CML, leukocytosis, and leukostasis – 8/14/18

Yours truly presented a case of a middle aged man admitted for traumatic rib fracture overnight and found to have a WBC of 368k with cytogenetics consistent with CML!


Clinical Pearls

  • WBC > 100k is most consistent with leukemia.
  • WBC up to 75k can be seen with C diff infection.
  • Leukostasis is most commonly associated with AML > ALL > CML > CLL and defined as hyperleukocytosis with evidence of end-organ damage (CNS, renal, pulm)
    • Hematologic emergency!
    • Treatment is three-fold:
      • cytoreduction: leukapharesis, hydroxyurea, TKI (especially for CML), induction chemo (with other malignancies)
      • FLUIDS
      • prevention of tumor lysis syndrome (another heme emergency): allopurinol, FLUIDS

Differential for leukocytosis:

Blood Cell Lineage

  • Neutrophilia (most common, >7000/mm^3)
    • Infections
    • Stress/trauma
    • Chronic inflammation
    • Meds
    • Leukemias
  • Lymphocytosis (>4500/mm^3)
    • Pertussis
    • Syphilis
    • Viral infections
    • Hypersensitivity reactions
    • Leukemias/lymphomas
  • Monocytosis (>880/mm^3)
      • EBV
      • TB
      • Fungal disease
      • Autoimmune disease
      • Splenectomy
      • Protozoan/rickettsial infections
      • Leukemias

     

  • Eosinophilia (>500/mm^3):
    • Neoplasm
    • Adrenal insufficiency
    • Asthma/atopy
    • Collagen vascular disease
    • Parasites

CML:

  • Refer to this and this prior posts on the blog for all the details!
  • Some details to highlight
    • Smear tends to show lots of immature myeloid cells from many different stages of maturation (some blasts, metamyelocytes, myelocytes, bands, and mature neutrophils)
    • If >20% blasts, then think AML

Leukostasis:

  • Defined as symptomatic hyperleukocytosis and is a hematologic emergency!
  • Mortality rate is can be as high as 40% within the first week of presentation.
  • Clinical manifestations of ischemia primarily in CNS, lungs, and kidneys.  Can also see limb ischemia and priapism.
  • Malignancies at highest risk of leukostasis in order of prevalence:
    • AML (WBC >50k)
    • ALL (WBC >100k, though tends to present with TLS and DIC much more commonly than leukostasis)
    • CML (WBC >100k)
    • CLL (WBC >400k)
  • Treatment:
    • FLUIDS, lots and lots of fluids
    • Cytoreduction: lowers the WBC
      • Leukapharesis: not readily available as it requires a dialysis line and trained nursing staff
      • Hydroxyurea: to lower the WBC
      • Tyrosine kinase inhibitors (especially for CML related leukostasis)
      • Induction chemo (for non-CML related leukostasis)
    • Prevent tumor lysis syndrome:
      • FLUIDS
      • Allopurinol
    • In hemodynamically stable patients AVOID TRANSFUSION – it’s like adding fuel to the fire and can worsen ischemia.

Felty’s Syndrome 8/13/2018

Narges presented a case of an elderly lady with chronic total body pain, found to have rheumatoid arthritis, pancytopenia, and splenomegaly… What could this be? Classic triad for Felty’s Syndrome!

We will start with a brief review of RA:

Rheumatoid Arthritis

  • Epidemiology
    • F : M = 3:1
    • Age of onset usually 50-75
    • Risk factors
      • Smoking
      • Nulliparity
      • Genetics (twins)
    • Extra-articular manifestation (40% cases will have some degree of involvement)
      • Bone: Osteoporosis, esp hip and L-spine
      • MSK: Myositis, muscle weakness
      • Vessels: Vasculitis
        • Neuropathy, pain (MSK vessel inflammation), skin ulceration
      • Skin: Rheumatoid nodule, skin ulcers esp LE, neutrophilic dermatoses
      • Eye: Episcleritis, scleritis, rare
      • Lung: Rheumatoid nodules, parenchymal disease, pleural disease, airway obstruction, pleural effusions (low glucose < 30)
      • Heart: Inc risk of CAD
      • Neuro: Inc risk for stroke
      • Kidney: Higher risk for development of rneal disease
      • Heme: Anemia, neutropenia, thrombocytopenia, inc risk of lymphoma
    • Diagnosis
      • Inflammatory arthritis 3 or more joints
      • RF or CCP
      • ESR/CRP elevation
      • > 6 weeks sx
    • Immunology
      • RF: Sensitivity 80%, Specificity 87%. 5-10% of healthy individuals might have positivity
      • CCP: Sensitivity 76%, Specificity 96%
    • Management (per American College of Rheumatology)
      • Treat ASAP, usually start with DMARD: Screen for latent TB, HBV and HCV prior!
      • HCQ (hydroxychloroquine): Baseline retinal screening and then annual after 5 years of use
      • SSZ (sulfasalazine)
      • MTX (methotrexate)
      • LEF (Leflunomide)
        • Mono
        • Double
        • Triple
        • Combo
      • Biologics
        • Tofacitinib (Janus kinase inhibitor)
        • Abatacept (T-lymphocyte inhibitor)
        • Tocilizumab (IL6 Ab)
        • Rituximab (CD20 MAB)
        • TNF: Etanercept, influximab
      • Steroids

RA Tx

Felty’s Syndrome

  • Epidemiology:
    • Occurs in ~ 1% of patients with RA
    • Not very well understood
    • Associated with HLA-DR4
  • Presentation: Triad of RA, pan-cytopenia, and splenomegaly
    • RA: Typically more severe, erosive, seropositive for RF +/- CP
      • More frequently with extra-articular manifestations
    • Neutropenia: Present in 100%, ANC < 2000 typically, usually with associated anemia + thrombocytopenia. Typically persistent
    • Splenomegaly: Present in most but does not correlate with disease severity
    • Inc risk for hematologic malignancy
  • Diagnosis
    • Clinical: Triad of RA, neutropenia, and splenomegaly
    • Immune: + DsDNA, anti-glucose 6 phosphate isomerase (92%), might have circulating immune complex formation (low complements)

If BM biopsy with lymphocyte infiltration = Large Granular Lymphocyte Syndrome (Pseudo-Felty’s), frequent infections, can progress to LGL Leukemia

Plasmodium vivax 8/9/2018

Narges presented a case of a returning traveler from India, coming in with fever, malaise, and headache several months after returning from India. He was thrombocytopenic on presentation, and a blood smear revealed intracellular parasites within RBCs. He was diagnosed with Plasmodium vivax!

Mal1

Distribution

Mal Distribution

Prophylaxis

Mal Prophylaxis

Treatment + Prophylaxis Overview

Mal TxMal Pearls

Digi-Tox? DigiFab! – 8/8/18

Thanks to Michelle for presenting the case of an elderly man with CKD5 presenting with GI symptoms and bradycardia, found to have regularized A fib consistent with dig toxicity!


Clinical Pearls

  • A “regularized” atrial fibrillation rhythm should trigger work up for digoxin toxicity.  This rhythm is generated because of complete heart block.  So the atria continue to fibrillate but no impulse is getting through to the ventricles.  As a result, a junctional (narrow complex) escape rhythm takes over.
  • Elevated digoxin levels can rule in the diagnosis of dig toxicity but normal levels do not rule it out.
  • Risk factors for dig toxicity include: renal dysfunction, hypokalemia, hypomagnesemia, and hypercalcemia.

Clinical manifestations of dig toxicity:

  • Acute: predominantly GI symptoms (nausea/vomiting, anorexia, non-specific abdominal pain)
  • Chronic: predominantly neurologic symptoms (delirium, confusion, weakness, lethargy, disorientation, vision changes)
  • Cardiac manifestations: can be acute or chronic and of greatest concern!

EKG findings:

  • Most common finding ⇒ PVCs!
  • Other arrhythmias: AVB, atrial tachyarrhythmia, ventricular bigeminy, junctional rhythm, bidirectional ventricular tachycardia (RARE and only a few drugs can cause this)
  • Scooped ST depressions (the famous Salvador Dali mustache)
  • Increased U waves
  • QT shortening

Risk factors for developing toxicity:

  • Renal dysfunction
  • Hypokalemia, hypomagnesemia, hypercalcemia

Treatment:

  • Ingestion 1-2 hours ago? ⇒ activated charcoal
  • Indications for using Digoxin-specific antibody fragments (AKA DigiFab)
    • Severe poisoning
      • life threatening/hemodynamically unstable arrhythmia
      • K > 5
      • Organ hypoperfusion (AMS, renal failure)
      • Other considerations before giving DigiFab:
        • Hyperkalemia ⇒ do NOT treat.  DigiFab will lower levels
        • Hypokalemia ⇒ Treat! DigiFab will make it worse
        • Hypomagnesemia ⇒ Treat!
    • Serum digoxin concentration is irrelevant!
  • You’ve ordered DigiFab but pharmacy is taking too long? ⇒ atropine!

Want more? 

Infective endocarditis – 8/6/18

Thanks to Janhavi for presenting the case of a middle-aged man with no significant PMH presenting with acute onset of malaise, myalgias, and a “stubbed toe,” septic with petechiae on palms and soles, found to have mitral valve endocarditis.


Clinical Pearls:

  • Endocarditis is more common in men (2:1)
  • ~50% of cases of endocarditis occur in people with no known underlying valve disease
  • 80% of cases are caused by staph and strep species
  • TEE is the gold standard for diagnosis and recommended when clinical suspicion for endocarditis is high.  TTE is more helpful to rule out disease when clinical suspicion is low.
  • Indications for early surgery based on this NEJM article include:
    • Heart failure
    • Uncontrolled infection
    • Prevention of embolic events

Duke’s criteria:

Major criteria:

  • Blood culture positive:
    • Typical organism in two separate blood cultures
    • Persistently positive blood cultures
    • Single positive culture for Coxiella
  • E/o endocardial involvement
    • Echo positive for vegetation
    • New valve regurgitation

Minor criteria:

  • Predisposition to IE (i.e. IVDU, prosthetic valve, congenital cyanotic heart disease)
  • Fever >38
  • Vascular phenomena ⇒ arterial emboli, pulmonary infarcts, mycotic aneurysms, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions
  • Immunologic phenomena ⇒ GN, Osler’s nodes, Roth’s spots, RF
  • Microbiologic evidence: positive blood culture not meeting major criteria

Probability of endocarditis:

Definite IE:

  • 2 major, 1 major + 3 minor, 5 minor

Possible IE:

  • 1 major + 1 minor, or 3 minor

Rejected IE:

  • Firmly established alternative diagnosis
  • Resolution of symptoms < 4 days with antibiotics
  • Does not meet definite/possible criteria

Indications for surgery:

  • Valve dysfunction causing heart failure
  • Perivalvular extension with development of abscess, fistula, and/or heart block
  • Fungi or other highly resistant organisms that are difficult to treat with abx alone
  • Persistent bacteremia despite maximal treatment
  • Recurrent embolization with persistent vegetations
  • Large vegetations (>1 cm) with severe valvular regurg
  • S aureus prosthetic valve endocarditis

Indications for early surgery:

  • Heart failure
  • Uncontrolled infection
  • Prevention of embolic events

Complications:

  • Most common cause of death: heart failure
  • Heart block
  • Emboli
    • More likely with s. aureus or S. bovis, veg > 1 cm, or increased veg mobility on echo
    • Antiplatelet therapy initiation is not recommended because of increased risk of hemorrhagic conversion of septic emboli

Want more?

  • Check out this blog post and this great review article in the NEJM.

Catastrophic Antiphospholipid Syndrome, +/- Heparin induced thrombocytopenia & thrombosis, +/- SLE 8/1/2018

Wendy presented a fascinating (and confusing!) case of a patient with history of APS and DVT/PE on chronic warfarin presenting with painful, non-blanching, palpable purpuric rash on the left thigh and lower abdomen found to have thrombocytopenia,  and proteinuria. Skin biopsy revealed small vessel microthrombi. Work up positive SRA, positive ANA, positive DsDNA, low complements… Base on this presentation, the patient possibly has catastrophic antiphospholipid syndrome, with heparin induced thrombocytopenia, and newly diagnosed SLE!

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