrote a very cool triadAnd if you ever saw ityou would even say ‘Egad!’All of the other physiciansused to laugh and call him dumbThey never let poor Rudolf join in the MDT funThen one foggy clinic daya patient came to say “Rudolf with your triad so smartwon’t you describe to me the pathophysiology of clotting in a way that both makes sense and fits inside the metre of this children's song”But he couldn’t, so welcome back to our next batch of episodes on the pod as we tackle the wonderful world of venous thromboembolism. How do I ask a patient about clots? Is a provoked thromboembolism when you call it names? Join Nick, Cale and Bashar jumping into the wild world of clots...TIMESTAMPS0:58 - Episode Intro2:51 - Crafting a Clot Redux - Haemostasis7:21 - Turbo Coag Cascade8:34 - Thrombosis History12:17 - Why we bother with history16:39 - Risk factors for VTE21:41 - Major vs Minor risk factors23:54 - Thinking about risk factors26:04 - The Thrombosis History32:53 - Management Overview37:40 - Summary and TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Philip K. Dick once wrote, “Perhaps if you know you are insane then you are not insane. Or you are becoming sane, finally. Waking up.” Waking up, that is, not to the alternative history universe where the Axis won WWII but rather, to a new bonus episode on Castleman disease! Join Cale, Bashar and Nick as we explore one of Haem’s most zebra diagnoses, and do whatever we can to put off Nick’s clot season for just a bit longer.TIMESTAMPS:00:53 - Holiday to Bavaria04:12 - Basics of Castleman Disease07:41 - Histological Subtypes10:57 - Clinical Subtypes - Unicentric13:05 - Clinical Subtypes - Multicentric16:08 - Brief Recap18:00 - Pathophysiology of Castleman21:38 - Historical Diversions23:54 - Investigations25:30 - Treatment - UCD26:44 - Treatment - MCD31:02 - Rarer than a Zebra (POEMS/TAFRO)37:23 - Summary and TakehomesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Have you stumbled onto the haematology ward only to discover patients on bizarrely named BiTE & CART therapy? Why are we giving patients CARTs? Do they come with a horse?  Why does everyone freak out when these patients are febrile? Why is everyone so hung up about handwriting? What are these weird drugs? It's OK – we are here once more to demystify the acronyms – and help you know what we are giving, why we are giving it and how to manage complications of Bi-Specific and CAR-T therapy! TIMESTAMPS3:48 - Intro to BiTEs  5:26 - Intro to CAR-T  8:27 - Examples of BiTEs  16:36 - CAR-T Collection + Production  18:44 - Examples of CAR-T Products  19:35 - Similarities and Differences between BiTEs and CAR-T  23:24 - Cytokine Release Syndrome (CRS)  30:23 - Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)  39:29 - Treatments for CRS  45:52 - Treatments for ICANS  50:01 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Bamboozled by basophils bountiful booty of granules? Let’s begin brilliantly with a basophil based bonanza. Buckets and buckets of brazenly basophil related bonus banter. You beauty! But, beware the bawdy, boisterous boys babbling brobdignagian-ly about BASOPHILS. It sounds better if you read it in Hugo Weaving’s voice and it’s the 5th of November I swear. TIMESTAMPS3:07 - What are basophils?  6:54 - Snapping turtle trivia  7:55 - Role of basophils  9:42 - Basopenia  10:41 - Cutoffs (arbitrary as usual)  11:14 - Artefactual basophilia  12:29 - Reactive basophilia  14:27 - Haem Causes = MPNs Galore  16:14 - CML (Again)  19:17 - Zebras have hoofbeats too  23:20 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

The mighty eosinophil had triumphed. The last parasitic worm lay vanquished beneath his granule-studded pseudopodia. For years, he’d battled helminthic scourge, a hero in mucus armor. But now, with no foes left to smite, he grew restless. He turned his sharp gaze to pollen, peanuts, and pet dander. "Troublemakers," he muttered, unsheathing his cytotoxic arsenal. With righteous zeal, he charged into the sinuses and skin, sparking sneezes and wheals in his wake. “A threat is a threat,” he declared, as a baffled immunoregulatory system looked on. The worms were gone - but the war had only just begun. With more excerpts leaking from the Bloody Minded Cinematic Universe, it’s only a matter of time until our movie deal.TIMESTAMPS2:48 - What are eosinophils?  4:44 - Cutoffs (arbitrary as usual)  7:12 - The Problem with Eosinophilia  8:32 - Infective causes  9:32 - Medications  10:36 - Other Secondary Causes  12:32 - Haem Causes - CML and More  18:08 - Quick Recap  19:49 - Approach to eosinophilia  24:31 - Treatment options  25:52 - Case Study - Not Geraldine, I Promise  28:52 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Put on your monocles and kimonos and hop on the monorail to our episode composed of monotonous monologues, monogamously dedicated to that most monolithic and sometimes monoclonal of mononucleated cells. We are monobviously talking about the monocyte. TIMESTAMPS0:57 - Mono-Cyte!  2:50 - What is a monocyte?  4:20 - Monocyte subclasses  6:00 - Role of monocytes  8:10 - Causes of Monocytopenia  9:43 - Hairy cell leukaemia  12:42 - Reactive monocytosis  15:10 - CMML - Not a Typo  22:20 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Behold the field in which I grow my cells and see that it is barren. It’s out of the frying pan and into the aplastic fire with not a cell in sight. Join Nick, Cale and Bashar without two neutrophils to rub together as we talk about an approach to that most concerning of FBC features - pancytopenia. TIMESTAMPS2:22 - Definition of pancytopenia  4:23 - Spurious pancytopenia  6:04 - Cutoffs (arbitrary as usual)  9:43 - Acquired aplastic anaemia  15:30 - Inherited bone marrow failure syndromes  18:52 - Environmental toxins  19:47 - Medications  20:52 - Haematinic deficiencies  25:59 - MDS/Leukaemias  30:54 - Marrow suppression  33:32 - Infiltrative causes  36:45 - Viral causes  38:05 - Approach to pancytopenia  39:06 - History  40:12 - Examination  41:13 - Investigations  42:27 - Liver failure  44:30 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Once again the Bloody Minded Crew have ventured out of the lab to find and trap another haematology registrar from the wards and convince them to come back to the show and talk about cells. Join haematology registrar Dr Lise Kempler as she teaches the team about what to do when that lymphocyte number just creeps up and up and up. TIMESTAMPS2:34 - Aspiring to be a lymphocyte  5:44 - What are lymphocytes?  9:52 - Cutoffs (arbitrary as usual)  13:09 - Infective causes  15:21 - Morphological clues  17:23 - Investigations for infectious causes  17:54 - Flow cytometry  22:33 - Clues for Badness  23:34 - Case Studies  36:18 - T-LPDs  38:10 - ALL Out of Nowhere  40:54 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Whilst most of haematology is spent looking forlornly into the empty neutrophil cupboard like old Mother Hubbard post chemotherapy, the pendulum can also swing to the other extreme. Join us as we unpack the reactive and not-so-reactive causes of a neutrophilia so you don’t get too left-shifted on the wards.TIMESTAMPS2:18 - Apologies to the Welsh  3:07 - Cutoffs (arbitrary as usual)  4:46 - Left-shift  7:02 - Spurious neutrophilia  7:44 - Reactive neutrophilia  9:09 - Steroids  13:33 - Leukemoid reaction  15:48 - Smoking  18:49 - Clues to MPNs  20:01 - Chronic myeloid leukaemia  23:11 - Other MPNs  24:06 - Chronic neutrophilic leukaemia  26:08 - MDS/MPN Overlaps  28:57 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

A lone neutrophil stands alone against a horde of gram negative bacteria. He is the last of his kind, the single granulocyte rising from the ashes of a marrow once verdant with haematopoiesis, now overrun with blasts. As the endotoxin rushes towards him, he smiles, for on the horizon he can see the glimmer of tazocin rushing through the blood vessels like Gandalf leading the Rohirrim to Helm’s Deep. While the Bloody Minded Cinematic Universe remains in pre-production, you can sate your appetite with a podcast on neutropenia for now.TIMESTAMPS2:21 - Cutoffs (arbitrary as usual)  3:10 - An Overview of Granulopoiesis  5:24 - When is neutropenia urgent?  6:46 - History  7:32 - Examination  10:45 - Artefactual neutropenia  12:40 - Nutritional causes  13:43 - Infective causes  14:42 - Medications  16:22 - Marrow pathology  19:27 - Autoimmune causes  22:26 - Splenomegaly  22:52 - DANC  25:33 - Investigations  28:26 - Management  32:43 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

There’s a problem with billionaires at the moment. Every day, you make a hundred billion platelets. For some in our society, even that colossal quantity isn’t nearly enough. They strive ever onward for even more. Unfettered platelet production all the time forever - after all the number can only go up. But mo’ platelets leads to mo’ problems. Go on a journey with Bashar, Nick and Cale to learn how some patients can become the Bezos of platelets and accumulate more than you can possibly need or want. Don’t let us stop you having a tacky wedding though. TIMESTAMPS2:24 - Cutoffs (arbitrary as usual)  4:24 - Platelet biology  6:11 - TPO  7:53 - Spurious thrombocytosis  10:50 - Reactive thrombocytosis  12:30 - Blood loss and thrombocytosis  13:12 - TPO Kinetics  16:00 - Iron deficiency and thrombocytosis  19:10 - Hyposplenism  20:03 - Drugs  21:54 - MPNs  23:53 - Molecular Testing  25:27 - Clots AND Bleeds?!  26:58 - A General Approach  29:17 - Can we test TPO?  30:29 - Case Study  31:44 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Are you a platelet that has been conjugated to an antibody? Sequestered in a spleen? Diluted out by too much saline? Had your precious gold stolen from you? Then you might be entitled to thrombensation! Listen to this episode to learn how we can help YOU approach thrombocytopenia.TIMESTAMPS 2:23 - Striking gold where you least expect it 4:40 - Definition of thrombocytopaenia 8:06 - What do platelets do? 9:22 - History for thrombocytopaenia 12:20 - Exam for thrombocytopaenia 18:03 - Artefactual thrombocytopaenia 21:28 - Decreased platelet production 24:46 - Increased platelet consumption 24:55 - ITP 27:43 - APLS 28:15 - HIT 29:45 - Thrombotic microangiopathies 32:09 - Redistribution/Sequestration 33:41 - Dilutional causes 34:35 - Pregnancy-Related Causes 39:23 - Investigations 42:05 - Platelet Transfusion Thresholds 44:36 - Take Home Messages Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Our half empty cup from last week has now runneth over! If having low red cells is a bad thing, then having an extremely high amount must be a good thing, right? WRONG! Join the Bloody Minded Crew  as we explore what happens when we’re on the other side of that Goldilocks zone of red cells. Remember that episode of the Simpsons where they try and force a million germs through a tiny door? It’s like that but in your capillaries.TIMESTAMPS2:14 - Official First Aid Advice  2:30 - Absolute vs. relative erythrocytosis  4:49 - What's the PCV? What's the haematocrit?  7:30 - Signs and Symptoms  10:49 - History for erythrocytosis  14:02 - Causes of Secondary Erythrocytosis  21:30 - SGLT2 Inhibitors - Another Reason to Stop Them  25:36 - Causes of Primary Erythrocytosis  27:20 - Polycythaemia Rubra Vera  29:06 - Budd-Chiari Syndrome  32:20 - Elevated Hb. What Next?  33:48 - Labs - JAK2 + EPO  36:10 - Case Studies - Not Pre-Ordained At All  43:16 - Take Home Messages  Support the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

All that blood study making you faint, fatigued and short of breath? Well, you might be anaemic but how can we tell why? Join us on our first expedition of this season of highs and lows as we take apart the full blood count one episode at a time. Let’s start with an approach to a cup half-empty of blood - anaemia! TIMESTAMPS2:10 - The Motto of Haematology  3:08 - Definitions - How low is low?  4:24 - MCV is Key  6:43 - TICS and RACH have BLOOD in common  8:47 - TICS(L) - Microcytic Causes  9:27 - Thalassaemia  12:58 - Iron deficiency  19:33 - Chronic disease  22:39 - Sideroblastic anaemia  25:35 - Lead poisoning aka med school fodder  27:46 - RACH - Normocytic Causes  28:01 - Renal Disease  30:32 - Acute blood loss  31:55 - Chronic disease back again  32:18 - Haemolysis - Pls See Season 2  34:46 - (Surprise Myeloma - Pls Also See Season 3)  35:18 - BLOOD - Macrocytic Causes  35:37 - (Except it could be retics)  36:33 - B12 Deficiency  38:43 - Liver Disease  39:16 - etOh  39:54 - fOlate Deficiency  42:04 - Drugs/Dysplasia  43:19 - The red cell maturation pathway  45:28 - Megaloblastic vs. non-megaloblastic  51:09 - Thyroid - might be a thing?  53:03 - What's in an anaemia work-up?  57:05 - Take Home MessagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Learning to count is hard. Learning to count cells is harder. Luckily we've got an expert with us today to show us the basics. Welcome back to a new batch of episodes where we unpack the highs and lows of haematology and teach you what to do with those pesky out of range blood counts. But to do that we need to know where the numbers come from. We don't know, so we asked Mitchell Rawlings a senior scientist in haematology to come along and relieve of us of our ignorance. Mitch takes us through automated analysers, the principles of cell counting, and some of those mysterious other acronyms on the full blood count. TIMESTAMPS1:25 - A year in review3:09 - Haematology Made Simple4:04 - Everyone deals with FBCs...4:52 - Mitch Rawlings5:48 - God that intro segment was long9:47 - FBC Stats10:19 - Three Letter Acronym Time13:57 - FBC Journey from Vein to Screen15:30 - Analyser Magic16:40 - Coulter principle17:56 - Ghosts in the machine19:40 - The Differential21:25 - Red Flags24:43 - Haemoglobin measurement - productive destruction26:46 - The lab doesn't hate you - please send enough blood28:53 - Retics all day long30:07 - Derived, measured, calculated parameters32:15 - QC + Drift Controls34:06 - Wrong blood in tube36:29 - Platelet counting - citrated, manual counts40:14 - Mixing "studies" - really bad for FBC42:08 - The problem with aspirating clotsSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Have you been asked to call for a Haematology consult and are now considering hiding in a toilet? Never fear! You can listen to this podcast from the hospital bathroom AND learn some fantastic tips and tricks to help us help you! Dr Alison Chandler is back in the studio and we're aiming for future consults with at least 50% less crying – and that’s not just for the Haem AT carrying the consult phone! Timestamps:00:54 - Nick is MIA03:06 - Picking up that phone06:44 - Consult 1) New Thombosis19:50 - Consult 1.1) Superficial Thrombophlebitis22:40 - Consult 2) Deranged Coags31:35 - Consult 3) Cytopenias49:27 - Bonus Consult: Thrombocytosis52:14 - SummariesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Bashar was tasked with finding an expert to talk to about blood banking. He decided to cold-email the best transfusion-educator in the world who is probably responsible for hundreds if not thousands of haematology trainees understanding blood banking. Turns out he's an absolutely lovely guy who decided to spend an hour of his Monday morning chatting to us about podcasting, education, IgA deficiency and all the wonderful aspects of the blood bank. Join us for an hour with Dr Joe Chaffin MD, much more widely known as "The Blood Bank Guy".For more of Dr Chaffin's excellent work, check out www.bbguy.org & The Blood Bank Guy Essentials Podcast wherever you get your podcastsTimestamps1:00 - Containing our excitement3:38 - The Joe Chaffin story8:15 - Getting into education17:40 - Surprising moments in podcasting22:45 - How to improve transfusion teaching27:50 - The Blood Bank/Clinician interface38:31 - What scares the Blood Bank Guy?46:42 - The future of blood banking49:53 - What to unlearn57:19 - TA-GVH made easy1:01:24 - Final words of wisdomSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Red cells. White cells. Platelets. Plasma. Proteins. By your powers combined I am Captain… Whole Blood? Wouldn’t it be so much easier if we could work with each of these blood components individually. After all, we have to get them in a bag to donate to people. Before we swear off transfusion for the time being, join the Bloody Minded Crew as we learn the get back to basics of the apheresis machine, the concept of plasma exchange and how the magic of technology allows us to manipulate these components separately. Why keep all of your humours mixed together if you don’t have to? Hippocrates could never.Timestamps0:55 - Our stupidest and best intro to date3:10 - What is apheresis?8:05 - Indications for apheresis13:21 - Mechanism of apheresis17:52 - Replacement fluids19:23 - Physiology in plasma exchange22:13 - Complications of plasma exchange30:50 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Join our visiting expert Dr Eoghan Molloy - Multitalented transfusion medicine specialist and consultant haematologist at Cork University Hospital to teach us how to cross the ABO Rubicon and provide transfusion support in ABO mismatched transplantation. Visit the lab and see what happens to the forward and reverse group when you're in the middle of changing groups. Brush up on your major, minor and bidirectional mismatches as the generally mismatched Bloody Minded Crew learn from a real expert again. PS Nick had his microphone set to ASMR so there are a few hiccups in the audio quality but the content was too good to missTimestamps:0:59 - Nick's real overseas friend2:52 - Intro to Dr Eoghan Molloy9:10 - ABO incompatibilities in transplant15:19 - Graft manipulation17:47 - Patient preparation in ABO mismatch20:44 - Provision of blood products in transplant32:51 - Red cell aplasia in transplant38:16 - Passenger lymphocyte syndrome40:37 - CMV in transplant46:06 - Irradiated products52:12 - Clinical case and wrap upSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

FOUR Antibodies. THREE Animals. TWO Crying Haem Registrars. ONE TEST - The MAIPA. Actually maybe more than two crying haem registrars. How many antibodies are too many antibodies to have inside a lab test? One? That’s just a DAT. Two? A mere sandwich ELISA. But the Monoclonal Antibody Immobilisation of Platelet Antigens (MAIPA) - that’s not just three but FOUR separate antibodies in the same test. If somehow you’ve made it this far thinking there wasn’t enough immunohaematology for you then it’s time to join the Bloody Minded Crew as they wrestle with the most anti-bodied of tests. Oh and we look at other platelet antibody testing too.Timestamps00:52 - Thanksgiving in the lab03:42 - Platelet antigens refresher06:10 - FNAIT10:55 - Transfusing in FNAIT20:18 - Testing for FNAIT26:56 - The PIFT29:39 - The MAIPA37:20 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Have you ever looked at your wallet after a big night out and seen that all your dollars have been conjugated to alloantibodies and phagocytosed by macrophages? Then you know what it’s like to transfuse a platelet refractory patient! Join us as we take a tour of platelet refractoriness and do our best to find some HLA-matched dollars for rent this week.Timestamps00:52 - Bashar lives near a nuclear reactor2:03 - Clinical case5:38 - Defining platelet refractoriness7:46 - Calculating platelet increments12:42 - Causes of refractoriness18:10 - Immune mechanisms of refractoriness21:23 - HLA in detail25:03 - HPA antigens27:39 - Testing31:46 - The Luminex assay34:00 - Managing immune refractoriness43:26 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Has this season been too simple? Want to up the difficulty? First of all you have issues, but second of all, welcome! It’s time to talk about all the things we don’t tell people about in the wider hospital - rare blood groups, subgroups, laboratory tips, tricks and more on this bumper In The Lab episode. Timestamps:0:52 - How to get rich quick3:58 - Episode overview4:50 - The other blood groups9:07 - Kell11:37 - Duffy13:54 - Kidd16:53 - MNS18:46 - ABO subgroups22:28 - D variants28:29 - Enzymes in pretransfusion testing33:35 - Elutions37:46 - Adsorptions44:05 - ABO discrepancies47:01 - Take home messagesSupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What’s scarier than picking blood for one patient? Picking blood for TWO patients where one of them is inside the other (or only very recently outside). Obstetrics isn’t immune to the acronym train so join Nick, Cale and Bashar as we talk about HDFN, RhD prophylaxis and that OMG sensation that comes when looking after some of our smallest patients. Timestamps:0:58 - Trust me this is worth it2:30 - Episode overview4:22 - Transfusion in pregnancy5:52 - Kell in pregnancy6:47 - Transfusion in neonates9:58 - Intrauterine transfusion11:00 - HDFN: Haemolytic Disease of the Fetus and Newborn13:17 - Anti-D antibodies in HDFN17:35 - Estimating FMH20:23 - Anti-D prophylaxis24:52 - Managing maternal alloantibodies26:38 - Other important antibodies31:20 - NIPT33:00 - Episode SummarySupport the showCheck out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au