Anna M. Dapul, M.D. Kathleen B. Miranda, M.D. August 12, 2010.
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Transcript of Anna M. Dapul, M.D. Kathleen B. Miranda, M.D. August 12, 2010.
Anna M. Dapul, M.D.Kathleen B. Miranda, M.D.
August 12, 2010
To present a case of pneumonia in a Chronic Lymphocytic Leukemia patient;
To discuss the infectious complications in CLL patients
To discuss the syndrome of Transfusion-related Acute Lung Injury
E.B.71/male
Difficulty of breathing
Admitted
1 week PTA
2 days PTA
1 day PTA
Few hours PTA
Cough self-medicated w/unrecalled antibiotics
Colds, watery nasal discharge
Productive cough Fever T=39C
OPD HSP consult, given Paracetamol, Levofloxacin 750mg OD
DOB ER
General: (-) weakness, (-) weight changes, (-) night sweats, (-) fever, (-) syncope
Skin: (-) pruritus, (-) rashes, (-) easy bruising, (-) telangestasia, (-) spiderangiomatas
HEENT: (-) headache, (-) dizziness, (-) BOV, (-) eye redness, (-) epistaxis, (-) deafness, (-) ear discharge, (-) bleeding gums, (-) oral sores, (-) hoarseness, (-) neck pain, (-) limitation of motion
Respiratory: (-) hemoptysis, (-) PND Cardiovascular: (-) chest pain, (-)
palpitations, (-) orthopnea, (-) paroxysmal nocturnal dyspnea
Gastrointestinal: (-) dysphagia, (+) early satiety, (-) jaundice, (-) nausea, (-) vomiting, (-) hematemesis, (-) constipation, (-) diarrhea
Genitourinary: (-) polyuria, (-) hematuria, (-) nocturia, (-) oliguria, (-) dysuria
Extremities: (-) joint pains, (-) swelling Neurologic: (-) seizures, (-) tremors, (-)
involuntary movements Hematologic: (-) dizziness, (-) bleeding, (-)
easy bruising Endocrinologic: (-) occasional excessive
sweating, (-) polyphagia, (-) polyuria, (-) polydipsia
Chronic Lymphocytic Leukemia(B-Cell)-2007◦On intermittent oral chemotherapy with
Chlorambucil, Prednisone, Folic Acid, and Multivitamins
Hypertension x 5years◦On Amlodipine 10mg tab OD ◦Metoprolol 100mg OD◦Usual BP: 120/90; highest BP140/90
No known allergies; no previous surgeries
Hypertension- mother
SOCIAL HISTORYSOCIAL HISTORY 20 pack year smoker Occasional alcoholic beverage drinker
Conscious, coherent BP= 130/80 HR=107 RR=18 T=36.8C O2
SAT = 94% (room air) Pale palpebral conjunctivae, anicteric
sclera, no tonsillopharyngeal congestion, no cervical lymphadenopathy, no oral thrush
Equal chest expansion, no retractions, bibasal crackles, no wheezes
Adynamic precordium, normal rate, regular rhythm, distinct S1 and S2, no appreciated murmurs
Flabby abdomen, soft abdomen, normoactive bowel sounds, no tenderness, no splenomegaly
No gross deformities of the extremities, pulses full and equal, no cyanosis, no edema
71/male Dyspnea Fever Productive cough Known case of
Chronic Lymphocytic Leukemia ~3years
Tachypnea Pale palpebral
conjunctivae Bibasal rales
Community Acquired Pneumonia in an Immunocompromised Host
Chronic Lymphocytic Leukemia Hypertensive Atherosclerotic
Cardiovascular Disease
Immunocompromised host
◦ Alteration in phagocytic, cellular, or humoral immunity
◦ Increased risk for an infectious complication or an opportunistic process (ie lymphoproliferative disorder or cancer)
◦ Alteration or breach of skin or mucosal defense barriers that permits microorganisms to cause either a local or systemic infection (ie indwelling catheters, burns)
Pizzo, P. Fever in Immunocompromised Patients.NEJM.1999;341: 893
Host Defect Disorders or TherapyAssociated With Defect
Likely Pathogens
Defective PMNs
Neutropenia Acute leukemia, aplastic anemia,cancer chemotherapy
Gram-negative bacteria,Staphylococcus aureus,Aspergillus sp, Candida sp
Defective chemotaxis Diabetes mellitus S. aureus, gram-negativeaerobes
Defective intracellularkilling
Chronic granulomatous disease
S. aureus
Defective alternativepathway
Sickle cell disease Streptococcus pneumoniae,Haemophilus influenzae
C5 deficiency Congenital disorder S. pneumoniae, S. aureus,gram-negative bacteria
Cell-mediated immunodeficiency
(T-cell deficiency ordysfunction)
Hodgkin lymphoma, cancerchemotherapy, corticosteroidtherapy
Mycobacteria, viruses(herpes simplex virus,cytomegalovirus),Strongyloides sp, opportunisticfungi (Aspergillus, Mucor,Cryptococcus spp),Nocardia sp, Toxoplasma sp
AIDS Pneumocystis jiroveci,Toxoplasma sp,cytomegalovirus, herpes simplexvirus, opportunisticfungi (Aspergillus, Mucor,Cryptococcus spp), mycobacteria
HumoralImmunodeficiency
(B-cell deficiency ordysfunction)
Multiple myeloma,Agammaglobulinemia
S. pneumoniae, H. influenzae,Neisseria meningitidis
Selective deficiency: IgA, IgG,IgM
S. pneumoniae, H. influenzae
Hypogammaglobulinemia
P. jiroveci, cytomegalovirus,S. pneumoniae, H. influenzae
Disease affecting neoplastic B cells
Mostly asymptomatic
Common symptoms: lymph node enlargement, constitutional symptoms, bone marrow failure
Mainly affects elderly (median age=72 yrs)
Clinical diagnosis: absolute lymphocytosis with lower threshold of >5000 mature-appearing lymphocytes/uL
STAGING OF TYPICAL B CELL LYMPHOID LEUKEMIA
Stage Clinical Features Median
Survival,Years
RAI System
0: Low risk Lymphocytosis only in blood and marrow >10
I: Intermediaterisk
Lymphocytosis + lymphadenopathy +splenomegaly ± hepatomegaly
7
II
III: High risk Lymphocytosis + anemia 1.5
IV Lymphocytosis + thrombocytopenia
Stage Clinical Features MedianSurvival,Years
Binet System
A Fewer than three areas of clinicallymphadenopathy; no anemia orThrombocytopenia
>10
B Three or more involved node areas; noanemia or thrombocytopenia
7
C Hemoglobin </= 10 g/dL and/or platelets<100,000/μL
2
STAGING OF TYPICAL B CELL LYMPHOID LEUKEMIA
Inherent Immune Defects in patients with Chronic Lymphocytic Leukemia
HypogammaglobulinemiaInhibition in B-cell proliferationCell-mediated immune defects
Functional abnormalities of T-lymphocytes, nonclonal CD5– B lymphocytes
Abnormalities in T-cell subsets, with a decreased CD4/CD8 ratioExcessive T-suppressor and deficient T-helper cell functionDownregulated T-cell functionDefects in NK-cell, lymphocyte-activated killer cell activityReduced T-cell colony-forming capacityDefective antibody-dependent cytotoxicityDefective delayed hypersensitivity responses
Defects in complement activityReduction in complement component levelsDefects in complement activation and binding
Neutrophil defectsDefects in neutrophil function (phagocytic, bactericidal activity, chemotaxis)Reduced absolute neutrophil count
Monocyte defects (deficiencies in β-glucuronidase, lysozyme,myeloperoxidase)Potential mucosal immune defects
Chills, bibasal rales ECG: sinus
tachycardia Hypotensive
episode
Admitted under ID service
Oxygen at 4 LPM Referred to:
nephrology, cardiology, hematology services
dopamine drip-5mcg (200mg/100ml)
Hgb 7.9
Hct 23.4
WBC 100.16
Segmenters 3
Lymphocytes 92
Prolymphocytes 2
Monocytes 3
Platelets 175k
ANC 3004.8
CXR (3/30) cardiomegaly with pulmonary congestion
Infectious Disease◦Blood gs/cs,
sputum gs/cs, urine gs/cs, urinalysis
◦Piperacillin-Tazobactam 2.25g IV q8 hours
Cardiology◦2D ECHO, specM,
Trop I/T, D dimer
Hematology◦Prepare 2u pRBC◦Start
Chlorambucil 2mg tab TID
Nephrology◦ABGs, Na, K, crea,
Mg, Ca◦For central line
insertion◦Furosemide 40mg
2tabs BID◦Limit OFI
1-1.5L/day
Na 129
K 3.4
Bun 23.83
Creatinine 2.57
Trop I 0
Trop T 0
D dimer 1264.31
Calcium 7.9
Magnesium 1.82
ABG O2 AT 2LPM
pO2 80
pH 7.5
pCO2 33.9
HCO3 26.2
02 SAT 96.8
B.E. + 3.6
TCO2 27.3
S> no complaints, comfortable at o2 of 2 LPM; post 1 unit PRBC
O> BP90-110/60-70 on dopamine drip, HR=95-110, crackles mid-base L>R, T=38.2C
I&O=1275 vs 1400
Hgb 9.2
Hct 25.5
WBC 35.47
Promyelocyte 1
Segmenters 4
Lymphocytes 94
Basophils 1
Platelets 130k
ANC 1418.8
CXR (4/1) clearing of pulmonary congestion, hazy infiltrates with some cystic lucencies in LLL probably due to pneumonia with underlying bronchiectasis
2D Echo: IVSH, NWMC, EF=63%, mild MR, reversed mitral E/A ratio and prolonged IVRT indicative of decreased LV relaxation
Blood, urine, sputum CS: no growth x 24hrs
UA: normal
Piperacillin Tazobactam – day1
Infections
Hematologic abnormalities: ◦ anemia (autoimmune hemolytic anemia)◦ pure red cell aplasia◦ thrombocytopenia
Richter Syndrome or Richter transformation◦ refers to the transformation of CLL into an
aggressive large B-cell lymphoma
Leading cause of mortality in 25-50%
Pathogenesis of infection is multifactorial
Major risk factor: inherent immune defects and therapy-related immunosuppression
Front-line treatment usually involves purine analogue such as Fludarabine in combination with Cyclophosphamide combined with monoclonal antibodies such as Rituximab
Chlorambucil is considered standard treatment for elderly patients due to easier administration and less immunosuppression
Zenz, T et. al. Treatment of CLL in Older Patient. Medscape CME Oncology.2010
The Impact of Chronic Lymphocytic Leukemia Therapy on the Spectrum of Infection
Type of treatment Spectrum of infection
Single-agent alkylator therapy (+/- corticosteroids)
Common bacterial pathogens (streptococcal/staphylococcal spp., enteric Gram-negative organisms)
Purine analogs Candida, Aspergillus, Herpesviruses, Pneumocystis
Monoclonal Antibodies
Rituximab No definitive change in spectrum of infection
Alemtuzumab Herpesvirus, including cytomegalovirus, Candida, Aspergillus, Pneumocystis
S> awake, conversant, no febrile episodes, D2 piperacillin-tazobactam
O> BP90-110/60-70 HR=90-100, crackles L>R, Total I&O= 4030 vs 3500 on furosemide 80mg bid
Blood CS: no growth x 48 hours
Urine & Sputum CS: no growth x 48hrs
Hgb 11.1
Hct 30.5
WBC 47.62
Segmenters 13
Lymphocytes 86
Prolymphocytes 1
Platelets 139k
ANC 6190.6
CXR (4/2) complete clearing of pulmonary congestion, rest of the chest findings are unchanged
Piperacillin-Tazobactam shifted to Levofloxacin 500mg PO x 1 dose then 250mg PO q48 hours
Started Metronidazole 500mg PO q8 hours Furosemide decreased to 80mg PO q24
hours Patient referred back to prior hematologist
De-escalation of initial empiric broad-spectrum antibiotic to oral agent based on available laboratory data is recommended once the patient is ◦ clinically improving◦ hemodynamically stable ◦ functioning gastrointestinal tract
Community-Acquired Pneumonia Clinical Practice Guidelines 2010 Update
One study that specifically focused on levofloxacin found proactive conversion to the oral formulation reduced length of stay by 3.5 days and saved medication/supply costs
Another recent study documented that early conversion from IV to PO therapy in CAP decreased length of stay by almost 2 days, while having no negative effects on mortality or clinical cure
Kuper, K. Intravenous to Oral Therapy Conversion. Competence Assessment Tools for Health-System Pharmacies 4th Ed. 2008:347.
S> awake, coherent, fever
O> Tmax=38.3C BP90-120/60-70 on dopamine, HR=90-120, Total I&O 2565 vs 3400
UA: normal Repeat blood CS taken
Furosemide held Paracetamol as
needed for fever Cefepime 1gram q24
hrs
CXR (4/3) taken in poor inspiratory effort, increase in left lower lung infiltrates
S> denied chest pain, dob
O> BP90-108/60-70 on dopamine, HR=100-115, Tmax=38.5C, 02sat=88% @ 4lpm
Total I&O= 2859 vs 2000
Blood CS: no growth x 24 hours
ABG taken
Hgb 11.3
Hct 32.3
WBC 77.72
Segmenters 12
Lymphocytes 86
Monocytes 2
Platelets 140k
ANC 9326.4
ABG 02 at 5 LPM
pO2 51.6
pH 7.51
pCO2 32.7
HCO3 25.6
O2 sat 90
B.E. +3.1
TCO2 26.6
Shifted to MVM 0.50 Pulmonary referral Imp: Pneumonia in the
immunocompromised, T/C COPD, R/O Pulmonary Embolism
Started Acetylcysteine, Ipratropium, Enoxaparin 40mg SQ OD, Doxofylline
S>(0850H) dyspneic O> BP90-100/60-80
on dopamine, HR=105-150, 02sat=84-88%, crackles L>R
MVM shifted to in-line neb 70%
Na 135
K 4.3
Crea 1.7
CXR (4/5) accentuation of pulmonary vasculature consistent with congestion, increase haziness in left base
(1200H)Hydrocortisone 200mg Furosemide 120mg
In-line neb BiPAP intubated
(1305H) sustained V. tach defibrillation 360J x3, amiodarone drip
ABG AC mode 100%
pO2 68.3
pH 7.42
pCO2 37.1
HCO3 23.8
O2 sat 94.2
B.E. -0.2
TCO2 25
ABG O2 at 6LPM
pO2 50.0
pH 7.48
pCO2 36.6
HCO3 26.9
O2 sat 88.1
B.E. +3.7
S> (1600H) drowsy-stuporous
O> BP 88/60, HR=145,
narrow QRS tachycardia at 145bpm
Meropenem started 500mg IV OD
Blood and tracheal aspirate CS
Femoral line inserted, initial cvp=8
Hydrocortisone 50mg IV TID, furosemide 40mg IV TID
S> awake, febrile O> BP 80-120/40-80
on Dopamine, HR=130-140s on Amiodarone drip, Tmax=39.8C 02sat=93-95%
at AC mode 100%
(1705H): unresponsive, GCS=3, pupils anisocoric, BP 70/50, HR=140s, CVP=5-6 norepinephrine drip
Referred to neurology service
Imp: T/C ICH, left with herniation
(2200H): S> comatose O> BP60 palpatory on
Dopamine and Norepinephrine, HR=110s, 02sat=85% at AC mode100%
DNR form signed (2238H): Expired Blood CS: candida
albicans
Cardiopulmonary Arrest secondary to Septic Shock secondary to Severe Pneumonia with Candidemia in an immunocompromised host
Transfusion related acute lung injury Chronic Lymphocytic Leukemia
ELDERLY Patients CLL Patients
Associated co-morbids Age Loss of functional
activity
Mortality: 16-40%
Inherent immune defects
Other complications ie anemia
Immunosuppression Hypercoagulability
Mortality: 40%
Most common cause of invasive fungal infections in humans, producing infections that range from non–life-threatening mucocutaneous disorders to invasive disease that can involve any organ
Clinical Practice Guidelines for the Management of Candidiasis:
2009 Update by the Infectious Diseases Society of America
Broad-spectrum antibacterial agents, use of central venous catheters, receipt of parenteral nutrition, receipt of renal replacement therapy by patients in ICUs, neutropenia, use of implantable prosthetic devices, and receipt of immunosuppressive agents (including glucocorticosteroids, chemotherapeutic agents, and immunomodulators)
Clinical Practice Guidelines for the Management of Candidiasis:
2009 Update by the Infectious Diseases Society of America
Empirical therapy for suspected candidiasis in nonneutropenic patients is similar to that for proven candidiasis
Fluconazole (800-mg [12-mg/kg] loading dose, then 400 mg [6 mg/kg] daily), caspofungin (70-mg loading dose, then 50mg daily), anidulafungin (200-mg loading dose, then 100 mg daily), or micafungin (100 mg daily) is recommended as initial therapy (B-III)
CLL is one of the very few indications for which IVIG has been approved by the FDA
IVIg is a fractionated blood product derived from plasma and primarily contains IgG
It has been postulated that the risk of infection should be reduced by parenteral administration of normal Ig
It is one of the primary means of improving immune function in patients with CLL
In a non randomized study, the majority of patients had significantly lower rates of serious bacterial infections
IVIg was also associated with significant reductions in hospital admissions and febrile episodes
Matutes, E. Management of Infectious Complications in Chronic Lymphocytic Leukemia. Eur J of Clin and Med Onco. (2009)
There is no contraindication for use of either pneumococcal or influenza vaccine on immunocompromised patients
Vaccines that are not composed of live viruses or bacteria are generally safe for administration to immunocompromised persons
Lederman, et al. Immunuzation of the Immunocompromised Host. Clin Focus on Primary Immune Deficiencies.1998.(1):2
However, studies by Morrison stated that immunization responses are suboptimal due to impaired antibody production as well as defects in antigen presentation
Morrison, V. Management of Infectious Complications in Patients with CLL. Am Soc Hema.2007
TRALI is a clinical syndrome that is temporally associated with transfusion of plasma containing blood components, including whole blood, PRBC, platelet, FFP, cryoprecipitate and IVIG.
TRALI, whose incidence maybe 1 in 5000 transfusions has long been recognized as a subtype of ARDS and there is a growing appreciation that TRALI maybe underrecognized and underreported
Zilberberg et al. Critical Care 2007,11:R63
CLASSIC DELAYED
TIME of ONSET Within 2-6hrs 6-72 hours
RATE OF DEVT Rapid Over several hours
SETTING Outside ICU ICU patient
COFACTORS None Sepsis, trauma, burns
PATHOPHYSIO Antineutrophil antibodies
Bioactive mediators
INCIDENCE Relatively uncommon
Common
COURSE Usually resolves in 48-96 hours
Resolves slowly
RESOLUTION Complete May progress to fibroproliferative ARDS
MORTALITY 5-10 35-45
Although the exact mechanism of TRALI is not known, there is increasing evidence that this reaction can be triggered by 2 distinct mechanisms
The first suggests that TRALI is caused by donor antibodies against human neutrophil antigens or human leukocyte antigens in the lungs of the recipient
The second implicates a 2 event model: The first event is an inflammatory condition
of the patient causing sequestration and priming of neutrophils in the pulmonary component
The second event is the transfusion containing either antibodies or bioactive lipids that have accumulated during blood storage stimulating the primed neutrophils to release proteases
The result in both hypothesis is endothelial damage, capillary leak, and extravasation of neutrophils
It has a spectrum of clinical presentation, however, pulmonary symptoms are always present and can range in severity from mild dyspnea to fulminant respiratory distress and pulmonary failure
Pulmonary symptoms may be accompanied by fever, chills, tachycardia, bilateral pulmonary edema, hypoxemia, hypotension.
There is no specific treatment for TRALI
There is no specific treatment for TRALI. It is based on the maintenance of the hemodynamic balance of the patient and on the necessity for the earliest possible application of ventilatory support
Rosalio Torres, MD Tarcela Gler, MD Gregorio Ocampo,
MD Reynato Kasilag,
MD Jose Mari Anson,
MD Carla Chuatico, MD Jesus Relos, MD
Faye Salindong, MD
Mench Echiverri, MD
Christian Estanislao, MD
Paul Quetua, MD 2245 family
Diagnosis often difficult to obtain and is frequently missed
Mortality in untreated PE is approximately 30%, but with adequate (anticoagulant) treatment, this can be reduced to 2–8%.
Common causes of illness and death after surgery, injury, childbirth and in a variety of medical conditions
Nevertheless numerous cases go unrecognized and hence untreated, with serious outcomes
Prevalence of PE at autopsy (approximately 12–15% in hospitalized patients) has not changed over three decades
As modern medicine improves the longevity of patients with malignancy and cardiac and respiratory disease, PE may become an even more common clinical problem
Requires no evidence of disease on physical examination or microscopic examination of blood (ALC < 4000/μL) and bone marrow (< 30% lymphocytes, no nodules) and recovery of hemoglobin, neutrophil and platelet counts
Physical examination Normal Symptoms None Lymphocytes 4x109/L Neutrophils ≤1.5x109/L Platelets > 100x109/L Hemoglobin >11g/dL
(untransfused) Bone marrow < 30%; no nodules lymphocytes