Lymphadenopathy

& Splenomegaly

Prof Dr Nayera Hazaa

 ILOs
• Distinguish between infectious and noninfectious causes of
lymphadenopathy and splenomegaly in children.
• Describe an approach for lymphadenopathy and splenomegaly
diagnosis
• Name and classify pathogens that cause lymphadenopathy and
splenomegaly in children.
Lymphatic
system
Age 3 months Age 12 months
=6 cm =7 cm

Age 6 years Age 12 years

=9.5 cm = 11.5 cm

Age >15 years

= 12cm for girls
13cm for boys
Lymphadenopathy
Classification
• Enlargement of ≥ 2 non-
contagious lymph nodes groups
Generalized

Enlargement of a single lymph

Regional or localized node or multiple contagious
nodal regions.
 Suspicious Lymphadenopathy
Axillary/inguinal/cervical Presence of
glands which are >2cms, symptoms
Posterior auricular,
discreet, firm and non- suggestive of
epitrochlear or
tender, and do not get
supraclavicular LND are systemic diseases (
smaller after 2 week’s
abnormal arthritis, skin rash,
treatment with
antibiotics weight loss……)

Mediastinal adenopathy Generalized more likely

is frequently malignant malignant (except EBV)
Causes of lymphadenopathy
 Causes of
Splenomegaly

Infection Space Immune Hematologic Storage

occupying Malignancy Liver
dysregulation disorders disease diseases
lesions

Hemangioma SLE Portal Gaucher

Viral Hamartoma Hemolytic
JRA anemias leukemia hyperten Neimann
Bacterial Cysts sion pick
some HLH Lymphoma
Fungal PID MPS
LCH
Parasitic
ALPS
Infectious causes
 Viral Infection

EBV
CMV
Tonsillopharyngitis, HSV
Fever, malaise, fatigue,
splenomegaly (>50%), occasional
Grouped vesicles
fever, malaise, fatigue, gingivostomatitis
hepatosplenomegaly
periorbital edema

HIV
Rubella
Recurrent bacterial infection,
Maculopapular rash with
opportunistic infection, fever,
cranial to caudal
diarrhea, encephalopathy,
progression, cough, coryza,
poor weight gain,
conjunctivitis, Koplik spots
hepatosplenomegaly
 Bacterial /spirochetal Infection

Brucellosis
Group A streptococcal
disease Fever, sweats, malaise, fatigue,
weight loss, ingestion of
Rash followed by unpasteurized milk; exposure to
desquamation cattle, sheep, or goats

Syphilis
Rash, fever, malaise,
anorexia, and weight loss
hepatomegaly
 Parasitic Infection
Toxoplasmosis Leishmaniasis
in immunocompetent hosts Cutaneous lesions,
asymptomatic; myalgia, fatigue, fever, organomegaly, fever,
splenomegaly, and maculopapular rash cachexia; exposure to
exposure to cats sandflies

Malaria
Fever, travel to or residence
in an endemic area
Non-infectious causes
 Immunological causes
Vasculitis syndromes
(systemic lupus • Patients may have generalized adenopathy
erythematosus, rheumatoid during the acute phase of illness
arthritis)

Chronic granulomatous • Recurrent infection, skin abscesses,

disease suppurative adenitis

Serum sickness • Rash, splenomegaly, myalgia, arthritis

 Metabolic/Miscellaneous causes

Gaucher •Hepatosplenomegaly, anemia,thrombocytopenia,

disease osteopenia. Neurological and skeletal affection

Niemann-Pick •Hepatosplenomegaly, loss of neurologic function

disease

Sarcoidosis •Multisystem granulomatous disease; generalized

adenopathy with prominent cervical involvement
Gaucher disease Niemann-Pick disease
 Metabolic/Miscellaneous causes

Langerhans cell •Rash (brown to purplish papules), mucosal

lesions, lytic bone lesions, proptosis, diabetes
histiocytosis insipidus

Hemophagocytic • Fever, hepatosplenomegaly, neurologic symptoms, rash

lymphohistiocytosis

Drugs
Phenytoin, phenobarbital, • Severe maculopapular rash, fever, hepatosplenomegaly,
carbamazepine, isoniazid, aspirin, jaundice, anemia, leukopenia.
barbiturates, penicillin, tetracycline,
iodides, sulfonamides……..
Langerhans cell
histiocytosis
 Kawasaki disease
The diagnosis of KD requires the presence of fever lasting at least 5 days*
without any other explanation combined with at least 4 of the 5 following criteria.
A significant proportion of children with KD have a concurrent infection;
therefore, ascribing the fever to such an infection or to KD requires clinical
judgment.

Bilateral bulbar conjunctival injection

Oral mucous membrane changes, including injected or fissured lips, injected

pharynx, or strawberry tongue

Peripheral extremity changes, including erythema of palms or soles, edema of

hands or feet (acute phase), and periungual desquamation (convalescent phase)

Polymorphous rash

Cervical lymphadenopathy (at least 1 lymph node >1.5 cm in diameter)

 Approach to a child with
lymphadenopathy & splenomegaly
 Focused History /complaint
Cough: Pneumonia (bacterial, viral, fungal)
Local history of Sore throat: GAS, adenovirus, diphtheria
Constitutional symptoms (fever weight loss, night
infection sweats)

• Horner syndrome (miosis, ptosis, anhidrosis) or

Miscellenous opsoclonus myoclonus
• Immunization status /Drug intake

• Unpasteurized animal milk

• Animals
Contact • Undercooked meats
• Travel to endemic areas
 Focused History /complaint

Bone marrow • Rash (purpura,petichea/echymosis/ bleeding)

• Pallor
infiltration • Infection

Abdominal • Hepatomegaly /splenomegaly or both

• Masses( Lymphadenopathies)
enlargement • Jaundice

• Generalized or localized lymphadenopathies

Swellings (cervical, axillary, inguinal )
• Bone swellings
 Focused History /complaint
Hematological malignancy

Mediastinal Abdominal Generalized

syndrome lymph nodes oedema
Dyspnea/orthopnea Compression on Malignant
biliary duct-→ effusions and
Dysphagia jaundice
Oedema of the face
ascites
/upper extremities Intussusception
Myeloid sarcoma

Mediastinal mass
Focused History /complaint

Bone -
FUO aches

Loss of
weight
 Focused History /complaint

Arthritis Autoimmune hemolytic

Pain /red/swelling/ loss of anemia ( jaundice /change in
function color of urine )
Diagnosis
 Investigations

LDH
CBC Serology for CMV and EBV
Leucopenia/leucocytosis Serology for other illnesses Portal venous doppler
Thrombocytopenia as warranted by the history Abdominal Us/ CT
and examination
Anemia
Chest radiograph

Lymph nodes biopsy

Immunoglobulins /Collagen
Supraclavicular nodes Bone marrow
vascular disease
Massively enlarged nodes ( >4 cm ) examination/flowcytometry
Tests(ESR,C3,C4,ANA,ADNA)
Group of nodes with a total diameter
>3 cm
Blood transfusion
 ILOs

• Distinguish between different blood products.

• Describe indications of different blood products
• Classify different transfusion reactions .
 Blood Products

Red cell Platelet

concentrate Plasma concentrates

Plasma derivative
■ Albumin
■ Coagulation factor Cryoprecipitate
concentrates
■ Immunoglobulins
 Blood donation selection criteria
WHO, Guidelines on Assessing Donor Suitability for Blood Donation, 2012

❑ 18-65 years
❑ Donors of whole blood donations should weigh at least 45 kg to donate 350 ml
Age/weight ± 10% and 50 kg to donate 450 ml ± 10%

❑Female donors during menstruation can donate, defer pregnant female till
6 months after delivery and lactating female.
Gender ❑Maximizing the collection and production of plasma and platelet
concentrates from male donors.
❑Screening multiparous female donors for HLA and/or HNA antibodies.

Good ❑No malnutrition or any debilitating condition with sound mental status
❑Look for signs of injecting drug use, tattooing , body piercing.
health/Hb ❑Haemoglobin level of not less than 12.0 g/dl for females and not less than
% 13.0 g/dl for males as the threshold.
Whole blood unit

450 ml whole blood donation (510 ml total volume)

contains:
■ 450 ml donor blood
■ 63 ml anticoagulant-preservative solution
■ Haemoglobin approximately 12 g/ml
■ Haematocrit 35%–45%
■ No functional platelets
■ No labile coagulation factors (V and VIII)
Infection risk
Routine screening for transfusion-transmissible infections, including HIV-1 and HIV-2,
hepatitis B and C, other hepatitis viruses, syphilis, malaria and Chagas disease
Storage
■ Between +2°C and +6°C in approved blood bank refrigerator, fitted with a temperature
chart and alarm
■ During storage at +2°C and +6°C, changes in composition occur resulting from red cell
metabolism
■ Transfusion should be started within 30 minutes of removal from refrigerator
Indications
■ Red cell replacement in acute blood loss with hypovolaemia
■ Exchange transfusion
■ Patients needing red cell transfusions where red cell concentrates, or suspensions are not available

Contraindications
Risk of volume overload in patients with:
■ Chronic anaemia
■ Incipient cardiac failure

Administration
■ Must be ABO and RhD compatible with the recipient
■ Never add medication to a unit of blood
■ Complete transfusion within 4 hours of commencement
RED CELL CONCENTRATE
(‘Packed red cells)

150–200 ml red cells without plasma

Haemoglobin approximately 20 g/100 ml
Haematocrit 55%–75%

Every 1 ml/kg of packed cells should

increase the hematocrit by at least 1% in
pediatric patients, and 1 unit will
increase Hb at least 1 gm %
Indications
■ Replacement of red cells in anaemic patients thalassemia patients with a hemoglobin level less than 9.0
gm/dl

■ Use with crystalloid replacement fluids or colloid solution in acute blood loss

■when the hemoglobin level is less than 13.0 gm/dl and one of the following documented conditions exist:

severe pulmonary disease ,cyanotic heart disease ,heart failure

■ to suppress endogenous hemoglobin production in patients with diagnosed sickle-cell disease when one of
the following conditions exist:

documented cerebrovascular accident

documented acute chest syndrome

documented splenic and/or hepatic sequestration

documented recurrent priapism

 PLATELET CONCENTRATES
one unit in a volume of 50–60 ml of plasma should contain:
■ At least 55 x 109 platelets
■ <1.2 x 109 red cells
■ <0.12 x 109 leucocytes
Pooled unit: platelets prepared from 4 to 6 donor units ‘pooled’ into one pack to contain an adult
dose of at least 240 x 109 platelets
Single donor unit: platelets prepared from one donation by apheresis Platelet content 150–500 x
109
1 unit of platelet concentrate/10 kg body weight will cause an increment of 50,000 at 10-60 min
Indications
■ the platelet count is equal to or less than 10,000/µl and less than 20,000/µl if feverish
■ the platelet count is equal to or less than 50,000/µl and the recipient is scheduled for a
minor procedure within 12 hours or there is active bleeding. And if less than 100,000/µl in
case of major procedure.
■ a qualitative platelet dysfunction is documented with active bleeding.

Not indicated in:

— Idiopathic autoimmune thrombocytopenic purpura (ITP)
— Thrombotic thrombocytopenic purpura (TTP)
— Untreated disseminated intravascular
 Plasma
Pack containing the plasma separated from one whole blood donation within 6 hours of
collection and then rapidly frozen to –25°C or colder for up to 1 year. Volume of pack is
200–300 ml
■ Contains normal plasma levels of stable clotting factors, albumin and immunoglobulin
■ Factor VIII level at least 70% of normal fresh plasma level
Dosage
Initial dose of 15 ml/kg
Administration
Before use, should be thawed in the blood bank in water basin which is between 30°C to
37°C. Higher temperatures will destroy clotting factors and proteins
Indications
■ Replacement of multiple coagulation factor deficiencies: e.g.
— Liver disease
— Warfarin (anticoagulant) overdose
— Documented blood coagulation factor deficiency (Factors II, V, VII, IX X,
or XI) and a suitable factor concentrate is not available.
■ Disseminated intravascular coagulation (DIC)
 Prepared from a single unit of FFP by slowly
thawing the FFP at 4°C and then harvesting
the precipitant by centrifugation

Each unit of cryoprecipitate (volume = 10 - 25 ml/bag) contains

100 - 120 IU of factor VIII, 100 - 250 mg of fibrinogen, 40 - 70%
Cryoprecipitate of the original amount,VIII:vWF (von Willebrands factor) and 20 -
30% of the original amount of factor XIII

Cryoprecipitate should preferably be ABO/Rh

compatible, but it does not have to be cross-
matched
Indications
➢Von Willebrand's disease (type II and type III)
➢Hemophilia A if factor VIII replacement concentrates are not available
➢Hypofibrinogenemia (serum fibrinogen < 100mg/dl)
➢Dysfibrinogenemia
➢Tansfusion-induced hypofibrinogenemia + active microvascular bleeding
➢DIC-induced hypo/dysfibrinogenemia + active microvascular bleeding
LEUCOCYTE-DEPLETED RED CELLS

A red cell suspension or concentrate containing <5 x 10 6 white cells per pack, prepared by
filtration through a leucocyte-depleting filter

Leucocyte depletion significantly reduces the risk of transmission of cytomegalovirus (CMV)

A leucocyte filter may also be used at the time of transfusion

Indications
■ Minimizes white cell immunization in patients receiving repeated transfusions
■ Reduces risk of CMV transmission in special situations
■ Patients who have experienced two or more previous febrile reactions to red cell
transfusion
 Irradiation of blood components
Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion
task force. British Journal of Haematology. 2010; 152, 35–51

The minimum dose achieved in the

irradiated volume should be 25 Gy, All donations from first- or second-
with no part receiving more than degree relatives (1B) should be
50 Gy (1B). irradiated (2C).

Red cells may be irradiated at any time up
to 14 d after collection, should be
transfused within 24 h of irradiation (1A).
Platelets can be irradiated at any stage
during storage and can thereafter be
stored up to their normal shelf life (1A).
Irradiation is indicated for all severe T
lymphocyte immunodeficiency syndromes (
1A), Hodgkin lymphoma ( 1B), recipients of
allogeneic HSCT till 6 months post-
transplant ( 1B), autologous HSCT till 3
months post-transplant
Transfusion
reactions
 Transfusion reactions: prevention, diagnosis, and treatment. Delaney etal the lancet.2016 ;38
American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327-355.
ACUTE HAEMOLYTIC TRANSFUSION DELAYED HEMOLYTIC
REACTIONS TRANSFUSION REACTIONS
Sudden onset of fever or chills, loin pain , 24 h to 28 days after transfusion, dark urine or
hypotension, and dyspnoea, haemoglobinuria or jaundice (45–50%) followed by fever; chest,
haemoglobinaemia, DIC, acute renal failure, shock. abdominal or back pain

Diagnosis is based on the clinical findings and A fall or failure of haemoglobin increment, rise in
demonstration of serological incompatibility. indirect bilirubin, or a positive direct
antiglobulin (Coombs’) test

Additional transfusions to maintain desired Hb. Red

blood cell exchange transfusion
Management is supportive. methylprednisolone proposed for management of
DHTR in SCD patients

Prevention relies on systems-based practices and

comprehensive training to ensure proper patient Prospective extended red cell antigen matching ( 1A).
identification at critical steps in the specimen collection
and transfusion processes (grade 1A)
 Transfusion reactions: prevention, diagnosis, and treatment. Delaney etal the lancet.2016 ;38
Febrile non-haemolytic reactions
Temperature rise of 1°C or higher, and can
be accompanied by transient hypertension,
chills rigors, and discomfort.
A diagnosis of. exclusion
Antipyretic drugs and
pethidine
Pre-storage leucocyte reduction can prevent
FNHTR (1A).
Premedication with antipyretics does not
decrease rate of reactions and should be
discouraged (1A)
Septic transfusion reactions
During or within 4 h of transfusion. No
improvement after cessation of transfusion or
antipyretics or the presence of other clinical signs
Bacterial cultures should be taken from the
patient and any indwelling lines before
antibiotics.
Broad-spectrum antibiotics as β-lactams and
aminoglycosides started empirically with
anti-Pseudomonas coverage if a red blood
cell unit is implicated (1A)
Donor screening and proper skin disinfection
before collection, sequestering the first 10–50 mL
of donated blood that is diverted away from the
collected blood, and pre-transfusion bacterial
surveillance of platelet units (1B)
 Allergic / anaphylaxis
Transfusion reactions: prevention, diagnosis, and treatment. Delaney etal the lancet.2016;38

There is no evidence to support

During or within 4 h of transfusion
rash, pruritus, urticaria and
localized angio-oedema. severe
reactions ( anaphylaxis) with
bronchospasm, respiratory distress,
and hypotension.
In mild/ moderate allergic routine prophylaxis with
antihistamines or glucocorticoids in
transfusion reactions
case of previous mild allergic
(cutaneous symptoms only), H₁
antihistamine administration is transfusion reactions ( 2C).
given (1A). premedication with antihistamines
only in case of previous moderate to
severe reaction ( 2C)

Anaphylactic reactions require

prompt intramuscular
administration of epinephrine (1A).
2nd line drugs: H₁ antihistamine Minimization of the plasma
(1C), bronchodilators ( 1C); content of the unit
glucocorticoid for intravenous
administration (1C); intravenous H₂
antihistamine (1C).
 Transfusion reactions: prevention, diagnosis, and treatment. Delaney etal the lancet.2016;38

Transfusion-associated circulatory Transfusion-related acute lung injury

overload
New onset(within 4-6 h of transfusion), or exacerbation of
three or more of the following, : respiratory distress,
increased central venous pressure, left heart failure,
positive fluid balance, or pulmonary oedema
( NHSN- SHOTS )
Within 6 h (up to 72h after transfusion) with dyspnoea,
tachypnoea, and hypoxaemia, sometimes accompanied by
rigors, tahycardia, fever, hypothermia, and hypotension or
hypertension. Leucopenia, bilateral interstitial infiltrates
on chest radiograph

Treatment of transfusion-associated circulatory over-load Management of transfusion-related acute lung injury is

requires stopping transfusion and administering supportive, with supplemental oxygen as needed, and the
supplemental application of restrictive tidal volume ventilation and a
oxygen. Administration of diuretics can restrictive fluid strategy ( 1A).
be both diagnostic and therapeutic(2C)
At-risk patients should be identified (2C) and given The use of male donors only for plasma and plasma used
transfusions slowly over 3–4 h (2C), with the smallest for suspension of buffy coat derived platelet pools, and
quantity of blood products given to achieve the clinical goal screening of female apheresis platelet donors for HLA/HNA
(2C). antibodies with retesting after pregnancies(2C).
Thank you