Cancer Education Day May 13, 2016

Indryas Woldie, MD No relevant conflict of interest

Approach to Cytopenias Objectives: Discuss general approach to cytopenias Discuss common causes of anemia, neutropenia and thrombocytopenia Discuss cytopenia associated conditions that need urgent referral/management

Case I. 27 years old woman presents with fatigue and lab showed hemoglobin of 70gm/l, normal platelets, normal WBC with differential. Case II. 27 years old woman presents with fatigue and bruising and lab showed hemoglobin of 70gm/l, platelets of 25K.

Isolated cytopenias are usually indicative of less serious diagnosis than bi or pan cytopenia. Questions to ask when seeing someone with cytopenia: – Isolated or more than one lineage? – Severity? – Duration and change in time? – Co-morbidity/medications? – Associated symptoms?

Anemias Etiology: I) Blood loss II)Increased destruction -hemolytic anemias III)Decreased production -nutritional deficiency -bone marrow infiltration -aplastic anemias -Inflammation (ACI)* -medications RBC Indices – MCV – MCHC – MCH I)Normocytic – normochromic (Normal MCV and MCH) II)Microcytic, hypochromic (MCV <80, MCHC <32) I)Macrocytic (MCV >100)

Case I. 27 years old woman at 32 weeks for gestation presents with fatigue and lab showed hemoglobin of 78gm/l. MCV 65, RDW 25 MCHC 30, platelets 480K WBC: 7500, with normal differential. Q: In addition to reviewing her peripheral smear, what additional lab work will confirm diagnosis? Q: How will you treat her?

27 years old woman has from Greece has a CBC and lab showed hemoglobin of 110gm/l. MCV 65, platelets 250K, WBC: 7500, with normal differential. She has been on iron pills for the last 2 years with no change in her hemoglobin or MCV, has constipation and nausea. Q: What is the most helpful recommendation for the patient? Peripheral smear showed (next page)

Q: What is the most likely diagnosis? Q: How can we confirm the diagnosis?

Case 3: 65 years old man with history of CLL on conservative follow up comes with worsening fatigue over the past week. CBC: Hgb 62 gm/l (was 110 a week ago), MCV 110, RDW 25, Platelets 129K, WBC 150K ANC 9.5, ALC 138. Attempt to type and crossmatch was unsuccessful. Q: What additional labs will you get ?

Hemolytic work up: Reticulocyte count LDH Haptoglobin Bilirubin (Indirect)* Direct coomb’s test (if positive [IgG], confirms AIHA, steroid usually effective) Coomb’s negative hemolytic anemia (hemolytic panel positive but negative Coomb’s test). – Hemoglobinopathies (SSA, thalassemias..) – Structural abnormalities (spherocytosis) – MAHA (TTP, aHUS, mechanical valve) – PNH

MAHA/TTP: – Medical emergency – No need for traditional pentad as long as patient has MAHA (schistocytes + HA) and thrombocytopenia. – Immediate referral for plasma exchange(PE). – Obtain ADAMSTS13 activity ( result is not needed for initiation of PE) – Avoid platelet transfusion

Case: 65 years old man presented with fatigue. He had history of gastric bypass surgery 8 years ago. Labs showed: Hgb 85gm/l, MCV 88, RDW 28, Platelets 75K, LDH 330, Bilirubin (mildly elevated indirect), low haptoglobin. WBC 2.4 ANC 1.8 Which lab test/tests will be most relevant?

Vitamin B12 was low at 120. Folate normal. Do we need to send for MMA? Patient was treated with B12 supplementation and repeat labs after 3 months showed: – Hgb 98, MCV 77, RDW 25, Platelet 480, WBC normalized. What next?

You sent for ferritin and was found to be low at 5, with low iron saturation. He was started on iron supplement, ferrous sulfate TID. Develops severe constipation, nausea and occasional vomiting. Dose reduced to one tab daily with better tolerance. CBC normalized and iron supplementation continued. Any thing else?

Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Diego et.al; Blood Oct Continuous line is for first dose Broken line is for second dose

Thrombocytopenia:

– Mild (80-150K)-no risk of bleeding – Moderate (20-80K)-minor bleeds (bruise..) and bleeding with surgery/trauma – Severe (<20K)-spontaneous bleeding possible

Thrombocytopenia: causes I)Increased destruction: -Immune (ITP, drug induced) II) Decreased production -Nutritional deficiency (B12, folate) -Bone marrow (leukemia, aplastic anemia) III) Sequestration -Splenomegaly (cirrhosis)

Case : 25 y/f has URTI like symptoms, bruises for 2 weeks and CBC showed : WBC 4.5, ANC 3.5, Platelets 3K, Hgb 122gm/l. Exam showed generalized LAP, few scattered bruises Peripheral smear was unremarkable except for thrombocytopenia (no platelet clumping). Q: What labs do you want to order?

Hepatitis profile negative (hep B and C) ANA 1:32 HIV: positive ELISA and HIV RNA You made a diagnosis of HIV associated ITP. Which of the following is not effective treatment option for this patient? A)Platelet transfusion B)IVIG C)Steroid (1mg/kg) D)Treatment of HIV/HAART

Neutropenia: Classification – Mild – Moderate – Severe <500* – Profound <100 Etiology: – Infection – Decreased production – Immune – Drugs

Case : 33y/m established new family physician visit and had a routine CBC that was unremarkable except for mild neutropenia (ANC 1200). -on further history he said he was told he has low neutrophils on several occasions over the past 6 years. -he denied repeated infections -family history was positive for low neutrophil count in his mother. What is the most likely diagnosis? Any additional work up?

Case: 55y/m is on chemotherapy for CLL. He was last treated 10 days ago. He presented to your office c/o chills and myalgia and LLQ discomfort. Exam showed T-39 Celsius, BP 109/65 HR 112, LLQ tenderness. Stat CBC showed Hgb 110, ANC 50 and Plts 85k What is the next best step in management? A)Oral Levofloxacin and follow up in a week. B)Follow up with his oncologist next day C)Draw blood culture and send for urgent admission for IV antibiotics D)Oral Levofloxacin and daily neupogen

Bi/pancytopenia

Usually serious causes: – Bone marrow : Acute leukemia Aplastic anemia MDS Myelofibrosis – Acute infection

Case: 65 y/m presented with bruises and fever as well as nose bleeds. He has a routine visit 3 weeks ago and had normal CBC at that time. CBC now shows: Hgb 77, WBC 2.7, ANC 0.7, Few immature granulocytes reported, Platelets of 25K. Electrolytes ok. PT/INR 1.4, aPTT 36 sec, Fibrinogen 108. Q: What should be the most important diagnostic consideration in this patient? Q: What will you do next?

Overall survival of APL patients treated with ATRA in combination with anthracyclines in Brazil. (A) Analysis of all patients. (B) Analysis excluding patients who died during induction. Blood, Dec 2009.

63 y/f who was treated with chemotherapy and radiation for breast cancer 10 years ago was found to have the following labs on routine CBC. – Hgb 110, MCV 104, WBC 2.3, ANC 1.2, Platelets 68. – Vitamin B12 and folate normal. – Labs 6 months ago showed Hgb 112, MCV 104, WBC normal, Platelets 88. You are concerned about long term complications of chemotherapy (MDS). The best was to confirm the diagnosis is: A) PB flow cytometry B) BM aspiration and biopsy C) Peripheral smear

Thank you!