kul kel hematologi sem v

8/13/2019 Kul Kel Hematologi Sem V

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KELAINANPADAHEMATOLOGI

Indriani Silvia

Patologi Klinik

FK UNSWAGATI


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THEREDBLOODCELL

Transports oxygen, called oxyhemoglobin, when itgives up its oxygen it is deoxyhemoglobin.

Also binds and transports carbon dioxide,

carbaminohemoglobin.

Makes up 97 % of RBC250 million Hbmolecules per RBC

Men: 14-18 mg/dl blood

Women: 12-16 mg/dl blood


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THEREDBLOODCELL

Types of Hemoglobin (Hb)

Hb A

96% of adult Hb (2 2)

Hb A2 3% of adult Hb (2 2)

Hb F

1 % of adult Hb (2 2)


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THEREDBLOODCELL


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HEMATOPOIESIS


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THEREDBLOODCELL


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REVIEWREDBLOODCELLDISORDERS

MARROWPRODUCTION


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THEREDBLOODCELL


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TYPES OF FORMED ELEMENTS IN THE

BLOOD


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WHATISHEMATOLOGY?

Livercontains phagocytic cells known

as Kupffer cells that act as a filter for

damaged or aged cells in a manner

similar to, but less efficient than thephagocytic cells in the spleen.

If the bone marrow cannot keep up with the

physiologic demand for blood cells, the liver

may resume the production of blood cells thatit began during fetal life


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SUMMARYOFBLOODFORMINGORGANS


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TRANSFUSIONTHERAPY

Bloodgroup

Antigen Antibody Donor to Recipientfrom

A A Anti-B A A, O

B B Anti-A B B, O

AB AB Neither AB A, B, AB, O

O Neither Anti-A/Anti-B

O, A, B, AB O

Universal donor "O"Universal recipient "AB"


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ADVERSETRANSFUSIONREACTIONS

Acute Hemolytic ReactionSymptoms

Fever, chills and fever, the feeling of heat alongthe vein in which the blood is being transfused

Pain in the lumbar region Constricting pain in the chest, tachycardia, hypo-

tension

Hemoglobinemia with subsequent hemoglo-binuria and hyperbilirubin-emia. "feeling of impending doom"


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Acute Hemolytic Reaction

Causes

Human error!

Transfused red cells react with circulating antibody in therecipient with resultant intravascular hemolysis


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Acute Hemolytic Reaction

Frequency

Rare

Prevention

Proper identification of patients, pretransfusion

blood samples and blood components at the

time of transfusion


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Delayed Hemolytic ReactionFalling hematocrit

due to extravascular destruction of thetransfused red blood cells)

Positive direct antiglobulin (Coombs) test(DAT)

Occurs about 4-8 days after blood

transfusion

Patients may manifest fever andleukocytosis Appearing to have an occult infection.


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Febrile Transfusion Reaction

Fever or chill fever

temperature rise of 1.5 F or 1.0 C from the

baselineCytokines and antibodies to leukocyte

antigens reacting with leukocytes or

leukocyte fragments

1 in 8 transfusions


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Allergic urticaria

Laryngeal edema and bronchospasm

1% of recipients

If coupled with another sign, such as fever,evaluation for a hemolytic reaction may be

indicated.


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Allergic Anaphylaxis

Anaphylactic or anaphylactoid

Respiratory involvement with dyspnea or stridor

Cardiovascular instability

hypotension, tachycardia, loss of consciousness,

cardiac arrhythmia, shock and cardiac arrest


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Volume Overload

Transfusion-related volume overload

Infuse smaller volumes more slowly


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Bacterial Contamination

Hypotension, shock, fever and chills,

nausea and vomiting, and respiratory

distressGram stain and blood culture


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IF A TRANSFUSION REACTION IS

SUSPECTED

Follow protocol for transfusion reactions implemented

by the institution


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SUSPECTED

Stopthe transfusion immediately!

Disconnect the intravenous linefrom the

needle.

Seek medical attentionimmediately. If thepatient is suffering cardiopulmonary

collapse, and medical attention is notimmediately available, press for Code"


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SUSPECTED

Checkto ensure that the patient name and

registration number on the blood bag label

exactly with information on the patient's

identification

Do not discard the unit of bloodthat has

been discontinued because it may be

necessary for the investigation of the

transfusion reaction.


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TREATMENTFORTRANSFUSIONREACTIONS

Reaction Type Treatment - Adult Pediatric Follow-up

Acute

Hemolytic

Reactions

Diuretic therapy:Initially, give 40-80

mg Furosemide (Lasix)

intravenously. This dose can be

repeated once. Lack of response

to furosemide in 2-3 hours

indicates the presence of acute

renal failure.

Pediatric dose: 1-2

mg/kg/dose.

May repeat once

at 2-4 mg/kg.

Treat shock and disseminated

intravascular coagulation with

appropriate measures if and when

they appear.

Water loading:The patient should be

hydrated to maintain urinary

output of at least 100 mL/hr until

urine is free of hemoglobin.

Infuse a loading dose of 0.9% sodium

chloride or 5% dextrose in 0.45%

sodium chloride. Chart hourly

urine output. Maintain the urine

output by administeringintravenous fluid at 100 mL/hour

until the urine is free of

hemoglobin. If the patient's

urinary output does not increase,

with this hydration any additional

fluids should be infused with

caution.

Pediatric patients

should receive a

smaller loading

volume of fluid

in proportion to

their body

surface area.


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TREATMENTFORTRANSFUSION

REACTIONS

Delayed

Hemolytic

Transfusion

Reactions

Specific treatment generally is not

necessary

Supplemental transfusion of blood lacking

the antigen corresponding to the

offending antibody may be necessary

to compensate for the transfused

cells that have been removed fromthe circulation.



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REACTIONS


Allergic

Transfusion

Reactions

Antihistamines(e.g., Benadryl). Give

50-100 mg orally or intravenously. If

urticaria develops slowly,

antihistamines may be given orally.

Pediatric dose: 1-2

mg/kg

intramuscularly or

intravenously for 25-

50 mg per average

dose.

Routine use of Benadryl as premedication

for all transfusions, regardless of a history

of allergic reactions, is discouraged.

Aminophyllinefor wheezing, at a dose

of 125-250 mg intravenously slowly

over a period of about five minutes

Pediatric dose: 3

mg/kg/dose in

intravenous drip over

of 20 minutes.

Epinephrinefor severe, acute reactions

including laryngeal edema or

bronchospasm Give 0.1-0.5 mg (0.1-0.5

mL of a 1:1000 solution)

subcutaneously. Subcutaneous dose

may be repeated at 10-15 minute

intervals. The total subcutaneous dose

in a 24-hour period, with rare

exception, should not exceed 5 mg.

Pediatric dose: 0.03

mL/M2 (0.03 mg/M2

of a 1:1000 solution)

given subcutaneously.

A single pediatric

dose should not

exceed 0.3 mg.


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REACTIONS

Febrile

Transfusion

Reactions

Premedicatethe patient with

acetaminophen or other

antipyretic agents when previous

reactions have been extremely

bothersome. Pediatric dose: 10

mg/kg to a maximum of 600 mg.

Aspirin will adversely affect the patient's

platelet function, so non-aspirin

antipyretic agents are preferable.

Severe shaking

Chills

(rigors) can be controlled by the

sedative effect of Benadryl or

Demerol (25-50 mg given

intramuscularly or intravenously

Note: Demerol may cause acute

respiratory arrest. An opiate

antagonist (Narcan) should be

immediately available.

Sepsis Due to

Bacterial

Contaminationof Donor Blood

Treatment of septic shock includes:

terminating the suspected

transfusion immediately, cardio-vascular and respiratory support,

blood culture of the patient, and

administration of broad spectrum

antibiotics including anti-

pseudomonas coverage if the

blood component involved is Red

Blood Cells.



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ANEMIA

Abnormally low number of RBC or Hb levels

Reduced oxygen carrying capacity

Causes

Blood loss

Increased rate of red cell destruction

Hemolytic anemia

Deficient or impaired red cell production


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ANEMIA

Risk factors

Poor diet

Intestinal disorders

MenstruationPregnancy

Chronic conditions

Family history


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ANEMIA

NOT A DISEASE but a symptom

Dependent on severity, speed of development,

age, health status and compensatory

mechanisms

Associated with impaired O2 transport, alteration

in RBC structure or with chronic illness

Not expressed until 50% of RBC mass is lost


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ANEMIA

Signs and symptomsThe main symptom of most types of anemia

is fatigue Weakness

Pale skin Tachycardia

Shortness of breath

Chest pain

Dizziness Cognitive problems

Numbness or coldness in your extremities

Headache


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ANEMIA

Iron Deficiency AnemiaMost common form of anemia

Affects about one in five women

Half of pregnant women and 3 percent of men in

the United States.The cause is a shortage of the element iron

Nutritional imbalance

Slow, chronic bleeding disorders

Inability to recycle plasma iron


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ANEMIA

Vitamin Deficiency Anemias

Folate and vitamin B-12 deficiency

Intestinal disorder that affects the absorption

of nutrientsFall into a group of anemias called

megaloblastic anemias, in which the bonemarrow produces large, abnormal red blood

cells.


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ANEMIA

Anemia of Chronic Disease

Interfere with the production of red bloodcells, resulting in chronic anemia

Kidney failure also can be a cause ofanemia The kidneys produce a hormone called

erythropoietin, which stimulates your bonemarrow to produce red blood cells.A shortage of erythropoietin, which can result from

kidney failure or be a side effect of chemotherapy, canresult in a shortage of red blood cells.


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ANEMIA

Aplastic Anemia

Life-threatening anemia caused by adecrease in the bone marrow's ability toproduce all three types of blood cells redblood cells, white blood cells and platelets

Cause of aplastic anemia is unknown autoimmune disease

Chemotherapy Radiation therapy

Environmental toxins


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ANEMIA

Anemias associated with bone marrowdisease

Leukemia and myelodysplasia, can causeanemia by affecting blood production in thebone marrow

Effects vary from a mild alteration in bloodproduction to a complete, life-threateningshutdown of the blood-making process Myelodysplasia is a pre-leukemic

condition that can cause anemia.Other cancers of the blood or bone marrow,

such as multiple myeloma, myeloproliferativedisorders or lymphoma, can cause anemia.


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ANEMIA

Hemolytic Anemias

Red blood cells are destroyed faster thanbone marrow can replace them.

Autoimmune disorders can produceantibodies to red blood cells, destroyingthem prematurely Hemolytic anemias may cause yellowing of the

skin (jaundice) and an enlarged spleen.


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ANEMIA

Hereditary Spherocytosis

Mutations in the ankyrin molecule with a

secondary deficiency of spectrin along the

cell membrane Reduced red cell stability

Does not affect oxygen carrying capacity

Splenic sequestration


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ANEMIA

Sickle cell anemiaDefective form of hemoglobin that forces red

blood cells to assume an abnormal crescent(sickle) shape.

Mutation for the gene coding for the -globulinchainValine is substituted for glutamic acid HbS

Red cells die prematurely, resulting in achronic shortage of red blood cells. Block blood flow through small blood vessels in

the body, producing other, often painful,symptoms.


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SICKLECELLANEMIA

Single base pair mutation results in a single amino

acid change.

Under low oxygen, Hgb becomes insoluble forming

long polymers

This leads to membrane changes (sickling) and

vasoocclusion


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REDBLOODCELLSFROMSICKLECELLANEMIA

OXY-STATE DEOXY-STATE

Deoxygenation of SS erythrocytes leads tointracellular hemoglobin polymerization, loss ofdeformability and changes in cell morphology.


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ANEMIA

- Thalassemia

Common in Asians

Deletion of glubulin chain loci

4 possible degrees of thalassemia: Silent carrier, loss of a single globulin gene

thalassemia trait, loss of a pair of globulin gene

HbH disease, only a single gene is present

Hydrops fetalis, deletion of all globulin


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THALASSEMIAS

The only treatments are stem cell transplant and

simple transfusion.

Chelation therapy to avoid iron overload has to be

started early.

TALASSEMIA


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POLYCYTHEMIAVERA

An acquired disorder of the bone marrow

that causes the overproduction of all three

blood cell lines

white blood cells, red blood cells, and platelets It is a rare disease that occurs more

frequently in men than women, and rarely in

patients under 40 years old.

causes is unknown


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POLYCYTHEMIAVERA

Usually develops slowly, and most patients

are asymtomatic

abnormal bone marrow cells proliferate

uncontrollably leading to acute myelogenous

leukemia

Patients have an increased tendency to

form blood clots that can result in strokes or

heart attacks Some patients may experience abnormal

bleeding because their platelets are abnormal


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POLYCYTHEMIAVERA

SymptomsHeadache

Dizziness

PruritusFullness in the left upper abdomen

Erythema (face)

Shortness of breath

Orthopnea

Symptoms of phlebitis


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WHITEBLOODCELLS

Collectively known as White Blood Cells(WBC)

Formed elements of the blood with

organelles and a nucleus but lackhemoglobin

Protect the body against microorganisms

and remove dead cells and debris from thebody


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WHITEBLOODCELLS


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WHITEBLOODCELLS

Per l blood Per l of blood

Total WBC count 5,000 10,000

Neutrophils 50 - 70% 2,000 7,000

Lymphocytes 20 - 40% 1,000

4,000Monocytes 1 6% 50 600

Eosinophils 1 5% 50 500

Basophils 0 2% 0 - 100


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WBC DISORDERS

Leukopenia

Decreased peripheral white cell count due to

decrease numbers of any specific types of

leukocytes

Leukocytosis

Nonneoplastic elevation of WBC count


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WBC DISORDERS

Neutropenia

Reduction in the number of granulocytes

(


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WBC DISORDERS

Neutropenia

Decreased or defective granulopoiesis

Aplastic anemia

Anti-neoplastic agents Other drugs: chloramphenicol, sulfonamides,

chlorpromazine

Accelerated removal or destruction

Aggressive and chronic infections


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WBC DISORDERS

Manifestation of Neutropenia

Infections

Signs and Symptoms

Malaise, chills, fever

Ulcerative necrotizing lesions of the mouth,

skin vagina and GI tract


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WBC DISORDERS

Reactive Leukocytosis

Increase number of WBC

Common reaction due to a variety of

inflammatory states caused by microbial ornon-microbial stimuli

Usually non-specific


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WBC DISORDERS

Causes of Leukocytosis

Polymorphonuclear leukocytosis Acute bacterial infections

Eosinophilic leukocytosis Allergic disorders

Monocytosis Chronic infections

Lymphocytosis Chronic immunologic disease

NONMALIGNANT LEUKOCYTE


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NONMALIGNANT LEUKOCYTE

DISORDERS

Leukemoid reactionthis is an extreme neutrophilia with aWBC count > 30 x 109/L

Many bands, metamyelocytes, and myelocytes are seen

Occasional promyelocytes and myeloblasts may be seen.

This condition resembles a chronic myelocytic leukemia(CML), but can be differentiated from CML based on thefact that in leukemoid reactions:

There is no Philadelphia chromosome

The condition is transient

There is an increased leukocyte alkaline phosphatasescore(more on this later)

Leukemoid reactions may be seen in tuberculosis,chronic infections, malignant tumors, etc.


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LEUKEMOID REACTION

N P W


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NEOPLASTICPROLIFERATIONOFWHITE

CELLS

1. Leukemianeoiplasms of the

hematopoietic stem cells

2. Malignant lymphomascohesive tumor

lesions; neoplastic lymphocytes3. Plasma cell dyscrasiasarising from the

bones; localized disseminated

proliferation of antibody forming cells

4. Histocytosesproliferative lesions of

histiocytes

N P W


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CELLS

Leukemia

Malignant neoplasm of the hematopietic

stem cells

BM replaced by unregulated, proliferating,immature neoplastic cellsblood

leukemiaenter spleen, lymph nodes

Most common cancer in the paediatric age

Leading cause of death in children between

3 and 14 years old

N P W


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CELLS

Classification of LeukemiaA. According to cell type and state of cell

maturity Lymphocyticimmature lymphocytes and

their progenators

Myelocyticpluripotent myeloid stem cellsand interferes with maturation of allgranulocytes, RBC and platelets

B. Acute or Chronic Acuteimmature cells (blast)

Chronicwell differentiated leukocytes

N O S C P O O O W


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CELLS

LEUCOCYTES BENIGN DISORDERS


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QUALITATIVECHANGES(MORPHOLOGY)

Congenital Pelger-Huet anomaly

Bilobed and occasional unsegmented neutrophils

Autosomal recessive disorder



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UCOC S G SO S

QUALITATIVECHANGES(MORPHOLOGY) CONTD.

Neutrophil hyper-segmentation Rare autosomal dominant condition

Neutrophil function is essentially normal

May-Hegglin anomaly

Neutrophils contain basophilic inclusions of RNA

Occasionally there is associated leucopenia

Thrombocytopenia and giant platelet are frequent



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Alders anomaly Granulocytes, monocytes and lymphocytes contain granules which stain

purple with Romanowsky stain

Granules contain mucopolysaccharides



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Chediak-Higashi syndromeAutosomal recessive disorder

Giant granules in granulocytes, monocytes and lymphocytes

Partial occulocutaneous albinism

Depressed migration and degranulationRecurrent pyogenic infections

Lymphoproliferative syndrome may develop

Treatment is BMT



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Acquired Toxic granulation

Dohle bodies

Pelger cells

Hypersegmented neutrophils



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QUALITATIVECHANGES(FUNCTIONAL)

Leucocyte adhesion deficiency Chronic granulomatous disease

Chediak-Higashi syndrome

Primary immunodeficiency

Severe combined immunodeficiency Common variable immunodeficiency

Isolated IgA deficiency

T-cell immunodeficiency

Thymic aplasia (Di George syndrome)


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ACUTELEUKEMIA(CELLKINETICSTUDIES)

Block in the differentiation of leukemic cellswith prolonged genration time clonal

expansion of the transformed stem cells +

failure of maturation accumulation of

leukemic blastsuppress normal

hematopoietic stem cells


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ACUTELEUKEMIA

Features

Sudden onset (3 months)

Depressed marrow function

Bone pain and tendernessGeneralized lymphadenophaty

Splenomegaly, hepatomegaly

CNS: headache, vomiting


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ACUTELYMPHOCYTICLEUKEMIA(ALL)

Most common leukemia in children (80%)

Treatable and potentially curable

Classified according to lymphocytes and

state of maturation1. Early B cell

2. Pre-B cell

3. Mature B cell

4. Early T cell

5. Mature T cell


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ACUTEMYLEOCYTICLEUKEMIA(AML)

Acute Non-lymphocytic Leukemia (ANLL)

Most common in adults; >50% 60years old

70% of adults will enter remission with

induction chemo 25-35% of those in remission will have a 5 year

survival rate

BM transplant


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ACUTEMYLEOCYTICLEUKEMIA(AML)

Treatment

Selective radiation

Chemotherapy

1. Induction2. Intensification

3. Maintenance and consolidation

Bone marrow transplant


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CHRONICLEUKEMIA

Insidious onset

Incidental findings during routine exam


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CHRONICLYMPHOCYTICLEUKEMIA

Proliferation and accumulation of maturelymphocytes which are immunologically

incompetent

B cell line (US)

T cell line (Asia)

Hairy cell leukemia


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CHRONICMYELOCYTICLEUKEMIA

15% of all leukemias

Chromosomal abnormality (Ph1)

Mostly B cell disease

Leukocytosis Splenomegaly

Hepatomegaly

Lympadenopathy

Bone marrow transplant 5 year survival

for 50-75% of patients


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CHRONICMYELOCYTICLEUKEMIA

Two distinct phases

Chronic

Last about 3-4 years

Near endaccelerated phase: fever, nightsweats, malaise

Acute

2-4 months

Poor prognosis, palliative management


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MALIGNANTLYMPHOMAS

Primary solid tumors of the lymphoid system

Cancers involving lymphocytes during

maturation or storage in the bone marrow

Third most common malignacy in children


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MALIGNANTLYMPHOMAS

Hodgkins Lymphoma

Disorders primarily involving the lymphoid

tissues

Anatomical spreadMorphological presence of Reed-Sternberg

cells

60-90% cure rate


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MALIGNANTLYMPHOMAS

Manifestations of Hodgkins

A symptoms

Painless progressive enlargement of a single or

group of nodes (neck)

May spread continuously through out the

lymphatic system

B symptoms

Fever, night sweat, weight loss Fatigue, anemia


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MALIGNANTLYMPHOMAS

Treatment for Hodgkins

Radiation

Chemotherapy


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MALIGNANTLYMPHOMAS

Non-Hodgkins Lymphoma

Involves lymphoid tissue and may spread to

various tissues

Mostly B cell (80%)Cause may be viral or genetic

EBV

Immunosuppresed patients

AIDS

After organ transplant


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MALIGNANTLYMPHOMAS

Treatment

Early stageradiation

Late stagechemo and radiation

BM transplant


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CONCLUSIONS

Transfuse for any severe anemia with physiologiccompromise.

Decide early whether transfusion will be rare or part

of therapy.

Avoid long-term complications by working with yourblood bank and using chelation theraoy.


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SCHISTOCYTES


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BURRCELLS

SPUR CELLS


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SPURCELLS

TARGETCELLS


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HYPOCHROMIC MICROCYTIC ANEMIA


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HYPOCHROMICMICROCYTICANEMIA


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SPHEROCYTES


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TEARDROPCELLS


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