PATIENT MANAGEMENTPATIENT MANAGEMENT

PANCYTOPENIA

25 Feb 2015Sirirat Assawalerknun

HISTORYHISTORY เด็กหญิงไทยอายุ 11 ป no underlying disease

ิ ํ ศ ีสภูมิลําเนา จ.ศรีสะเกษ

อาการสาํคญั: สงตัวจากรพ.รัฐบาลมารักษาตอดวยเรื่องซีดและ ญ ฐ

เกร็ดเลือดต่ํา

HISTORYHISTORY ประวตัปิจจบุนั

3 ื ี ื ี ศี ี ้ํ ื ึ้3 เดือนกอน มีอาการหนามืด เวียนศีรษะ มีจุดจําเลือดขึน

ตามตัว ไมมีถายดําหรืออาเจียนเปนเลือด ปฎิเสธประวัติไข ไอฎ

น้ํามูก หรือการเจ็บปวยกอนหนานี้

ไป admit รพ.ใกลบาน

HISTORYHISTORYInvestigation:

1 CBC : Hct 19% WBC 4 100 /mm3 (N14% L81%)1. CBC : Hct 19%, WBC 4,100 /mm3 (N14%,L81%),

ANC 574 /mm3 , Platelet 10,000 /mm3

2. DAT : neg, IAT : neg

3 LDH 1673. LDH : 167

4. BMA : dilute marrow, not seen blast cell

HISTORYHISTORYManagement:

LPB 6 unit LPB 6 unit

Platelet concentrate 40 unit

F/U CBC (กอน D/C)

CBC H t 23 5% WBC 2 700 / 3 ( N9% L87%)CBC : Hct 23.5%, WBC 2,700 /mm3 ( N9%,L87%),

ANC 243 /mm3 ,Platelet 68,000 /mm3

Imp : Pancytopenia

Refer to siriraj hospital

HISTORYHISTORY ประวัติอดีต : ปฎิเสธการเจ็บปวยรุนแรงกอนหนานี้

ประวัติคลอด : ครบกําหนด ไมมีภาวะแทรกซอนหลังคลอด ประวตคลอด : ครบกาหนด ไมมภาวะแทรกซอนหลงคลอด

ประวัติครอบครัว : บิดาเปนพาหะธาลัสซีเมีย

ประวัติวัคซีน : ครบตามเกณฑ

ประวัติยา : ไมไดใชยาใดเปนประจํา

PHYSICAL EXAMINATION (siriraj)PHYSICAL EXAMINATION (siriraj)

V/S : BT 36.5 o C, RR 22 /min, HR 102 /min, BP 108/73 mmHg ,

BW 34.5 Kg (P50), Lt 149 cm (P50-75) g ( ) ( )

GA : alert, markly pale, no jaundice, generalized petechiae,

no ecchymosis, no lymphadenopathy, no rash, no oral ulcer

RS : clear, equal both

CVS : normal S1S2, SEM gr II/VI at LUPSB

Abd : soft no palpable mass no hepatosplenomegalyAbd : soft, no palpable mass, no hepatosplenomegaly

NS : E4V5M6, pupil 3 mm BRTL, motor power Gr V/V all

PROBLEM LISTPROBLEM LIST

Pancytopenia

SEM gr II/VI at LUPSB SEM gr II/VI at LUPSB

INVESTIGATIONINVESTIGATION

CBC

Hb 9.9 g/dl

Hct 28.9%

MCV 79 fl

WBC 2,930 /mm3

N 8.3 %

L 88.7%

ANC 243 /mm3ANC 243 /mm

Plt 22,000 /mm3

Reti 0 2%Reti 0.2%

PANCYTOPENIA

PANCYTOPENIAPANCYTOPENIA

Definition

Hemoglobin (Hb) < 10 g/dl

Absolute neutrophil count < 1.5 x109/l

Pl t l t t < 100 109/l Platelet count < 100 x109/l

Pancytopenia in children, Pak J Med Sci 2013 Vol. 29 No. 5

Manual of Pediatric Hematology and Oncology Fifth Edition

Journal, Indian Academy of Clinical Medicine, 2012; Vol13 No. 4

ETIOLOGYETIOLOGY

Indian Journal of Pathology and Microbiology - 54(1)76,January-March 2011

Aplastic anemiaAplastic anemia

Acute leukemia

Bone marrow

Megaloblastic anemiaMegaloblastic anemia

Hypersegmentalneutrophil

Peripheral Blood smearneutrophil

Gaucher's Disease

Storage diseaseStorage disease

Niemann–Pick disease

Granuloma

PANCYTOPENIAPANCYTOPENIA

Anemia : pallor, weakness, loss of appetite

Leukopenia : increased susceptibility to infections

Thrombocytopenia : petechiae, easy bruising,

severe nosebleeds and bleeding into GI andsevere nosebleeds and bleeding into GI and

renal tracts

SYMPTOMS AND SIGNSSYMPTOMS AND SIGNS

Indian Journal of Pathology and Microbiology - 54(1)76,January-March 2011

INVESTIGATION OF PANCYTOPENIAINVESTIGATION OF PANCYTOPENIA

Laboratory CBC CBC

Reticulocyte count

Peripheral blood smear

Bone marrow exam (aspiration/biopsy)

INVESTIGATION OF PANCYTOPENIAINVESTIGATION OF PANCYTOPENIA

Further LaboratoryA t i ANA DNA tit DAT Autoimmune : ANA , DNA titer, DAT

Infection : Viral serology eg. HIV, EBV, parvovirus, hepatitis profile,

PCR for virus

Nutritional def : Serum vitamin B12, serum folate levels

X-Rays: Bone, chest etc / ultrasound abdomen

Other biopsies : Lymph node Other biopsies : Lymph node

Fanconi anemia : Chromosome breakage

IN THIS PATIENTIN THIS PATIENT

BM biopsy

♧ d h ll l i (20 25% f l )♧ moderate hypocellularity (20-25% of total marrow)

♧ marked decrease in megakaryocytesg y y

♧ predominance of erythroid precursors with maturation

♧ decrease in myeloid precursors

♧ ti f t d l♧ negative for tumor and granuloma

DIAGNOSISDIAGNOSIS

Severe aplastic anemiaCriteriaAt least 2 of following peripheral blood findings: Reticulocytes <1%, corrected for hematocrity %, Absolute neutrophil count < 0.5×109/L Platelets < 20×109/L Platelets < 20×10 /LAND

BM biopsy with < 25% normal cellularity OR BM biopsy with < 25% normal cellularity OR BM biopsy with <50% normal cellularity in which less

th 30% f ll h t i tithan 30% of cells are hematopoietic

MANAGEMENTMANAGEMENTOF PANCYTOPENIAOF PANCYTOPENIA

MANAGEMENTMANAGEMENT

Supportive treatment Specific treamentp

SUPPORTIVE RXSUPPORTIVE RX

Anemia : blood transfusion Neutropenia :p

♤ Prophylaxis ATB♤ Treament of Febrile neutropenia♤ Treament of Febrile neutropenia♤ Granulocyte concentrates

Thrombocytopenia/Bleeding : ♤ Platelet concentrates

Hygiene

TransfusionTransfusion

Transfusions Only when indicated Side effects:

- Iron overload - HLA alloimmunization, - Infection transmission (eg : HIV,HCV,HBV,CMV)

TransfusionTransfusion

Irradiation ….. Leukocyte reduced blood (LRB) …..y ( )

TransfusionTransfusion

Irradiation of blood products

♧ To prevent transfusion associated GvHD (TA GvHD)♧ To prevent transfusion-associated GvHD (TA-GvHD)

♧ To reduce sensitization to HLA and non-HLA antigens

from multiple transfusions in patients who are candidates

f t l t d f ATG t t tfor transplant and for ATG treatment

Irradiation of blood productsIrradiation of blood products

I f t 6 th f Infants < 6 months of age All pediatric malignancies

I i l h f i Intrauterine or neonatal exchange transfusions Recipients of components from blood relatives and all designated

donorsdonors Recipients of crossmatched or HLA matched platelets Myelosuppressive therapy (chemotherapy or irradiation) Myelosuppressive therapy (chemotherapy or irradiation) Patients undergoing, or candidates for, marrow or peripheral blood

progenitor cell transplant H Congenital immunodeficiencyprogenitor cell transplant H. Congenital immunodeficiency syndromes, include suspected DiGeorge Syndrome

PEDIATRIC TRANSFUSION GUIDELINES (Approved by Medical Staff Executive Committee on 12/11/2006)

Leukocyte reduced bloodLeukocyte reduced blood

Leukocyte reduced blood (LRB) - leukocyte-poor packed red cell, LP-PRC

: < 5 x 108 WBC/bag- leukocyte-depleted packed red cell, LD-PRC

: < 5 x 106 WBC/baga) pre-storage filtration ) p gb) bedside filtration

Leukodepleted blood componentsLeukodepleted blood components

Recommended♣ Prevent of FNHTRs (Febrile non haemolytic transfusion reactions)♣ Reducing graft rejection after haemopoietic cell transplantation.♣ Prevention of transmission of CMV infections.♣ Fetal/Neonatal transfusions.

Possible♠ Prevention of refractoriness to platelet transfusion♠ Kidney transplants.♠ Immunomodulation.

Recommendations for the transfusion of red blood cells 2009; 7: 49-64

ANEMIAANEMIA

Recommendations for the transfusion of red blood cells 2009; 7: 49-64

Blood TransfusionBlood Transfusion

A safe haemoglobin level ≥ 8 g/dl,

Based on symptoms and co-morbidities; quality of life.

Patients with cardiac pulmonary vascular co morbidities Patients with cardiac, pulmonary, vascular co-morbidities

may require a higher transfusion.

Regular blood transfusion is associated with risk of

alloimmunization and iron overload.

Blood TransfusionBlood Transfusion

Dose ….

Premedication ….

Blood TransfusionBlood Transfusion

Dosage :

10 cc/kg will increase hemoglobin 2.5-3.0 g/dl.10 cc/kg will increase hemoglobin 2.5 3.0 g/dl.

Transfusion time:

In uncomplicated patients infuse over 2-3 hours.

HCC syndrome (hypertension convulsion cerebral y ( yp

hemorrhage syndrome)

Blood TransfusionBlood Transfusion

ผูปวยที่มีปญหาการทํางานของหัวใจ และระดับ pretransfusion Hb < 5 g/dL

1. ใหปริมาตร PRC ที่ใหเทากับขนาด 2 เทาของระดับ Hb แตไมเกิน 5 mL/kg

2. อัตราการให < 2 mL/kg /ชั่วโมง โดยใหปริมาณนอย แตบอยครั้ง (ทุก 24–48 ชม.)

3. พิจารณาใหยาขับปสสาวะกอนให PRC

ผที่มีปร วัติ febrile non hemol tic transf sion reaction (FNHTR) ให ผูทมประวต febrile non-hemolytic transfusion reaction (FNHTR) ให

Chlorpheniramine และ Paracetamol รับประทานกอนใหเลือด 1/2-1 ชม.

ถามีอาการ FNHTR ขณะใหเลอืดใหหยุดการใหเลอืดทันที และวัด vital signs

Platelet TransfusionPatients Recommendation

Platelet Transfusion

Leukemia/Lymphoma

<10x109/L for clinically stable patients receiving CMT<40x109/L with signs of bleeding, high fever, critically ill

hyperleucocytosis rapid fall in platelet count APL hyperleucocytosis, rapid fall in platelet count, APL, coagulation abnormality (*)

Post stem cellt l t ti

<10x109/L hi h l l i f ti t b (*)transplantation higher level : require for patient as above (*)higher level : Patients undergoing invasive procedures

Solid tumors <10x109/L higher level : require for patient as above (*)higher level : Patients undergoing invasive procedureshigher level : for patients with bladder tumors or necrotic tumors

Chronicthromboctyopenia

Stable patients with chronic, stable, severe thrombocytopeniadue to alloimmunization should be observedPlatelet transfusions with clinically significant bleeding only.

Guideline for Platelet Transfusion Thresholds for Pediatric Hematology/Oncology Patients 2011

Platelet TransfusionPatients Recommendation

Platelet Transfusion

Lumbarpuncture

<20x109/L<50x109/L : recommend for diagnostic LP for newly diagnosed patients with leukemia to minimize risk of traumatic LPpatients with leukemia to minimize risk of traumatic LP.higher level : require for patient as above (*)

Majori i

<40-50 x109/L hi h l l i f ti t b (*)invasive

procedurehigher level : require for patient as above (*)

Guideline for Platelet Transfusion Thresholds for Pediatric Hematology/Oncology Patients 2011

NeutropeniaNeutropenia

Prophylaxis ATB Treament of Febrile neutropenia Treament of Febrile neutropenia Granulocyte concentrates

ATB ProphylaxisATB Prophylaxis

Prophylactic antibiotic and antifungal drugs should

be given to patients with ANC <0 5X109/lbe given to patients with ANC <0.5X109/l.

ATB ProphylaxisATB Prophylaxis

ATB ProphylaxisATB Prophylaxis

Prophylactic antibiotics prevent Gram-negative sepsis, ♧ combination of two non-absorbable antibiotics:

neomycin and colistin♧ quinolone : ciprofloxacinq p

Concern about emergence of ♧ quinolone resistant bacteria♧ quinolone resistant bacteria, ♧ increase in Gram-positive infections♧ increase risk of Clostridium difficile♧ increase risk of Clostridium difficile

Ciprofloxacin cannot be used to treat febrile neutropenia if it is used prophylactically

Antifungal ProphylaxisAntifungal Prophylaxis

Aplastic anaemia are high risk of fungal infection, including Aspergillus.

Fluconazole: no cover against Aspergillus species. Drugs of choice are itraconazole and posaconazole.g p No data to justify use of voriconazole for prophylaxis

Febrile neutropeniaFebrile neutropenia

Febrile neutropeniaFebrile neutropenia

Fever with neutropenia is an indication for hospitalization.

Diagnosis : physical exam, H/C and cultures from other sites, CXRg p y , ,

Start treatment without waiting for culture results.

Persisting fever or previous or suspected fungal infection Persisting fever or previous or suspected fungal infection

- Diagnostic procedures for invasive fungal infections :

galactomannan and CT chest should be performed.

Systemic antifungal therapy concern early in therapy of fever in

neutropenic AA patients.

Febrile neutropeniaFebrile neutropenia

Antibiotics :

♤ synergistic combination such as aminoglycoside and♤ synergistic combination such as aminoglycoside and

b-lactam penicillin

♤ depending on local hospital microbiological sensitivity/

resistance patternsresistance patterns.

G-CSFG CSF

C id d f i i f i h Considered for severe systemic infections that are not responding to intravenous ATB and anti-fungal drugs

Short course of subcutaneous G-CSF : dose of 5 mcg/kg per day

Discontinued after 1 week if there is no increase in neutrophil counts

Granulocyte transfusionsGranulocyte transfusions

Considere in life-threatening neutropenic sepsis. Adverse events

# febrile reactions, # HLA alloimmunization # transfusion-related acute lung injury (TRALI)

Supportive careSupportive careS i l N t i di t h Special Neutropenic diet such as: (1) washing hands before preparing food, (2) storing raw meat fish chicken in a way that avoids(2) storing raw meat, fish, chicken in a way that avoids

contamination of other food, (3) washing in hot water dishes and cutlery that contact raw meat

before placing them in contact with other food,(4) using fresh food without any mold, (5) consumption of Pasteurized juices and dairy products, (6) avoiding uncooked meats, seafood, eggs and unwashed fruits

and vegetablesand vegetables (7) avoiding raw nuts and dried fruits due to the risk of fungal spores.

Supportive careSupportive care

Hand washing and rubbing with alcohol-based disinfection

must be used before and after handling the patient by

staff and by visitors.

HygieneHygiene

oral hygiene :- soft toothbrushes to avoid bleeding, lesions of mucosa- Regular mouth care: antiseptic mouthwash

ActivitiesActivities

Early mobilization to avoid bed sores and guarantee

good pulmonary functiongood pulmonary function.

Physical exercises are recommended if the patient is

well enough.

Passive mobilization and breathing may be helpful for Passive mobilization and breathing may be helpful for

hospitalized patients who are not able to perform such

physical activities.

Psychological supportPsychological support

support of patients and families

age appropriate explanation of disease treatment and age-appropriate explanation of disease, treatment, and

prognosis are important at diagnosis and during course

of disease

improve therapy adherence and disease outcomes improve therapy adherence and disease outcomes.

SPECIFIC RXSPECIFIC RX

Depend on underlying diseases Severe aplastic anemiap

- HLA-identical sibling BMT- Immunosuppressive therapy: pp py

antithymocyte globulin (ATG) and ciclosporin

การพยาบาลผปวยที่มีภาวการพยาบาลผูปวยทมภาวะ THROMBOCYTOPENIATHROMBOCYTOPENIA

THANK YOUTHANK YOU