In this episode, we review the high-yield topic of Microangiopathic Anemia from the Hematology section.

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In this episode, we review the high-yield topic of Heparin-Induced Thrombocytopenia (HIT) from the Heme section.

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In this episode, we review the high-yield topic of Immune Thrombocytopenia (ITP) from the Hematology section.

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We revisit a topic covered previously as part of our “Heme/Onc Emergencies” series: heparin-induced thrombocytopenia (HIT) in Episode 017. As part of our return, we dive deeper into the pathophysiology, principles of diagnosis, and management of HIT to help you to better understand how to approach the question of “is this HIT?” as a Hematology consultant and, more importantly, how to guide management based on your index of suspicion.

Content:

- What is the pathogenesis of HIT?

- What are risk factors for HIT?

- How do we diagnose HIT?

- What are the assays that we use to make this diagnosis and how do the assays work?

- Practical points about management of HIT/HITT

** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodes

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This week in our hematological consultation series, we continue our discussion on von Willebrand disease (vWD), this time focusing on the type 2 subtypes and we also discuss management.

In case you missed it, we recommend checking out episode 069 for Part I of this vWD series, covering taking a bleeding history and about Type 1 and Type 3 disease.

Content:

- What testing do we send for suspected vWD (refresher)

- What to do if type 2 vWD is suspected?

- What are the different subtypes of Type 2 vWD?

- What is "platelet-type vWD"?

- What is the approach to perioperative management?

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We resume our hematological consultation series with an overview of von Willebrand disease, the most common inherited bleeding disorder. In this episode, we talk about the initial steps we should take to evaluate suspected von Willebrand disease (vWD) and how to differentiate the various subtypes. We will focus on vWD type 1 and 3! Be sure to tune in next week as we discuss vWD type 2 and management.

Content:

- Taking a bleeding history

- What is von Willebrand factor?

- What tests should we order for diagnosis?

- What are the different types of vWD?

- What is the DDAVP challenge?

** Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodes

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We are taking a small pause from our breast cancer series to discuss an important topic that is so critical to understand for clinical practice, no matter what discipline of medicine you are in: the fundamentals of transfusion medicine. This topic often shows up quite frequently on board exams, as well. In this episode, we talk about terms such as “type and screen” and more.

Content:

- What is a "type and screen"?

- What does this process entail?

- What is the difference between this and crossmatching?

- When do we see discrepancies in the antibody screen?

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We are kicking off our intermittent “Heme Consults Series” with a great overview of the approach to leukocytosis, a common question we get on the wards. In this episode, we talk about the initial steps we should take to triage these cases and what we should be thinking about in regards to next steps.

Also - a huge shoutout to one of our listeners who had emailed us and said this is a common question that puzzles them in their work as a hospitalist! If there is something that you’d like to hear us cover in this series, definitely reach out!

Content:

- A refresher on the cell differentiation pathway

- What are the key elements of the history and physical exam?

- What labs should we order?

- A breakdown of the approach to next steps based on the predominant type of WBC

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In episode 046, we discussed the fundamentals of transplant in the treatment of patients with multiple myeloma. This week, we sit down with two incredible hematologists who specialize in transplant to discuss the real-life decision-making that goes into evaluating each patient. We are so excited to welcome two special guests this week, Dr. Shonali Midha and Dr. Amar Kelkar, joining us from the Dana-Farber Cancer Institute in Boston!

Content:

- What goes into determining if a patient is transplant eligible?

- What counseling is provided to patients?

- Approach to melphalan dosing

- How does apheresis work?

- What agents are used to help mobilize stem cells?

- How many stem cells do we need to collect?

- Does how much therapy one has received affect their collection?

- Is there still a role for transplant in today's world?

- Is there a role for an "MRD-adapted" approach to treatment?

- Is there a role for a second transplant in patients who have relapsed?

- Is there a role for allogeneic stem cell transplants in myeloma?

A huge THANK YOU to our guests, Dr. Shonali Midha and Dr. Amar Kelkar, both of the Dana-Farber Cancer Institute!

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We continue our myeloma series, transitioning our discussion from autologous stem cell transplant to maintenance therapy for myeloma.

Content:

- Why do we use revlimid (lenalidomide) maintenance?

- What about in high risk patients?

- What is the role of MRD testing?

- What about daratumumab in the maintenance setting?

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In this continuation of our myeloma series, we discuss all the key principles and data surrounding autologous stem cell transplant in myeloma. We provide a succinct summary of key trials in this space that will give you a deep understanding of the field.

Content:

- What are all these cooperative groups in the studies?

- What are some of the important trials that show us the benefit of autologous stem cell transplant?

- Should transplant be done early or should it be delayed? What does it matter?

- We translate the data/guidelines into what this means for patients in real-life

- How do we approach transplant in high risk patients in myeloma and what are the guidelines about tandem transplant?

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In this episode, we start with a little bit of story time about the history of myeloma treatments and how we got to the present day. We then finish off the episode with how this information helped us treat transplant ineligible patients.

Content:

- What is the history of myeloma treatment? How did we get to where we are today?

- How do we approach treatment in transplant ineligible patients?

- What are the key trials that every fellow needs to know?

- Links to key trials

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In this continuation of our myeloma series, we build on our prior discussion about myeloma pharmacology, this time discussing how to select the optimal regimen for treatment of our patients.

Content:

- What are the phases of multiple myeloma treatment?

- How do we determine transplant eligibility?

- What does doublet, triplet, and quadruplet therapy mean?

- What categorizes "high risk" myeloma?

- What are the current standards of care for transplant eligible patients?

- Where does "CyBorD" fit in for treatment?

- When do we consider adding daratumumab?

- Links to key trials

This episode has been sponsored by Primum. To sign up for a free account, check out: tfoc.primum.co.

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In this continuation of our myeloma series, we begin our discussion about treatment options for multiple myeloma, focusing first on pharmacology. We are so thrilled to have a special guest, Kathryn Maples, PharmD, BCOP who is a clinical pharmacy specialist in Multiple Myeloma at the Winship Cancer Institute of Emory Healthcare in Atlanta, Georgia!

Content:

- What are common drugs we use in "triplet regimens"? "quadruple therapy"?

- What considerations must we take into account when prescribing commonly used medications in myeloma?

- How should we counsel our patients?

- What about supportive care?

- How and when do we make dose adjustments?

- This episode is SO eye-opening about the "behind the scenes" of myeloma care that physicians do not see

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In this continuation of our myeloma series, we discuss the progression of MGUS & smoldering myeloma to multiple myeloma. We also outline how to risk stratify a patient with multiple myeloma and gauge their response to treatment. 

Content:

-What is the natural progression from MGUS to smoldering myeloma to multiple myeloma?

- How do we risk stratify patients with a new myeloma diagnosis?

- What is the role of FISH/karyotype in risk stratification in myeloma?

-How do we gauge disease response in myeloma?

- How do we define disease progression?

- How do we define treatment response?

- What is the role of minimal residual disease (MRD) in myeloma?

Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodes

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In today’s episode, we continue our myeloma series, this time we’ll delve deeper into the spectrum of plasma cell dyscrasias, including defining MGUS, discussing surveillance of MGUS, defining smoldering myeloma (SM). We are slowly inching our discussion towards the diagnosis of Multiple myeloma (MM)!

Content:

- Defining MGUS

- Discussing risk of progression of MGUS to MM

- How to interpret free light chains in renal failure

- How do we monitor MGUS patients?

- When do we do additional testing in MGUS?

- What is smoldering myeloma?

- What are myeloma defining events?

- How do we risk stratify SM patients?

- How do we monitor SM patients?

Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodes

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In the first episode in our highly-anticipated multiple myeloma series, we begin our discussion about introduction to testing/workup for plasma cell dyscrasias and having our initial discussion about monoclonal gammopathy of undetermined significance (MGUS).

Contents:

- What is a plasma cell ?

- What is a plasma cell dyscrasia?

- What is an "SPEP"?

-What is "immunofixation"?

-What are "serum free light chains"?

-Checking UPEP

-Does everyone need a bone marrow biopsy and/or additional workup?

-What is MGUS?

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In this episode, we discuss the acute management of the bleeding patient with acquired hemophilia. Prior to starting this episode, we highly recommend you listen to Episode 036 to review:

- Approach to Hemophilia (physical exam, workup)

- Review coagulation cascade

Contents:

- When to suspect acquired hemophilia?

- Mixing studies in acquired hemophilia patients

- What are Bethesda Units and why are they important?

- How do we treat patients with acquired hemophilia?

- How do we stabilize the acute bleed?

- How do we treat the underlying cause?

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In this episode, we discuss the acute management of the bleeding patient with hemophilia including factor replacement.

Contents:

- Factor replacement guidelines for Hemophilia A vs. Hemophilia B in the patient with an acute bleed

- Management of patients taking emicizumab

- Alternative/adjunctive options for treatment of an acute bleed

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In this episode, we discuss the fundamentals and approaches to chronic management and treatment for patients with known inherited hemophilia.

Contents:

- What is hemophilia?

- How is it inherited?

- How do we grade the severity of one's hemophilia?

- Chronic management of hemophilia

- Mechanism of Emicizumab (Hemlibra)

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In this episode, we break down the initial approach to the evaluation of a patient with a suspected bleeding disorder, particularly in regards to hemophilia, including standardized bleeding assessment tools, the basics of the coagulation cascade, and mixing studies.

Contents:

- "The Fellow on Call" Bleeding assessment!

- Important tips for your physical exam

- How do we think about bleeding disorders?

- What is the basic work-up of a suspected bleeding disorder

- Review of the coagulation cascade

- How to assess an abnormal PT/PTT

Want to review the show notes for this episode and others? Check out our website: https://www.thefellowoncall.com/our-episodes

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Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further.

In this episode, we’ll talk about one of the key hematologic malignancies that you’ll encounter as a fellow, one that requires immediate action to reduce mortality: acute promyelocytic leukemia (APL or APML)

- Acute Promyelocytic leukemia (APL or APML):

**Stay tuned for our upcoming “part two” and “chemotherapy basics” episodes for more information on non-acute management of this disease

**APL is a true hematologic emergency! Although this is a very curable form of leukemia, it is associated with high rates of severe DIC and high mortality in the period immediately following diagnosis

***Untreated, can see pulmonary or cerebrovascular hemorrhage in up to 40% of patients

***10-20% incidence of hemorrhage-related mortality in the initial period

***Statistically significant increase in mortality at 30 days with just a 12-hour delay in initial hematologist consultation

- Disease basics:

** Rare subtype of AML( <10% of cases)

** Driven by translocations involving the retinoic acid receptor alpha (RARA) on chromosome 17, classically with the promelocytic leukemia gene (PML) on chromosome 15 [i.e. t(15;17)]

***Other non-classical translocations exist, but nearly all involve RARA

**Because of this driver mutation, treatment with a specific isoform of vitamin A: all-trans retinoic acid (ATRA) forces promyelocytes to differentiate and ultimately apoptose 

- Initial work up:

**Standard CBC with differential, CMP

** Review smear for characteristic features:

** Large nuclei and scant cytoplasm

** “Folded” appearance to nuclei (like a peach emoji 🍑)

** Auer rods (which tells you blasts are myeloid lineage)

** Heavily granulated cytoplasm (hypergranular form - most common)

***Also a “hypogranular variant,” so like always, make sure to discuss any findings with your friendly neighborhood hematopathologist

**Stat DIC labs:

**PT/aPTT

**Fibrinogen

**Stat PML-RARA FISH (see next section) to look for classic driver mutation and clinch diagnosis

** “Tumor lysis syndrome (TLS) labs”

***LDH

*** Uric acid

**Peripheral flow cytometry

***CD33+, CD 117+

***CD34-, HLA-DR-, CD11a/b/c-

*** Increased side scatter (esp in hypergranular type)

- Acute Management

** Start ATRA: immediate treatment is so important in this disease, and side effect profile is minimal enough that empiric treatment when disease is on the differential is standard of care

**Correct coagulopathies as you detect them 

***Keep fibrinogen > 110 mg/dL

*** Keep INR < 2.0

*** Keep plt > 30k/uL

References:

Gulam Abbas Manji, Samira Khan Manji, Sheetal Karne, and Jeff Chao “Time to ATRA in suspected newly diagnosed acute promyelocytic leukemia and association with early death rate at a non-cancer center institution: Are we meeting the target?” Journal of Clinical Oncology 2012 30:15_suppl, 6615-6615 - impact of treatment delay on 30-day mortality

Eytan M. Stein, Neerav Shukla, Jessica K. Altman “Chapter 20: Acute Myeloid Leukemia” section on acute promyelocytic leukemia ASH SAP 7th Ed pp588-590. DOI: 10.1182/ashsap7.chapter20

Warrell RP Jr, de Thé H, Wang ZY, Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993 Jul 15;329(3):177-89. doi: 10.1056/NEJM199307153290307. PMID: 8515790. - Great review of the basics in NEJM from the early 2000s

Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, Lengfelder E, Döhner H, Burnett AK, Chen SJ, Mathews V, Iland H, Rego E, Kantarjian H, Adès L, Avvisati G, Montesinos P, Platzbecker U, Ravandi F, Russell NH, Lo-Coco F. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019 Apr 11;133(15):1630-1643. doi: 10.1182/blood-2019-01-894980. Epub 2019 Feb 25. PMID: 30803991. - Updated treatment guidelines (more on this in “Part 2” to come)

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Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further. In this episode, we talk all about our fourth hematologic emergency: thrombotic thrombocytopenic purpura (TTP).

Thrombotic thrombocytopenic purpura (TTP):

- Be sure to check out episode 009 on thrombocytopenia for a general approach and differential!

- New anemia and thrombocytopenia should raise concerns for TTP!

Workup:

- Peripheral smear - concern for schistocytes. Look at this first! Example of these cells from ASH image bank here

- ADAMTS13 level - always draw ASAP before any intervention

- Repeat CBC

- Reticulocyte count - will have elevated retic count

- Citrated platelet count

- CMP

- PT, PTT, INR

- Fibrinogen

- Haptoglobin

- LDH

- Viral serologies

Clinical manifestations:

- Fever, Anemia, Thrombocytopenia, Renal (AKI), Altered Mental Status

- If you see this - the patient is in bad shape

Mechanism:

- Tiny blood clots form in the body, causing platelet shearing

- Loss of ADAMTS13 - This protein normally is responsible for chopping up von Willebrand’s factor (vWF)

- In the absence of ADAMTS13, vWF multimers are extra long, therefore interacting with platelets/collagen more and causing activation of platelets and clotting system

- This causes red blood cell shearing due to small vessel microthrombi (brain, kidneys, heart)

- Cytokine release causes fevers

Management:

- Do not reflexively transfuse platelets; can make situation worse

- PLASMIC Score: helps to stratify likelihood of TTP; MDCalc link (https://www.mdcalc.com/plasmic-score-ttp)

Treatment:

- Plasma exchange: replacing ADATMS13-deficient plasma with ADAMTS13-rich plasma

- This is different than plasmapheresis, where we replace plasma with albumin

- Steroids: 1mg/kg prednisone daily to stop auto-antibody (against ADAMTS13) production

- Confirm with ADAMTS13 levels; if <10%, this is confirmatory. This is why this is the FIRST step that we just send off as soon as TTP is suspected

- IF YOU DON’T HAVE ACCESS TO PLASMA EXCHANGE: can administer FFP until you can get them to a center than can do plasma exchange

- Caplacizumab: reserved for patients with severe neurological dysfunction, stroke, or myocardial infarction. Check out the NEJM paper on this (below)!

Microangioathic hemolytic anemia (MAHA):

- Umbrella term for red blood cells shearing in the small blood vessels; TTP is one example of a MAHA

References:

https://ashpublications.org/blood/article/129/21/2836/36273/Thrombotic-thrombocytopenic-purpura - great review article from ASH on TTP

https://www.nejm.org/doi/10.1056/NEJMoa1806311 - NEJM paper on caplacizumab

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Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further. In this episode, we talk all about our third hematologic emergency: heparin-induced thrombocytopenia (HIT)!

Be sure to check out episode 009 on thrombocytopenia for a general approach and differential!

HIT:

- Any time a patient with heparin exposure and now with a new thrombotic event, you need to think about HIT!

What is HIT?

- Type 1: a transient drop in platelets after heparin is started

- Type 2:

**The scary one! Antibody-mediated process

**Heparin molecules bind to platelet-factor 4 (PF4)

**This complex activates platelets, which then further releases more PF4 from the platelets

What is the difference between HIT and HITT?

- HITT is when there is also thrombosis (HIT + Clot)

Why is this more common in the cardiac ICU?

- It is believed that IgM interacts with ultra-long complexes, which heparin is

- Lots of heparin is required for cardiac surgery

- Therefore lots of exposure to heparin increases likelihood, increasing likelihood for IgM to IgG class-switching; HIT is IgG-mediated process

** Remember - since this is antibody-mediated, therefore it takes a few days for the antibodies to form in patient with a new diagnosis of HIT!

How to stratify?

4-T score (MDCalc Link: https://www.mdcalc.com/4ts-score-heparin-induced-thrombocytopenia)

Workup:

- Sent HIT ELISA test in patient with high suspicion

- ELISA just suggests if the HIT antibody is present

- If ELISA positive, then do confirmatory assay, i.e., is this antibody actually doing anything, is the "serotonin-release assay”

- Send 4 extremity dopplers to look for thrombosis

- STOP heparin/heparin-derived products and SWITCH anticoagulant, such as argatroban, fondaparinux, bivalirudin (do not wait for a positive test if your suspicion is high enough!)

If HIT positive:

- Add heparin to their allergy list

- Continue anticoagulation until platelets are recovered (>150K)

- Continue anticoagulation for 3-6 months for patients with HITT

Words of wisdom: If patient comes from outside hospital and starts having decreasing platelets, consider HIT in your differential!

References:

https://ashpublications.org/blood/article/119/10/2209/29530/How-I-treat-heparin-induced-thrombocytopenia- great review article from ASH on HIT

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Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further. In this episode, we talk all about our second hematologic emergency: disseminated intravascular coagulation (DIC) with an added bonus of an intro to thrombotic microangiopathic anemias (TMAs).

Be sure to check out episode 009 on thrombocytopenia for a general approach and differential!

Disseminated intravascular coagulation (DIC):

Workup:

CBC

CMP

PT, PTT, INR

Fibrinogen

Peripheral smear - concern for schistocytes. Example of these cells from ASH image bank: https://imagebank.hematology.org/image/60306/schistocytes?type=upload#:~:text=A%20schistocyte%20is%20present%20in,angles%20and%2For%20straight%20borders.

Basic mechanism of DIC is consumption of clotting factors leading to coagulopathy

Need to be weary of thrombotic microangiopathy: Small blood clots forming in the small vessels leading to endothelial damage, which cause shear stress on the RBCs, which then break down into a schistocyte (AKA triangulocyte or helmet cell)

Examples: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)

Management (our opinion!):

- Repeat coags q4-6 hours initially (but base interval based on patient) NOTE: INR Is NOT a good assessment of “clotting status” in these situations

- Repeat fibrinogen q4-6 hours initially (but base interval based on patient); keep fibrinogen >100 with cryoprecipitate in more stable patients; consider higher thresholds for more acutely ill patients (such as >150)

- Repeat CBC q6-8 hours initially; can provide platelets if low, especially if they are bleeding

- Workup and treatment for trigger of DIC (infection, trauma, medications, etc.)

How does cirrhosis affect data interpretation?

- Use clinical context to determine if labs are acutely abnormal or if they have signs/symptoms to suggest underlying liver dysfunction

- In the acute setting, always just replace what is missing!

How can you tell the difference between nutritional deficiencies vs. consumption (as in with DIC?)

- Factor activity levels! Consider checking: Factor 8 (made in endothelium), Factor 5 (Vit K independent), Factor 7 (vitamin K dependent)

- If all down, then consider DIC

- If Vit K-dependent low, then nutritional deficiency

Reference:

https://ashpublications.org/blood/article/131/8/845/104418/How-I-treat-disseminated-intravascular-coagulation - Great How I Treat article from Blood

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Emergencies happen in hematology and oncology. This is a fact. But how do we manage these emergencies? Look no further. In this episode, we talk all about our first hematologic emergency: immune thrombocytopenic purpura (ITP).

Immune thrombocytopenic purpura (ITP):

Be sure to check out episode 009 on thrombocytopenia for a general approach and differential!

Specific instances where there may be close to undetectable platelet count:

* Lab artifact (clumping)

* Very severe DIC

* Thrombotic thrombocytopenic purpura - though usually higher platelets in these cases

* Heparin induced thrombocytopenia (in very severe cases) - though usually higher platelets in these cases

* ITP

ITP: Diagnosis of exclusion

How to confirm it is ITP?

* Post-transfusion CBC - a repeat CBC 30-60 mins after a platelet transfusion. In ITP, the platelet count will likely not budge. (Not perfect test!)

* Immature platelet fraction (if available) - this will be elevated if mature platelets are being destroyed. (Again - not a perfect test)

Treatment in acute cases:

IVIG 1g/kg daily x2 days + Dexamethasone 40mg daily x4 days

Reference:

https://ashpublications.org/blood/article/106/7/2244/21649/How-I-treat-idiopathic-thrombocytopenic-purpura - Great How I Treat article from Blood

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In our final stop in our Cytopenias series, we discuss the ins and outs of neutropenia. This is another very commonly seen issue in the clinic and in the hospital so most definitely high yield!

Why is neutropenia dangerous?

Prone to infections, especially gut translocation of bacteria

Definition of neutropenia:

NORMAL: WBC 4400-11000 cells/microL; neutrophils make up 40-70% of that

Neutropenia defined by ANC: WBC (cells/microL) x percent (PMNs  +  bands) ÷ 100 

Breakdown:

Neutropenia: ANC <1500 cells/microL

Mild: ANC ≥1000 and <1500 cells/microL

Moderate: ANC ≥500 and <1000 cells/microL

Severe: ANC <500 cells/microL

Agranulocytosis: ANC <200 cells/microL

Approach to workup: HISTORY IS KEY!

Medications; examples of common culprits-  

Chemotherapy 

Methimazole 

Clozapine 

Infections

Any infections due to bone marrow suppression 

Toxins 

Less common causes: 

Congenital

Severe congenital neutropenia:

Diagnosed in childhood; used to be fatal, but now patients living longer because of G-CSF support

10-30% risk of AML in lifetime

Mutations in neutrophil elastase (ELANE) gene or mitochondrial HAX1 gene 

Cyclic neutropenia:

Self-limiting neutropenia that occurs every 2-5 weeks

Spectrum of symptoms: none or oral ulcers/mild infections

Constitutional/ethnic neutropenia:

Mild neutropenia (ANC >1000)

No history of infections

More common in people of Mediterranean and African descent

Duffy Antigen Receptor Complex (DARC) gene mutations in patients of African origin

Benign Familial:

Mild neutropenia

Not linked to particular ethnic group

Unclear underlying etiology

Autoimmune

Primary autoimmune neutropenia rare in adults

Typically secondary autoimmune neutropenia

Due to underlying autoimmune disorder

Seen with SLE and can worsen with flare of disease

Typically mild, seldom needs treatment unless ANC <500

Felty syndrome:  

Rheumatoid arthritis, splenomegaly, and neutropenia

Neutropenia improves with treatment of RA 

Malignancy

Large granular lymphocyte (LGL) leukemia:

Often associated with RA and shares features of Felty syndrome (RA, splenomegaly)

Caused by monoclonal population of large granular lymphocytes

In contrast, in Felty’s: polyclonal or oligoclonal

T-cell LGL is more commonly associated with neutropenia

Requires treatment with methotrexate or cyclophosphamide

Dietary

B12 and folate rarely cause isolated neutropenia

Copper deficiency (gastric bypass): Zinc excess can cause copper deficiencies – ask about denture creams in your history!  

Workup:

History:

Prior CBCs

History of recurrent infections (pneumonia, sinusitis, skin/soft tissue, dental caries)

Ethnic background

Family history

Social history

Dietary history

Surgical history (gastric bypass)

Physical exam:

Adenopathy

Splenomegaly

Skin findings suggesting recent ulcers

Aphthous ulcers

example: https://en.wikipedia.org/wiki/Aphthous_stomatitis

Testing:

CBC with differential

CMP – assess liver and renal function 

Peripheral smear

HIV, Hepatitis serologies

Special scenarios

ANA – if autoimmune disease expected

RF – if autoimmune disease expected

ESR – if autoimmune disease expected; probably not great for inpatient workup

CRP – if autoimmune disease expected; probably not great for inpatient workup

Flow cytometry for LGL

Bone marrow biopsy – mainly for unexplained neutropenia to rule out neoplastic process, such as leukemia, lymphoma, myeloma; if longstanding, likely negative

Management:

Treat the underlying cause

Autoimmune neutropenia –

When to suspect? Workup is negative, but their counts still continue to worsen

Treatment if they have serious complications

Treat with rituximab

LGL-

Responds to low dose methotrexate or cyclophosphamide

Do you give G-CSF?

For patients with recurrent/severe infections or mucosal erosions

Do not treat based on the number alone

Takes time for the growth factors to work

References:

https://doi.org/10.1182/blood-2014-02-482612 - Great “How I Treat” article from Blood!

https://www.uptodate.com/contents/approach-to-the-adult-with-unexplained-neutropenia - UpToDate article written by same author as Blood article

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We continue on our cytopenias journey, this time talking all about anemia. This is a high yield topic for anyone who sees patients, as this is something we will all see.

Determining the acuity of the anemia is the most important first step.

Acute drop in hemoglobin? Consider active bleeding or hemolysis. Dilutional anemia (a drop in hemoglobin following fluid resuscitation) is also on the differential but should be a diagnosis of exclusion.

Remember that we normally transfuse at a hemoglobin level of 7g/dL. If the patient has active cardiac issues, we transfuse at 8g/dL.

Anemia Severity

> 10g/dL = mild

7g/dL to 10g/dL = moderate

4.5g/dL to 7g/dL = severe, especially if acute

1g/dL to 4.5g/dL = these are almost always chronic if patients are conscious. Think about chronic blood loss or nutritional deficiency.

History: Ask about nutrition, melena, hematochezia. Note that a small amount of blood can change the color of the urine, so beware of contributing rapidly developing anemia to hematuria.

Physical Exam: Check the flanks and thighs for bruising. Feel for an enlarged spleen.

Work Up:

Smear—to evaluate for spherocytes, schistocytes, bite cells, etc.

LDH—will be markedly elevated if blood is actively hemolyzing

DAT/Coombs testing—to screen for AIHA, note that there is a high false positive rate

Type & screen

Haptoglobin—sensitive but non-specific marker for blood breakdown

Reticulocyte count

Macrocytic Anemia: Consider copper, B12, folate deficiency, reticulocytosis. Note that chronic zinc excess can cause copper deficiency.

Microcytic Anemia: Consider iron sequestration or deficiency, lead poisoning, thalassemia.

Normocytic Anemia: Usually multifactorial. Consider low erythropoietin level from chronic kidney disease or early iron deficiency anemia.

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One of our most common consults in hematology is teams seeking guidance for workup and management of thrombocytopenia. In this episode, we cover our approach to this hematologic conundrum.

Major Points Covered:

Thrombocytopenia is defined as a platelet count <150K

- Mild: 100-150K

- Moderate: 50-100K

- Severe: <50K

- We get really worried when <20K (risk of spontaneous bleeding)

What to ask in history and in chart review:

- How quickly did the platelets drop - this is just as important as the absolute number; platelets may still be “normal” but have dropped significantly!

- Mucosal bleeding? Menstrual bleeding?

- Rashes?

- Infections/Meds/Toxins?

- Constitutional symptoms

- Weight loss

Our approach to a differential diagnosis - analogous to everyone’s favorite approach to renal AKI: “pre”, “intra,” and “post”:

Pre: Infections/Meds/Toxins

- 1st: HIV, Hepatits

- 2nd: EBV, CMV, Histoplasmosis

Intra: Primary bone marrow failure

Post: Destructions/consumption/splenomegaly (Cirrhosis, too)

- DIC

- ITP

- TTP

- Platelet clumping

Workup:

- Smear - helps to quickly rule in or rule out a lot of the post-BM issues that are emergencies!

- Citrated platelet count (to rule out platelet clumping)

- Repeat CBC

- Coags (PT/PTT/INR)

- Fibrinogen

- HIV serologies

- Hepatitis B/C serologies

- +/- Haptoglobin (note: in liver disease, you can have low haptoglobin)

- Don't send SPEP/IFE!

- If there is no abdominal imaging, consider abdominal ultrasound to evaluate for cirrhosis and/or splenomegaly

References:

https://www.sciencedirect.com/topics/medicine-and-dentistry/hypersplenism (Textbook of Gastrointestinal Radiology, 3rd edition 2008)- 90% of platelets in spleen at one time

https://pubmed.ncbi.nlm.nih.gov/29978544/ (J Thromb Hemostasis 2018)- Platelet threshold for bleeding risk

https://www.bjanaesthesia.org/article/S0007-0912(18)30753-0/fulltext#fig1 (British Journal of Anesthesia 2019)- Perioperative thrombocytopenia (Look at Figure 1)

https://ashpublications.org/blood/article/131/8/845/104418/How-I-treat-disseminated-intravascular-coagulation (Blood 2018) - DIC with normal fibrinogen (Look at case 1, Table 2 shows good diagnostic criteria)

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In Part 1 of our Heme Path series, we break down the logistics and applications of flow cytometry.

Episode contents:

- What is flow cytometry?

- How do we use this to identify cells?

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