American College of Physicians Kansas Chapter Conference October 3, 2013 Ky Stoltzfus, MD University of Kansas Medical Center

Have I got a case for you... Or should it be: Have I got a case for you?

62 year old man with acute promyelocytic leukemia presents with shortness of breath and chest pain.

HPI: Chest pain over left sternum, dull, 7/10 severity, constant, began 4-5 hours prior, not relieved or worsened by any factors. Associated SOB, started at same time, some cough and white sputum. Can't lay flat easily, gets “winded” with walking.

Recent diagnosis of APL Bone marrow hypercellular 95% with 80% blast or promyelocytes Started All-Trans Retinoic Acid (ATRA) therapy the day of admission

During visit he was noted to have WBC 0.7 K/uL Hgb 7.5 g/dL Platelets 13 K/uL Transfused 1 unit platelets

ROS Positive for the following, otherwise negative: Gen: fatigue, malaise, anorexia CV: chest pain Pulm: SOB, cough, sputum production Neuro: dizziness

PMH HTN CAD Type II DM Atrial fibrillation PSH None

Meds tretinoin flecainide simvastatin zolpidem fish oil /omega-3 fatty acids atenolol polyethylene glycol (MIRALAX) pantoprazole

Soc Hx Married Nonsmoker, no EtOH, no illicit drugs Fam Hx Father – prostate CA, died 82yo Mother – CAD, HTN, living 84yo Siblings – healthy No other cancer history

Physical Exam 38.1C P99 R21 BP110/78 O2 87%RA Gen: Sitting, in moderate respiratory distress, alert, oriented x 3 Neck: No carotid bruits, no JVD CV: Irregular, no S3 or S4, no murmur Pulm: Crackles in bilateral bases and mid-lung fields Abd: Soft, nontender, nondistended Extrem: no cyanosis or edema Pulses: 1+ bilateral radial, dorsalis pedal, posterior tibialis

EKG: atrial fibrillation, rate 99, LVH, no ST or T wave changes, no Q waves

Labs: Hgb 7.5, WBC 0.8, Plat 27 32%N, 3%Band, 30L, 4M, 31% blasts Na 131, Cl 101, bicarb 22, lactate 2.1, Cr 1.4, Tbili 1.5, LDH 299 Trop 0.01, BNP 185

What's in your differential diagnosis? Here's mine: CHF exacerbation Transfusion Associated Cardiac Overload (TACO) PNA, atypical TRALI (Transfusion Associated Acute Lung Injury) PE

What would you do next? Diurese patient Possible emperic antibiotics Consider CT chest or VQ scan Contact your blood bank

TRALI American Society of Hematology Education Program ontent/2006/1/497.full

TRALI TRALI is characterized by acute non- cardiogenic pulmonary edema and respiratory compromise in the setting of transfusion Normal CVP and wedge pressure Mimics ARDS

TRALI attributed to donor leukocyte antibodies. Alternate mechanism: “two hit” or “neutrophil priming” hypothesis.

Incidence 1:432 whole blood platelets 1:557,000 red cells Plasma transmission variable (depends on region of the country)

Testing HLA class I or class II, or neutrophil-specific antibodies in donor plasma and the presence of the cognate (corresponding) antigen on recipient neutrophils. Takes weeks to obtain this. TRALI is still a clinical diagnosis.

Follow up Extremely important to notify your blood bank if TRALI is suspected. Donors can tracked. FDA is notified.

Case continued Patient had worsened respiratory failure and subsequent multi- organ failure. He died in ICU on maximal life support.

Summary Suspect TRALI if respiratory symptoms follow transfusion. Keep your differential diagnosis broad. Report suspected cases of TRALI to blood bank immediately.