Kelainan Trombosit

dr.Besly Sinuhaji, MSc,Sp.PK

Trombosit
 Hematopoietic Cell Differentiation
CFU-L pluripotential blast colony-forming cell self renew

lymphocyte

CFU-GEMM self renew

BFU-E CFU-GM CFU-Eo CFU-Bas CFU-Meg

CFU-E CFU-G CFU-M

erythrocyte neutrophil monocyte eosinophil basophil megakaryocyte

 Thrombopoiesis
Bone Marrow
Precursors Proliferating Endoreduplicating Blood Tissue

CFU-Meg 1N 2N 8N 32N

Megakaryoblast
Megakaryocyte
CFU-GEMM
Platelets
Circulating
and
Marginating
 Trombosit/Platelet/Keping Darah

Megakaryoblast Megakaryocytes Platelets

 Trombosit adalah sel darah tak berinti

yang diproduksi dari sitoplasma
megakariosit
 diameter 2-3 μm
 sel yang aktif sec metabolik, berinteraksi
dg.lingk.
 inisiasi hemostasis
 Trombosit

 Trombosit mengandung 2 granula spesifik :

1. Granula alfa ( - granules):
- fibrinogen (merup mediator agregasi trombosit dg
perantara reseptor GpIIb/IIIa)
- fibronectin
- faktor V dan VIII
- Platetet factor 4 (PF4)
- Platelet-derived growth factor (PDGF)
- Transforming growth factor  (TGF- )

2. Granula delta (dense-bodies) -  granules:

- adenine nucleotides (ADP & ATP)
- kalsium (Ca)
- histamin
- serotonin
- epinefrin
 Aktivasi trombosit

1. Adesi trombosit
2. Reaksi pelepasan
3. Agegasi trombosit
4. Reaksi pelepasan
5. Pembentukan sumbat trombosit
 Aktivasi trombosit
1. Adesi trombosit
• merupakan perlekatan antara trombosit dg kolagen yg terpapar
• dimediasi oleh von Willebrand factor (VWF) sebagai jembatan antara
reseptor GpIb dg kolagen yg terpapar

2. Reaksi pelepasan (release reaction)

• Sekresi isi granula trombosit segera setelah adesi
• Sekresi: ADP (agregasi tr), sintesis thromboxan
A2 (TXA2), Ca (koagulasi)

3. Agregasi trombosit
• Tjd setelah adesi & sekresi
• ADP & TXA2 merup agonis (agregator)
• Trombosit saling beragregasi, & mensekresi ADP & sintesis TXA2
dst
• Tjd amplifikasi agregasi tr
• Hasil dr aktivasi tr : ekpresi kompleks fosfolipid di permukaan
Ca binding site & koagulasi intrinsik
2

Trombosit berperan penting pada hemostasis yaitu

pembentukan dan stabilisasi sumbat trombosit.
Pembentukan sumbat trombosit terjadi melalui beberapa
tahap yaitu adhesi trombosit, agregasi trombosit dan
reaksi pelepasan.
Lapisan Endotel Rusak Jaringan ikat sub-endotel terbuka

Adhesi trombosit

Agregasi trombosit

Reaksi pelepasan

ADP, ATP, Ca, serotonin, epinefrin, nor-

epinefrin, F V, fibrinogen, vWF, PF 4, βTG,
enzim hidrolase asam

Pembentukan fibrin
 exposed endothelial surface

platelets exposed to collagen

“activated”

release contents of cytoplasmic granules

adenosine diphosphate (ADP) thromboxane (Tx A2)

accelerates platelet vasoconstriction

aggregation/activation ↑ ADP release from
platelets
 Agregasi trombosit

Adesi trombosit
Trombosit

 Jml normal : 150.000 – 450.000/mmk

 Ukuran kecil (2-5 μm), sitoplasma kebiruan,
 Bagian tengahnya  khromomer [granula (+)
 Sekelilingnya  hialomer [granula (-)
Ukuran trombosit dianggap sbg indikator tingkat
produksi & destruksinya.

(rapid destruction & rapid turn over)

Biasanya trombosit muda ukurannya > besar  fungsi >

baik

Abnormalitas morfologi trombosit : Giant platelet,

ukurannya > 10 μm
Sindroma Bernard Soulier / sindroma giant platelet :
defek glikoprotein spesifik membran (mrpk reseptor GpIb/IX
untuk faktor von Willebrand), ukuran uniform
 Platelets Disorder

 Disorder of platelet number

– thrombocytopenia
– thrombocytosis
 Disorder of platelet function
 Disorder of platelets function

 defects of platelet adhesion

– inherited: vonWillebrandt’s disease , Bernard-Soulier syndrome
– acquired: uremia
 defects of platelet aggregation
– inherited: Glantzmann’s thrombasthenia
– acquired: dysproteinemia, drug ingestion (ticlopidin)
 defects of platelet release
– inherited: grey-platelet, Hermansky-Pudlak,Chediac-Higashi
syndr.
– acquired: cardiopulmonary bypass, myeloproliferative disorders,
drugs
 Kelainan Trombosit
Kuantitas
– Trombositopenia
 Imun: auto dan allo
 Non imun
– Essential Thrombocytemia
– Thrombocytosis
Kualitas
– Didapat
 Defisiensi vitamin C
 Obat NSAID
– Diturunkan
 Penyakit von Willebrand
 Kelainan Trombosit
Gejala

• Perdarahan berlebihan ok. trombositopenia atau

defek fungsi trombosit  mukosa (epistaksis, perdarahan
gigi
atau menorrhagia)
Atau menyerang kulit: purpura, petekhiae & ekhimosis

Gejala biasanya muncul: jumlah trombosit <

100.000/mmk
(10x109/l)
Tetapi mungkin lebih tinggi apabila terjadi penurunan
fungsi trombosit
 Kelainan Kuantitas Trombosit

Trombositopenia Trombosis
• Arterial
Didapat Kongenital
• Vena

ITP

Autoimmune Alloimmune Lain

• Akut • Obat
• Kronik • DIC
 Thrombocytosis

 Thrombocytosis resulting from myeloproliferation

– essential thrombocythemia
– polycythemia vera
– chronic myelogenous leukemia
– myeloid metaplasia
 Secondary (reactive) thrombocytosis
– systemic inflammation
– malignancy
– iron deficiency
– hemorrhage
– postsplenectomy
THROMBOCYTOPENIA
t.20.1 Causes of thrombocytopenia
Failure of marrow production
Reduced megakaryocytes
Marrow infiltration with tumor,infection or fibrosis
Marrow aplasia (fatty replacement) due to drugs,chemicals,or radiation
Congenital abnormalities (Wiskott-Aldrich syndrome, Fanconi’s syndrome)
Ineffective megakaryocytopoesis
Megaloblastic anemia
Myelodysplasia
Alcohol supression
Increased platelet destruction
Immune thrombocytopenia
Autoantibody-mediated : SLE, lymphomas,drugs,infections,ITP
Alloantibody-mediated : posttransfusion purpura, fetal-maternal incompatibility
Non imun thrombocytopenia
Disseminated Intravascular Coagulation
Thrombotic thrombocytopenic purpura
Mechanical (prosthetic materials)
Splenic sequestration
Hemodilution
Spurious
EDTA-pseudothrombocytopenia
t.27.2 Inherited thrombocytopenic Disorders
Autosomal recessive disorders
Bernard-Soulier syndrome
Congenital amegakaryocytic thrombocytopenia
Gray platelet syndrome
Thrombocytopenia with absent radius (TAR)
Syndrome
Autosomal dominant disorders
May-Hegglin anomaly
Quebec platelet disorders
Ebstein’s syndrome
Fechners’s syndrome
inclusions (dohle-
Sebastian’s syndrome
Montreal platelet syndrome
Hereditary macrothromcytopenia
Clinical features
Giant platelets
Abnormal GP Ib/V/IX
Abnormal RIPA
Severe thrombocytopenia
Absent megakaryocytes
Evolves to pancytopenia
No skeletal abnormalities
Large platelets
Absent platelet alpha-granules
Agranular pletelets by light microscopy
Variable agregation defects
Decreased megakaryocytes
Other skeletal abnormalities present
Large platelets
Leucocyte inclusions (dohle bodies)
Decreased alpha-granules proteins
Variable agregation defects
Defect-increased U-PA
Large platelets
Nephritis, cataracts, deafness
Variable agregation defects
Similar features as Epstein’s syndrome with leucocyte
bodies)
Large platelets
Lecocyte inclusions (dohle-bodies)
Large platelets
Severe thrombocytopenia
Spontaneuous platelet agregation
Large platelets
Deafness
Platelets express glycophorin A
 Trombositopenia
( <150.000/mmk)

Bawaan

• Jarang
• Bisa disebabkan ok. anemia aplastik bawaan,
• Trombositopenia dengan absent radii (TAR)
syndrome atau Wiskot-Aldrich syndrome
(trombositopenia dg. eksema dan
hipogammaglobulinemia)
• Ok. Infeksi kongenital (rubella, CMV)
 Causes of
Thrombocytopenia
Congenital Acquired

• Megakaryocytic hypoplasia • Immunothrombocytopenia

• TAR syndrome • Thrombotic thrombocytopenic
purpura
• Wiscott Aldrich syndrome • DIC
• Drugs
• Infections
• Splenomegaly
• Bone marrow suppression or
infiltration
• Aplastic anaemia
 Trombositopenia

Didapat

Sebab:

• Penurunan produksi trombosit

• Destruksi trombosit dipercepat
• Pemakaian meningkat
 Pemeriksaan Laboratorium

 Jumlah / Kuantitas
Pemeriksaan darah rutin  jmlh trombosit < 150 ribu
Sumsum tulang tidak mampu memproduksi trombosit
 pemeriksaan sumsum tulang (BMP)
Kerusakan berlebihan dlm darah  antibodi yg
ditujukan untuk trombosit dlm tubuh  Autoantibodi
dan Alloantibodi

 Mutu / Kualitas
Pembentukan sumbat
BT memanjang
Agregasi trombosit
 Thrombocytopenia
Decreased marrow production of megakariocytes
 congenital disorders
– thrombocytopenia with absent radii (TAR)
– Fanconi’s anemia
– May-Hegglin anomaly
 acquired disorders
– marrow infiltration with malignant cells
– marrow fibrosis
– aplastic and hypoplastic anemias ( idiopathic, drugs, toxins )
– deficiency states ( vitamin B12, folate, iron )
– paroxysmal nocturnal hemoglobinuria
Idiopathic Thrombocytopenic Purpura
(1)
 the most common cause of isolated
thrombocytopenia
 autoimmune disease with antiplatelet antibodies
and shortened platelets life span
 forms of ITP
acute ITP
– children (90% of pediatric case of immune
thrombocytopenia)
– preceded by viral infection
– spontaneous recovery within 4-6 weeks in 60% of patients
chronic ITP
– 20-40 years
– women predominance F:M=3:1
Idiopathic Thrombocytopenic Purpura
(2)
 Clinical features
– petechiae
– ecchymoses
– mucose membranes bleeding
– menorrhagia
– rare internal, intracranial bleeding
 Diagnosis
– platelet count <100G/l
– bleeding time - usually normal
– peripheral blood smear - large platelets
– bone marrow examination - normal or increased number of
megakariocytes
– antibodies against Gp IIb/IIIa
– shortened platelet survival
 Treatment of ITP

 not necessary unless platelets count > 20G/l or

there is extensive bleeding
 corticosteroids permanent responses -
30%
– prednisone 1mg/kg for 4-6 weeks
 splenectomy permanent responses -
60%
 immunosuppresive drugs
 intravenous immunoglobulins
 other - danazol, antiRhD
Pada ITP:
Apusan  penurunan jumlah trombosit (≤ 2 per
LPB) & kelainan morfologi
Megakariosit ss tl normal atau meningkat akan
tetapi dlm keadaan imatur / intact ( small immatur)
Pseudo trombositopenia:
tehnis, kdg2 akibat pengaruh EDTA
EDTA dependent platelet A.b

Satelitosis (krn pengaruh EDTA)

Menyebabkan Peudo/ Spurious trombositopenia
Terima kasih