Iron-Deficiency Anemia

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Complete Blood Count
(CBC, Hemogram)
Doç. Dr. Jale Çoban
Klinik Biyokimya Uzmanı
Topics:
1- Blood
2- Blood Cells
3- Complete Blood Count (CBC)
4- CBC Parameters
5- Aim of CBC Testing
BLOOD
As a vital component, blood has 2 phases:
- Cellular phase and
- Liquid phase
All metabolic substances are present homogenously
in this liquid phase.
Whole Blood Centrifuged with Anticoagulant
BLOOD COMPONENTS
• • Plasma (Vs. Serum)
– Proteins
– Lipids
– Carbohydrates
– Ions
– Water
• Cellular
• Erythrocytes
• Leukocytes
• • Polymorphonuclear or granulocytes
• Neutrophil
• Basophil
• Eosinophil
• Monomorphonuclear or agranulocytes
• Monocytes
• Lymphocytes
• Platelates
The hierarchy of haematopoiesis
4
Complete Blood Count Parameters:
Complete Blood Count: Analysis of blood cells
Complete Blood Count: Analysis of blood cells
Complete Blood Count (CBC, Hemogram)
Red blood cells
White blood cells
Platelets
Erythrocyte and indices
Erythrocyte and indices
• RBC –Red blood cell –Number of all erythrocytes
• Hgb – Hemoglobin concentration
• HCT – Hematocrit value: Erythrocyte ratio of
total blood volume
• MCV – Mean erythrocyte volume in total sample
• MCH – Mean hemoglobin volume per RBC
• MCHC – Mean hemoglobin concentration of RBC
• RDW – SD – Calculated distribution width of
erythrocytes, standard deviation
• RDW – CV- Calculated distribution width of
erythrocytes, coefficient of variation
• RET – Reticulocyte count
Erythrocyte = Red Blood Cells = RBC
Erythrocyte = Red Blood Cells = RBC
• Erythrocytes have an oval
shape, biconcava, flattened,
with a depression in the
center.
• This design is optimized for
the exchange of oxygen with
the environment that
surrounds it which gives them
flexibility to pass through the
capillaries, where they release
the load of oxygen.
• The diameter of an
erythrocyte is typically 6-8
micrometers.
Erythrocyte =
Red Blood Cells = RBC
• The half-life of the erythrocyte normal
average is 120 days
• Erythrocyte does not have nucleus
and mitochondria
• Erythrocytes are quantitatively the
most numerous of the blood.
4.5 – 6 millyon cells / uL
Erythrocyte = Red Blood Cells = RBC
• Red blood cells contain hemoglobin, which is
responsible for transporting oxygen and
carbon dioxide. It is also the pigment that
gives red color to blood.
Haemoglobine (Hgb)
Haemoglobine (Hgb) (g/dL)
• Hemoglobin is a protein in red blood cells.
• The main role of hemoglobin is to transport
oxygen from the lungs to tissues, and CO2
from tissues to the lungs, by unstable binding
of oxygen and CO2 with bivalent iron heme.
• Normal results vary, but in general are:
Male: 14 - 18 g/dL
Female: 12 - 16 g/dL
Hemoglobin Ölçümü
• Hemoglobin potasyum ferrisiyanür
“Drabkin Solüsyonu” ile
siyanmethemoglobine dönüştürülmekte
ve hemoglobin yoğunluğu, 540 nm.deki
adsorbansın spektrofotometrik olarak
ölçülmesi ile hesaplanır
Hematocrit (Hct) (%)
• The hematocrit is the
proportion of blood volume
that is occupied by red blood
cells.
• Hct = MCV x RBC
• Referance range:
Man: %40 – 50
Femine: %36 – 45
Hematocrit/Packed Cell Volume
HCT/PCV
6
Erythrocyte indices
(MCV, MCH, MCHC)
• MCV – Mean erythrocyte volume in total sample
• MCH – Mean hemoglobin volume per RBC
• MCHC – Mean hemoglobin concentration of RBC
MCV (Mean Corpuscular Volume)
84-90 fl
• The MCV is expressed in femtoliter(fl)
=(10-15L) and hematology analysers
either directly measure this parameter
Empedans Yöntemi
Kırmızı Küre
Bir Kırmızı Kürenin
İlerleyişi
Algılama Bölgesi
Oscilloscope
Oscilloscope
Trombositlerin Kırmızı Kürelerin
Arasından Seçilmesi
20 fl
2 fl
Ana Hat
Trombositler
Değişik Büyüklükte
Kırmızı Küreler
MCV (Mean Corpuscular Volume)
84-90 fl
• MCV = 84-90 fl
NORMOCYTİC erytrocyte
• MCV = < 80 fl
MİCROCYTİC erythrocyte
• MCV = >90 fl
MACROCYTİC erythrocyte
MCH (Mean Corpuscular Hemoglobin)
(27-35 pg)
• The MCH is expressed in pg/RBC and is
calculated by hematology analyzers
according to the following equation:
Hgb
• MCH (pg) = ------ x 10
RBC
• Hgb = 15g/dl
• RBC = 5x1012/L
• MCH = 15/5 x 10 = 30 pg
MCH (Mean Corpuscular Hemoglobin)
(27-35 pg)
• MCH = 27-35 pg
NORMOCROMİC RBC
• MCH < 27 pg
HİPOCROMİC RBC
• MCH > 35 pg
HİPERCROMİC RBC
MCHC
(Mean Cell Hemoglobin Concentration)
(32-36 g/dl)
• The MCH is expressed in g/dl of red
blood cells and is calculated by
hematology analyzers according to the
following equation:
• MCHC = Hgb / Hct x 100
• MCHC = (Hgb/ (RBC x MCV)) x 1000
• Hgb = 15 g/dL
• Hct = %45
• MCHC = 15 /45 x 100 = 33.3g/dL
RDW (%)
(Red cell distribution width)
eritrositlerin büyüklüklerine göre
dağılım genişliği
• RDW reflects the size distribution of the erythrocyte population
• RDW is a measurement of anisocytosis.
• RDW(%) = MCVsd /MCVmean x 100
• Reference values: %11-15
• RDW normal, MCV decrease = Thalassemia
• RDW increase, MCV decrease = Fe
deficiency
Clinical significance
•
MCV, MCH, MCHC and RDW are
important tools for:
1. The clasification of anemias
2. The early detection of processes that
will cause anemia
3. The investigation of the underlying
etiology of anemias
RETICULOCYTE
• Reticulocyte is the precursor of
mature erytrocytes, before losing the
nucleus.
• Referance range % 0.5 – 1.5
•
Erythocytes (RBC)
Based on the measured RBC count, the
MCV, and Hgb concentration, hematology
analyzers calculate the following
parameters:
1. Hct, also referred to as packed cell volume
2. Mean cell hemoglobin content (MCH)
3. Mean cell hemoglobine concentration
(MCHC).
ANEMİA
decrease in normal number of
red blood cells or less than the
normal quantity of
hemoglobin in the blood.
Male: < 14 g/dL
Female: < 12 g/dL
Classification of Anemia
Based on cell size (MCV)
• Macrocytic (large) MCV >100 fl
(femtoliters)
• Normocytic (normal) MCV 8-99 fl
• Microcytic (small) MCV<80 fl
Based on hemoglobin content (MCH)
• Hypochromic (pale color)
• Normochromic (normal color)
There are several different types of
anemia, each with a specific cause and
treatment, including the following:
•
•
•
•
•
•
•
•
iron-deficiency anemia
megaloblastic (pernicious) anemia
anemia of folate deficiency
hemolytic anemia
sickle cell anemia
thalassemia
aplastic anemia
chronic anemia
Hemolytic Anemia
• Hemolytic anemia is a disorder in which
the red blood cells are destroyed faster
than the bone marrow can produce
them. The term for destruction of red
blood cells is hemolysis.
Hemolytic Anemia
• Intrinsic - the destruction of the red blood
cells due to a defect within the red blood cells
themselves. Intrinsic hemolytic anemias are
often inherited, such as sickle cell anemia and
thalassemia. These conditions produce red
blood cells that do not live as long as normal
red blood cells.
• Extrinsic - red blood cells are produced
healthy but are later destroyed by becoming
trapped in the spleen, destroyed by infection,
or destroyed from drugs that can affect red
blood cells.
Hemolytic Anemia
Iron-Deficiency Anemia
• The most common cause of anemia is iron
deficiency.
• Iron is needed to form hemoglobin.
• Iron is mostly stored in the body in the
hemoglobin.
• About 30 percent of iron is also stored as
ferritin and hemosiderin in the bone marrow,
spleen, and liver.
Iron Deficiency Anemia
Characterized by the production
of small (microcytic)
erythrocytes and a diminished
level of circulating hemoglobin
(Iron-Deficiency Anemia) Occurs If (Iron Intake < Iron Loss)
Causes of Iron-Deficiency Anemia:
1. Inadequate Iron Supply:
Poor nutritional intake
Malabsorption (gastric surgery, achlorhydria, celiac disease, etc.)
Abnormal transferrin function (congenital atransferrinemia,
autoantibodies to transferrin receptors)
2. Increased Iron Requirements
Blood loss
Extensive and prolonged menses
Gastrointestinal disorders (hemorrhoids, peptic ulser, colonic cancer, etc.)
Pulmonary disorders (hemoptysis, pulmonary hemosiderosis)
Urologic disorders (hematuria)
Nasal disorders (nose bleeds)
Chronic blood donations
Dialysis
Hookworm infestation
Intravascular hemolysis with hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
Cardiac valve protheses
Rapid growth (between ages 2 and 36 months, adolesance)
Pregnancy and lactation
Causes of
Iron Deficiency Anemia
•
•
•
•
•
•
Inadequate ingestion
Inadequate absorption
Defects in release from stores
Inadequate utilization
Increased blood loss or excretion
Increased requirement
Stages of Iron Deficiency
• Stage 1: moderate depletion of iron stores;
no dysfunction
• Stage 2: Severe depletion of iron stores; no
dysfunction
• Stage 3: Iron deficiency
• Stage 4: Iron deficiency (dysfunction and
anemia)
Tests for Iron Deficiency
•
Serum iron: poor indicator, highly
variable day to day and during the day
•
Ferritin - most sensitive—chief storage
form of iron; directly proportional to
iron stored in cells
Tests for Iron Deficiency
•
Total iron binding capacity
(TIBC)—capacity of transferrin
to bind iron
•
Transferrin—globulin that
binds/transports Fe from gut
wall to tissues
Percent saturation of
transferrin (calculate by
dividing serum iron by the
TIBC)
TIBC increases in iron
deficiency
•
•
As stored iron falls, saturation of
transferrin decreases
Transferrin Saturasyonu, Total ve Serbest Demir Bağlama
Kapasiteleri Nelerdir ?
Serbest Demir
Bağlama Kapasitesi =
Serbest Transferrin
Serum Demiri = Demir
Bağlamış
Olan Transferrin
Total Demir Bağlama Kapasitesi
= Serum Transferrin Aktivitesi
(~Düzeyi)
Transferrin Saturasyonu = Serum Demiri / Total Demir Bağlama Kapasitesi
Transferrin Saturasyonu = Serum Demiri / (Serum Demiri + Serbest Demir Bağlama Kapasitesi)
CBC in IRON DEFICIENCY ANEMIA
•
•
•
•
•
•
Hb: 10.7 g/dL (female 12-16; male 13.5-17.7) 
MCV: 72 fL (80-100)  = microcytosis
MCH: 26 pg (27.5-33.2)  = hypochromia
RDW: 15 (11.5-13.4)  = anisocytosis
WBC: 4900/L (4 000-11 000) N
Platelet count: 450 000/L (150 000-450 000) N
PERIPHERAL SMEAR in IDA
SERUM IRON PARAMETERS
in IDA
Iron: 5 g/dL (60-150) 
TIBC (transferrin level): 467 g/dL (250-435) 
Transferrin saturation: % 7 (15-45) 
Ferritin:2 ng/mL (15-200) 
Transferrin receptor level 
Iron-Deficiency Anemia
Iron-deficiency anemia
Iron-deficiency anemia
Thalassemia
• Normal hemoglobin, also called hemoglobin A.
• HbA has four protein chains—two alpha globin and
two beta globin.
• The two major types of thalassemia, alpha and beta,
are named after defects in these protein chains.
Thalassemia
• Thalassemia is an inherited blood disease. Inherited" means
they're passed on from parents to children through genes.
• The genetic defect results in reduced rate of synthesis of one of
the globin chains that make up hemoglobin.
• People who have thalassemias can have mild or severe anemia.
• This condition is caused by a lower than normal number of red
blood cells or not enough hemoglobin in the red blood cells.
Thalassemia
Iron-deficiency
Thalassemia
ANEMİA
MCV
Decreased
Microcyter
Anemia
1.
Iron-deficiency
NORMAL
Normocrom
Normocyter
Anemia
1. Hemolytic Anemia
2.Chronic disease
2.Chronic disease
3.Thalassemia
3. Haemoragy
increased
Macrocyter
Anemia
Megaloblastik
1. B12-Folat def.
2. Drogs
3. Herediter
Classification of anemias, dependent on
the RDW and MCV
• Microcytic isocytic (β thalassemia minor)
Decreased MCV
Normal RDW
• Microcytic anisocytic ( Iron deficiency anemia)
Decreased MCV
Increased RDW
• Normocytic Isocytic ( Chronic disease anemia)
Normal MCV
Normal RDW
• Macrocytic Isocytic (Pernicious anemia)
Increased MCV
Increased RDW
Microcytic anisocytic
(Iron deficiency anemia)
Microcytic isocytic
(β thalassemia minor)
Decreased MCV
Increased RDW
Decreased MCV
Normal RDW
MİKROSİTER ANEMİLERDE AYIRICI TANI
FAKTÖR
IronDeficiency
Anemia
TALASEMİ
MİNÖR
cronic
diesises
Anemia
MCV
decreased
decreased
decreased
Normal
RDW
increased
Normal
Normal
Serum Fe
decreased
Normal
decreased
TDBK
increased
Normal
decreased
Ferritin
decreased
Normal
decreased
Normal
increased
Megaloblastic Anemias
• A form of anemia characterized by the
presence of large, immature, abnormal red
blood cell progenitors in the bone marrow
• 95% of cases are attributable to folic acid or
vitamin B12 deficiency
Pernicious Anemia
A macrocytic, megaloblastic anemia caused by
a deficiency of vitamin B12.
• Usually secondary to lack of intrinsic factor
(IF)
• May be caused by strict vegan diet
• Also can be caused by ↓gastric acid secretion,
gastric atrophy, H-pylori, gastrectomy,
disorders of the small intestine (celiac
disease, regional enteritis, resections), drugs
that inhibit B12 absorption including
neomycin, alcohol, colchicine, metformin,
pancreatic disease
Megaloblastic
(pernicious) anemia
Iron defitions
Sideroblastic Anemia
• Microcytic, hypochromic form
• Inherited defect of heme synthesis
enzyme
• High serum and tissue iron levels
Complete Blood Count
(CBC, Hemogram)
Granulopoiesis
11
12
Lymphopoiesis
13
WHİTE BLOOD CELLS
• WBC – Number of all leucocytes
• NEUT# and % - Neutrophil count and percent
• LYMPH# and % - Lymphocyt count and percent
• MONO# and % - Monocyt count and percent
• EO# and % - Eosanophil
• Baso# and % - Basophil count and percent
Complete Blood Count Parameters
LEUKOCYTES
(granulocytes, lymphocytes, and monocytes)
1. Polymorph nucleated cells
(multiple nucleated)
2. Mononuclear cells:
(one nucleus)
lymphocyt
monocyt
LEUKOCYTES referance range
Neutrophils
% 50 – 70
1.5–8 x103
Lymphocytes
% 20 – 40
0.6-5 x103
Monocytes
%2–9
0.1-0.8 x103
Eosinophils
%2–4
0.7 x103
Basophils
%<1
0.1 x103
Complete Blood Count Parameters:
WBC disorders
• Leukocytosis : non-neoplastic causes of
elevated white cell counts (-philias”):
•
•
•
•
•
Granulocytosis (neutophilia)
Eosinophilia
Lymphocytosis
Monocytosis
Basophilia
• Leukopenia : decreased production “-penias”
•
•
•
•
Neutropenia
Lymphocytopenia
Thrombocytopenia
Pancytopenia
– Drugs, viral infections, Radiation, chemotherapy
etc.
A high number of WBCs is called
LEUKOCYTOSİS
It may be due to:
• Infectious diseases
• Inflammatory disease (such as
rheumatoid arthritis or allergy)
• Leukemia
• Severe emotional or physical stress
A low number of WBCs is called
LEUKOPENİA
It may be due to:
• Bone marrow failure (for example, due to
infection, tumor, or abnormal scarring)
• Collagen-vascular diseases
• Disease of the liver or spleen
• Radiation therapy
Complete Blood Count Parameters:
Neutrophils(%40-74)
Most frequent cell in peripheral blood.
They have phagocytic functions.
They play roles in acute and bacterial
infections.
Lymphocyte (%19-48)
Most important cell in immun system.
Second most frequent cell in peripheral
blood.(adult)
Most frequent cell before 3 years of age.
Plays role in viral and chronic infections.
T cells helps to activate or inhibit the other
cells and act cytotoxic.
B cells are secreting antibodies.
MONOCYTES (%2-9)
• After leaving the bone marrow, monocytes remain in
the bloodstream about 7 days, then move into
tissues, where they become macrophages.
• Monocytes phagocytize bacteria and larger
particles
• they contain great quantities of lipase and can thus
degrade bacteria with lipidic capsule, such as
tuberculosis
• Monocytes have a dominant role in immunity because
they present the ingested antigen on their surface so
that it can be recognized by lymphocytes.
Complete Blood Count Parameters:
Monosit(%2-9)
The biggest cell in peripheral blood.
Precursor of macrophages.
has phagocytic activity.
Eosinophil (%0-6)
Especially important in
allergic diseases
and
paracytic infections.
Complete Blood Count Parameters:
Basophils (%0-1.5)
Especially important in storage of
biologic amines (Histamin etc.)
Immunglobulins are attached to this
cells.
Basophils (%0-1.5)
• Basophils appear in many specific kinds of inflammatory
reactions, particularly those that cause allergic
symptoms.
• When activated, basophils degranulate to release
histamine, proteoglycans (e.g. heparin and chondroitin),
and proteolytic enzymes (e.g. elastase and
lysophospholipase).
• Each of these substances contributes to inflammation.
Complete Blood Count Parameters:
Platelets (150-450.000/uL)
• They have no
nucleus.
• They play role in
clotting (adhesion,
aggregation and
secretion)
17
Thrombocytopenia
• Decreased
Production:
– Diffuse marrow
disease:
• aplasia,
• leukemia,
– Impaired thrombocyte
production:
• alcohol,
• drugs,
• HIV
– Ineffective production:
• megaloblastic anemia.
• Decreased Survival:
– Immune
• Idiopathic
thrombocytopenia,
• SLE,
• Iso-immune,
• drugs,
• HIV
– Non-Immune
• DIC,
• Thrombocytic
thrombocytopenic purpura
• Sequestration
– Hypersplenism.
• Dilutional
– Massive transfusion.
Definitions:
Erythrocyte
Leucocyte
Platelets
Neutrophil
Lymphocyte
Monocyte
Eosinophil
Basophil
Increase
Polycytemia(*)
Erythrocytosis
Leucocytosis
Thrombocytosis
Neutrophilia
Lymphocytosis
Monocytosis
Eosinophilia
Basophilia
Decrease
Anemia
Leucopenia
Thrombopenia
Neutropenia
Lymphopenia
-
Sedimentation Rate
(Erythrocyte Sedimentation Rate or
ESR)
• sedimentation rate is the rate at
which red blood cells precipitate in a
period of 1 hour
• It is a common hematology test which
is a non-specific measure of
inflammation.
What is the normal sedimentation
rate?
• The normal sedimentation rate (Westergren
method) for
males is < 15 millimeters per hour,
females is < 20 millimeters per hour.
• The sedimentation rate can be slightly more
elevated in the elderly.
C-reaktive protein (CRP)
• C-reactive protein is an acute phase
protein that is produced by the liver
during an inflammatory reaction
Clinical significance
• An increased plasma concentration of
CRP is an important indicator of:
- Acute or chronic inflammation such as
may accompany bacterial infection
- Autoimmune or immune complex
disease
- Tissue necrosis and malignancy
?
?
?
Iron-deficiency anemia
Aim of Complete Blood Count Testing:
1- Bone marrow dysfunctions (Malignancies,
therapeutic drugs, toxic substances etc.)
2- Anemia and related red blood cell diseases
3- Polystemia and related red blood cell diseases
4- White blood cells and related diseases (Leukemia,
infections, drugs, immunological diseases)
5- Platelets and related diseases
(GIS bleeding, thrombosis, purpura, ITP, massive
transfusion, HSM )
?
?
Anemia (Bleeding)
Polisitemia
?
POLİSİTEMİ VERA
1 YILDAN BERİ GİDEREKL ARTAN BAŞAĞRISI TANIMLIYOR.
MM
Thalasemi taşıyıcı
Analiz Yöntemleri (1)
• Empedans yöntemi: Hücreler dar bir
aralıktan geçerlerken doğru akımda
meydana getirdikleri empedans (elektrik
direnci) değişimi ile sayı ve büyüklükleri
belirlenir. Voltaj değişiklikleri hücre
büyüklüğü ile doğru orantılıdır.
Analiz Yöntemleri (2)
• Optik sistem: Hücrelerin üzerine gelen
lazer ışını değişik yönlere yansır. Dar açı
ile meydana gelen yansımalar hücre
büyüklüğü, geniş açı ile ortaya çıkanlar
ise hücre yapısının (granularite ve
çekirdek yapısı) belirlenmesinde
kullanılırlar.
Optik Sistem
Hücre Büyüklüğüne Göre
Sinyal Oluşumu
Hücreleri Büyüklüklerine Göre Tanımlanma
Eşikleri
Lökosit Formülü
Çalışma Basamakları
• Kan örneğini özel antikoagülanlı tüpden aspire
edilir
• Bir kısmındaki kan lizise uğratılır Hgb ve BK
analizi yapılır.
• Kalan kısım ise hemolize uğratılmadan kırmızı
küre ve trombosit analizi için kullanılır.
Analiz Öncesi Dönem
Kanın alınmasındaki hastanın fizyolojik durumundan
alınan kan örneğinin laboratuvara ulaşıp OTKSC’de
analiz edilinceye kadar geçen dönemi içine almaktadır.
•Fizyolojik (yaş, yükseklik, gebelik, sigara)
•Örnek alınması (bekleme süresi, antikoagülanların
etkileri ve endojen interferans)
•EDTA’ya bağlı psödotrombositopeni
•Trombosit satellitizmi
EDTA’ya Bağlı Trombosit Kümelenmesi (Yalancı
Trombositopeni)
Trombosit Satellitizmi
(Yalancı Trombositopeni)
Ölçüm
Hatalı Yüksek
Beyaz Küre Kriyoproteinler
Heparin
Paraproteinler
Çekirdekli Eritrositler*
Trombosit Kümeleşmesi
Kırmızı
Kriyoproteinler
Küre
Dev trombositler
Hgb
Htk
Karboksihemoglobin>%10
Kriyoproteinler
İn vivo hemoliz
Heparin
BKS> 50x10e9/L
Hiperbilirubinemi
Lipemi
Paraproteinemi
Kriyoproteinler
Dev trombositler
BKS> 50x10e9/L
Hiperglisemi (>600mg/dl)
Hatalı Düşük
Pıhtılaşma
Ezilmiş hücreler (basket
hücreleri)
Üremi
İmmun baskılayıcı ilaçlar
Otoagglutinasyon
Pıhtılaşma
İn vitro hemoliz
Pıhtılaşma
Sulfhemoglobinemi (?)
Otoagglutinasyon
In vitro hemoliz
Mikrositer kırmızı
Ölçüm
(MCV)
(MCHC)
Trombosit
Sayımı
Hatalı Yüksek
Otoagglütinasyon
BKS> 50x10e9/L
Hiperglisemi
Kırmızı küre
deformabilitesinde azalma
Otoagglütinasyon
Pıhtılaşma
In vitro hemoliz
Hatalı yüksek hemoglobin
ölçümü
Hatalı düşük hematokrit
ölçümü
Kriyoproteinler
Hemoliz
Mikrositer kırmızı küre
Kırmızı kürelerde
inklüzyon cisimcikleri
Beyaz kürelerde
fragmentasyon
Hatalı Düşük
Kriyoproteinler
Dev trombositler
İn vitro hemoliz
Mikrositer kırmızı küre
Şişmiş kırmızı küre
BKS> 50x10e9/L
Hatalı düşük hemoglobin
ölçümü
Hatalı yüksek hematokrit
ölçümü
Pıhtılaşma
Dev trombositler
Heparin
Trombosit kümeleşmesi
“clumping”
Trombosit satellitizmi
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