2  Outpatient Hematology Topics

Key Points
  • ASH Choosing Wisely: evidence-based appropriateness for hematology procedures & tests
  • Thrombocytopenia: individualize management per cause & risk factors
  • Pseudothrombocytopenia: rule out w/ blood smear; screen for HBsAg/HCV/HIV at presentation
  • ITP: no confirmatory test; diagnosis is exclusionary
  • CLD + thrombocytopenia: ↓ TPO, splenic sequestration; TPO-RA (avatrombopag/lusitromobpag) pre-op
  • Bleeding disorders: detailed hx + coagulation studies → factor testing; ~40% diagnostic yield
  • Hard/fixed/enlarged LN: r/o malignancy; excisional biopsy > FNA
  • Splenomegaly: physical exam + imaging per scenario

2.1 The Role of the Hematology Consultant

  • Committee service & standardization
  • Guideline development
  • EMR optimization
  • Multidisciplinary communication
  • Cost-effective care; avoid unwarranted diagnostics & treatment
  • Complex consultations may require subspecialty assistance

2.2 Thrombocytopenia

2.2.1 Definition & Initial Evaluation

  • Thrombocytopenia: plt <150K/μL
  • Evaluation: review labs for trends, medication hx, severity, physical exam (LAD, splenomegaly, rashes, bleeding stigmata), assess bleeding (location, severity, duration, prior transfusions)
  • Mild thrombocytopenia (100K–150K): common in many disorders; requires careful exam
Clinical Pearl: Pseudothrombocytopenia Screening
  • Pseudo-thrombocytopenia: EDTA clumping → review blood smear
  • Secondary causes: infection, drugs, autoimmune, CLD, malignancy

2.2.2 Thrombocytopenia of Chronic Liver Disease

  • Baseline: 40K–120K/μL
  • Mechanisms: ↓ TPO, splenic sequestration (30% plt mass), ↑ coagulopathy
  • Bleeding risk: low despite low plt count; assess bleeding tendency
  • Splenic flow: assess w/ Doppler U/S for enlargement & portal flow

Pre-op treatment: - TPO-RA agents: avatrombopag OR lusitromobpag (short course pre-procedure) - Evidence: ADAPT-1, ADAPT-2 (phase 3 RCT); efficacy maintained, minimal AEs

2.2.3 Thrombocytopenia Associated w/ Infection

  • Transient during systemic infection; assess outpatient vs. hospitalized
  • Mechanisms: ↓ production, ↑ destruction, immune-mediated
  • Specific infections: megakaryocyte infiltration, hemophagocytic syndrome
  • Lab screen: HIV, HBV, HCV, SARS-CoV-2, EBV upfront; consider CMV
  • Scope: critically ill patients outside outpatient domain

2.2.4 Thrombocytopenia Associated w/ Medications

  • DITP: drug-induced thrombocytopenia
  • Severe: sulfa antibiotics
  • Mild: anticonvulsants, NSAIDs
  • Management: review meds w/ pharmacy, eliminate offender if possible
  • Transfusion: indicated if vital organ bleeding

2.3 Approach to the Patient w/ Excessive Bleeding

Key steps: - Detailed personal & family hx (location, frequency, age of onset, impact) - Physical exam for bleeding/bruising - Lab tests quantify tendency - Reassess if high suspicion & initial labs normal

2.3.1 Importance of Medical History

  • Bleeding episodes: specific pattern, location (easy bruise, epistaxis, gingival)
  • Triggers: trauma, surgery, dental, menstruation
  • Timing: especially mucous membrane bleeding
  • Congenital: often childhood onset w/ recurrent infections; cyclic neutropenia = 21-day periodicity (a/w large granular lymphocyte leukemia or AML)
  • Hemostasis challenges: surgery, dental, trauma → guides lab workup

2.3.2 Screening Tests for Bleeding Disorders

  • Platelet count, PT, aPTT (initial screen)
  • Mixing study: corrects → factor deficiency; fails to correct → inhibitor
  • Factor VIII assay: for acquired hemophilia
  • ISTH-BAT: self-administered validated bleeding assessment tool (paper/electronic)
  • Sensitivity: screening tests unreliable; clinical suspicion critical
  • Specimen handling: affects result; verify meds don’t interfere
  • PFA-100: 90% sensitive severe PLT dysfunction (vWD), <80K plt; variable w/ antiplatelet drugs
  • Diagnostic yield: ~40% in hereditary mucocutaneous bleeding

2.4 Leukocytosis

  • Common concern: malignancy, but most = benign neutrophilia
  • Etiologies: smoking, cardiac disease, psoriasis, pneumoconiosis, chronic infection, steroids
  • Worrisome findings: ↑ monocytes/plt (MPN), persistent lymphocytosis (CLL), blasts/immature RBC
  • BM workup: if concern for primary process → biopsy/aspirate, flow, cytogenetics, NGS

2.4.1 Leukopenia & Neutropenia

  • Leukopenia: ↓ WBC w/o blasts; ANC <4.5K/μL
  • Neutropenia classification:
    • Mild: ANC 1–1.5K/μL
    • Moderate: ANC 0.5–1K/μL
    • Severe: ANC <0.5K/μL
  • Congenital: childhood onset w/ recurrent infection
  • Cyclic neutropenia: 21-day periodicity; a/w large granular lymphocyte leukemia or AML
Leukocytosis: etiologic considerations
Leukocyte Subtype Key Etiologies
Neutrophilia Infection, inflammation (Crohn, UC, rheumatologic), Sweet syndrome, malignancy, trauma/burn, severe stress, asplenia, smoking, TB, hepatitis, hereditary, obesity, corticosteroids, β-agonists, lithium, G-CSF/GM-CSF, MPN (CML/PV/ET), eclampsia, thyrotoxicosis
Monocytosis TB, syphilis, endocarditis, Crohn, sarcoidosis, SLE, infectious mono, CMML, CML, pregnancy
Eosinophilia Allergy, asthma, parasites, aspergillosis, histoplasmosis, HIV, immunodeficiency, drug rxn, vasculitis, adrenal insufficiency
Lymphocytosis Mono syndrome (EBV/CMV), primary HIV, Bartonella (cat scratch), toxo, reactive LGL, CLL, MBL, post-splenectomy

Neutropenia management: - Asymptomatic: often no treatment needed - G-CSF/GM-CSF: consider clinical context; reserve for ANC <500 or with fever/chemo - Drug-induced: clozapine, metamizole, TMP-SMX cause agranulocytosis (BM suppression)

2.5 Lymphadenopathy

  • Normal in adults: inguinal <1.5 cm palpable; others impalpable (need imaging)
  • Deep nodes: CT/MRI for detection
  • Malignancy stigmata: hard, fixed, nontender, asymmetric + B sx (fever, night sweats, weight loss)

2.5.1 Causes

Causes of lymphadenopathy
Localized Generalized
Bacterial, fungal, TB, atypical mycobacteria Mono syndrome (EBV/CMV/primary HIV)
Bartonella henselae (cat scratch) Viral (EBV, CMV, primary HIV, other viruses)
Sarcoidosis, Langerhans cell hist Infections: TB (miliary), Bartonella, toxo, tularemia, leptospirosis, Lyme, syphilis
PTGC, inflammatory pseudotumor Fungal: histoplasmosis, coccidioidomycosis, cryptococcosis
Malignancy (NHL, HD, CLL, mets) Rheumatologic: SLE, RA, Still disease
Other: sarcoidosis, Langerhans cell hist, phenytoin, serum sickness, ALPS, HLH
Lymphomas: indolent NHL, HD, CLL
Rare: Rosai-Dorfman, multicentric Castleman, Kikuchi, Kawasaki, AILD
Clinical Pearl: Hard LAD = Malignancy Until Proven
  • Hard/fixed/nontender + B sx → rule out malignancy
  • Excisional biopsy > FNA for lymphoma diagnosis (preserves architecture)
  • Biopsy workup: flow, cytogenetics, molecular testing, IHC

Initial evaluation: - Review medications (phenytoin, serum sickness) - Labs: ANA, RF, HIV, infectious serologies - Localized: observe 2–3 weeks if no red flags - Constitutional sx: urgent evaluation

2.6 Splenomegaly

  • Normal: ≤13 cm, not palpable
  • Exam: measure below costal margin; percussion dullness Traube’s space
  • Imaging: U/S ± Doppler assess size, architecture, splenic & portal flow

2.6.1 Causes

  • Infections: EBV (infectious mono), hepatitis, TB, atypical mycobacteria
  • Malignancies: lymphoma, primary myelofibrosis, CML, CLL
  • Infiltrative: Gaucher disease (↓ glucocerebrosidase), other storage disorders
  • Hemolytic: autoimmune hemolytic anemia, hereditary spherocytosis
  • Rheumatologic: SLE, RA, Felty syndrome
  • Cirrhosis & portal hypertension: portal HTN → sequestration
  • Travel/exposure hx: coccidioidomycosis, leprosy, Bartonella, toxo (undercooked meat)
  • B sx + splenomegaly: r/o infection, malignancy

2.6.2 Hypersplenism & Sequelae

  • ~1/3 plt sequestered normally; equilibrium w/ circulation
  • Splenomegaly → ↑ sequestration → cytopenias (hypersplenism)
  • Apparent thrombocytopenia: low plt but normal total mass & survival → NO bleeding typically, transfusion rarely needed
  • CLD + splenomegaly: combined ↓ TPO + sequestration + coagulopathy → worse prognosis

Splenectomy indications: - Recurrent cytopenia or pain - Pre-op: can improve plt count for safer surgery - Post-splenectomy: aggressive VTE prophylaxis (periop/postop); prevent infection w/ vaccinations (pneumococcal, meningococcal, Hib)

2.7 Bibliography

Arshad N, Gianmill E, Erygh G, et al. Hemorrhage before procedures in patients w/ untreated & treated thrombocytopenia. N Engl J Med. 2015;367:716–724.

American Society of Hematology. Choosing Wisely. Available at: https://www.hematology.org/Patients/Choosing-Wisely. Accessed 24 March 2024.

DeForest M, Galei J, Khmer S, et al. Generation & optimization of self-administered bleeding assessment tool in adults. J Thromb Haemost. 2015;13(3):e438–e388.

A Practical Guide to Hemostasis: Platelet Transfusion PFA 100 & PFA 200. Available at: https://www.practical-haemostasis.com. Accessed 19 March 2024.

Fradkov E. Clinical utility of the PFA-100. Semin Thromb Hemost. 2008;34(9):709–733.

Hay KW, Hayward PA. Comparison of scores from the ISTH-BAT & self-ISTH-BAT in adolescent biological females w/ heavy menstrual bleeding. J Pediatr Adolesc Gynecol. 2019;32(4):359–365.

A Practical Guide to Hemostasis: Platelet Transfusion. Using PFA. Available at: https://www.practical-haemostasis.com/Bleeding-Disorders/PFA/PFA-100.html. Accessed 9 March 2024.

Quieros T, Guyondes M, Pravo G, et al. High prevalence of bleeding of unknown cause among patients w/ inherited mucocutaneous bleeding. J Prospective study of 250 patients & 209 controls. Haematologica. 2007;92(8):357–365.

Rockeltgeren E, Ekeraro A, Aubert J, et al. ISTH SSC bleeding assessment tool: a standardized questionnaire & a proposal for a new bleeding score in the assessment of inherited bleeding disorders. J Thromb Haemost. 2010;8(12):2893–2905.