Hematology Week 8 Summary

Question 36

A 78 year old male is noted to have a haemoglobin of 89g/L with an MCV of 108fL. His neutrophil count is low at 0.9 x 10⁹/L and platelets are found to be 79,000. He feels tired and has no past medical history outside of hypertension, for which he is on hydrochlorothiazide.

Provide an approach for investigating his pancytopenia.

Points of discussion:

1. DECREASED PRODUCTION:
   • Aplasia
     • Congenital (typically identified pre young adult)
     • Acquired
       • Medications (i.e. chemotherapy) or radiotherapy
       • Lymphoproliferative disorders (T-LGL, HCL)
       • Infections (HIV, hepatitis)
       • Toxins (Alcohol)
       • Overwhelming infection
       • Anorexia Nervosa
       • Aplastic Anemia
       • Paroxysmal Nocturnal Hemoglobinuria
   • Hematologic malignancy: MDS, AML, myleoma etc (typically see a hypercellular marrow)
   • Marrow replacement (i.e. granulomatous disease, any cancer)
   • B12 or RBC folate deficiency (typically see a hypercellular bone marrow)
2. INCREASED DESTRUCTION
   • typically due to autoimmune destruction
3. HYPERSPLENISM

Points for discussion include the investigative work up for undifferentiated pancytopenia:

• CBC
• Peripheral blood film
• Reticulocyte count
• B12
• Red blood cell folate
• HIV
• Hep B/C
• ANA (additional connective screen as per history and clinical exam)
• SPEP
• +/- Screen for paroxysmal nocturnal hemoglobinuria (in context of positive hemolytic parameters such as elevated LDH or undetectable haptoglobin)
• Abdominal ultrasound
• Medication and toxin exposure history
• Bone marrow biopsy

Question 37

List the major complications that can result from a new diagnosis of acute leukemia.

Consider points of discussion:

• Tumor Lysis Syndrome:
  • Presence of two or more abnormal laboratory values of either uric acid, potassium, phosphorus, or calcium at presentation, or a 25% change in values from the pre-treatment measurements.
  • Clinical TLS is defined as the presence of laboratory TLS, plus renal dysfunction, seizures, cardiac arrhythmia, or sudden death.
• Hyperleukocytosis (Blast count >100 x 10⁹L): Increased number of blasts in the microcirculation causing decreased tissue perfusion and hemorrhage. Must be managed urgently with cytoreduction
• Disseminated intravascular coagulation and fibrinolysis (particularly in the setting of Acute promyelocytic leukemia)
• Neutropenic fever
• Neutropenic enterocolitis
• Transfusion associated graft versus host disease: all patients should receive irradiated blood products

Question 38

List the indications for a peripheral blood film.

Points of discussion: Indications for a peripheral blood film:

• Anemia NYD, Jaundice NYD
• Thrombocytopenia or neutropenia
• Features of Myeloproliferative neoplasm or lymphoproliferative neoplasm
• Any suspicion of microangiopathic hemolytic anemia
• Suspicion of parasitic disease

J Bain. Diagnosis from the blood smear. N Engl J Med 2005;353:498-507

Question 39

What is the definition of febrile neutropenia, and how should it be managed?

Points of discussion:

• Febrile neutropenia (FN) is defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 h and an absolute neutrophil count <0.5 × 10⁹/l, or expected to fall below 0.5 × 10⁹/l
• Every patient requires:
  • Blood cultures (peripheral and Port/PICC sites)
  • Urine culture
  • CXR
  • +/- culture of other sources of possible infection (eg.. C. difficile collection if diarrhea, throat swab if odynophagia)
• Special considerations:
  • Sinusitis
  • Herpes simplex
  • Herpes zoster
  • Thrush
• Avoid acetaminophen orders which may mask fevers (can order prn acetaminophen if fever already document, please avoid standing acetaminophen orders)
• Avoid suppositories, enemas, or rectal probing while neutropenic

Treatment:

• Neupogen (5ug/kg) until neutrophils at least >0.5 x 10 9/L
• No evidence to support single vs double agent therapy:
  • single agent β-lactam such as cefepime, carbapenem or piperacillin / tazobactam
• There is no role for addition of aminoglycosides unless critically ill with suspected gram negative infection
• VANCO or Linezolid
  • Port / line infection
  • Mucositis
  • MRSA colonization
  • Recent quinolone prophylaxis
  • Prolonged fever

Friefeld A et al. Clinical Practice Guideline for the use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 update by the Infectious Diseases Society of America. CID 2011:

Question 40

Immune thrombocytopenia (ITP) is an acquired disorder characterized by isolated thrombocytopenia with a peripheral blood platelet count <100 × 10⁹/L in the absence of any obvious initiating or underlying cause. It is a diagnosis of exclusion.

It can be idiopathic or secondary (i.e. due to a connective tissue disease, lymphoma etc). Auto-antibodies have been identified against specific platelet glycoproteins.

List the therapies that can be used in ITP.

• Steroids are the first line of therapy with either the use of prednisone (0.5 mg -2 mg/kg) or a short course of dexamethasone (i.e. 40 mg x 4 days). Studies are ongoing of which regiment gives superior results, however a durable platelet response rate is seen in 70% of patients.
• IVIG results in an acute platelet rise usually within 48 hours of use with an effect lasting up to 14 days. RhIg can also be considered in non-splenectomized Rh+ patients with no evidence of hemolysis.
• Splenectomy: controversy exists on when to recommend splenectomy, however this is usually reserved for steroid refractory patients with a 20% relapse rate
• Rituximab: anti-CD20 monoclonal antibody with a durable response at one year seen in 1/3 of patients. The optimal dosing strategy is unknown.
• Thrombomimetics: tpo receptor agonists
  • currently only available once two lines of therapy have been exhausted (including splenectomy), unless contraindicated
  • Romiplostim
  • Eltrombopag

Liebman HA et al. Diagnosis and Management of Immune Thrombocytopenia in the Era of Thrombopoietin Mimetics. ASH Education Handbook 2011.