GANGGUAN HEMOSTASIS : DIATESIS HEMORAGIS

Dr. dr. H. Irza Wahid, SpPD-KHOM, FINASIM

SubBagian Hematologi Onkologi Medik
Bagian Ilmu Penyakit Dalam
FK UNAND / RSUP Dr M Djamil Padang
 HEMOSTASIS  HOMEOSTASIS
Sistem Vaskular (Primary Hemostasis 1)
• Proses kontraksi pembuluh darah (vasokonstriksi) serta aktivasi trombosit dan
pembekuan darah.
Sistem Trombosit (Primary Hemostasis 2)
• Pembentukan dan stabilisasi sumbat trombosit melalui beberapa tahap yaitu
adesi trombosit, agregasi trombosit dan reaksi pelepasan
Sistem Pembekuan Darah (Secondary Hemostasis)
• Rangkaian reaksi enzimatik yang melibatkan protein plasma yang disebut
sebagai faktor pembekuan darah, fosfolipid dan ion kalsium.

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 1. THE PRIMARY HAEMOSTATIC SYSTEM:
Primary haemostasis
Platelet aggregation

trombosit
Adhesion
endothelial cells

sub endothelial tissue Activation

Vascular Aggregation
injury
White clot

Formation of
platelet plug

exposed sub
3
endothelial tissue
 2. SECONDARY HAEMOSTASIS

Prothrombin Thrombin Activation of the

Factor Xa coagulation cascade
Intrinsic Fibrinogen Fibrin
leads to generation of
Pathway Extrinsic thrombin and, in turn,
(colagen) Pathway (TF)
fibrin

Coagulation cascade
leads to clot formation

Clot
growth
Fibrin threads

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 Sistem Fibrinolisis
INTRINSIK EXTRINSIK EKSOGEN

XIIA, KALIKREIN UROKINASE

T-PA
AKTIFATOR PLASMINOGEN
(PAI-1)

PLASMINOGEN TERIKAT PLASMIN TERIKAT FIBRIN

FDP

PLASMINOGEN BEBAS PLASMIN BEBAS FIBRINOGEN

FC V, FC VIII

ANTI PLASMIN
RAHAYUNINGSIH,2009
HEMOSTASIS

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 PERDARAHAN NORMAL
• Luka  akibat cedera pembuluh darah  adanya
trauma  Normal
• Luka karena operasi / sunatan / cabut gigi  Normal
• Haid / Menstruasi  Normal
• Perdarahan saat melahirkan  Normal
 Perdarahan Abnormal
(DIATESIS HEMORAGIS )
Terbagi 2 :
1.Perdarahan ke dalam kulit atau jaringan  petekia, purpura, ekimosis,
hematoma
2.Perdarahan dg gejala darah keluar dari tubuh  epistaksis, perdarahan gusi,
hematemesis, melena, hematuria dan metroragia

Faktor yg mempengaruhi derajat perdarahan :

Individu
Derajat abnormalitas konsentrasi faktor dan atau fungsi faktor koagulasi
Jenis faktor koagulasi yang dipengaruhi/defisiensi
Heterozigot atau homozigot

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• hematoma
• petechia-spotted
(macula)
VASCULITIC
PURPURA
 PERDARAHAN ABNORMAL…???
TELUSURI PENYEBABNYA….☺

Vaskular

Trombosit Koagulasi
 A. KELAINAN PEMBULUH DARAH

• I. Keturunan
• • Telangiectasiae (Rendu-Osler-Weber disease)
• Aneurysm of fine vessels
• Ehlers-Danlos syndrome, Marfan’s syndrome,
retinocerebral angiomatosis (von Hippel-Lindau
syndrome), encephalotrigeminal angiomatosis (Sturge-
Kalisher-Weber syndrome)
• II. Didapat
• • Hemorrhagic vasculitis – Henoch-Schönlein purpura
• Immune vasculitis
• Systemic vasculitis
• Avitaminosis of vitamin C
 B. KELAINAN TROMBOSIT

•Thrombocytopenia (decrease in the number of platelets)

•I. Werlhof’s disease - autoimmune thrombocytopenic purpura
•II. Symptomatic
•• Immune (heteroimmune, isoimmune,)
• Toxic (in phosphorus poisoning etc.)
• Methaplastic (in hematological malignancies or myelocarcinosis)
• Drug-induced (cytostatics)
•Thrombocytopathy
•I. Congenital (deficiency of platelet membrane glycoprotein) –
Glanzmann's Thrombasthenia
•II. Acquired (normal platelet count in blood and bone marrow but its
functions are decreased)
•• Drugs (after intake of antiplatelet agents: aspirin, Ticlide®);
• Immune, toxic, septic processes;
• Hematological malignancies and anemias
 C. KELAINAN FAKTOR PEMBEKUAN

• Congenital disorders
• Von Willebrand disease –MC with minimal bleeding
• Factor VIII Deficiency - Hemophilia A or Classic Type
• Factor IX Deficiency – Hemophilia B
• Acquired disorders
• Vit. K deficiency
• Oral anti-coagulants
• Coumarin derivatives = warfarin – inhibit Vit. K
factors
• Liver diseases ↓ synthesis of factors
SCREENING TESTS FOR BLEEDING DISORDERS

Test Abnormality detected

Blood count and film Anaemia, leukaemia, disseminated
intravascular coagulation
Platelet count Thrombocytopenia
Activated partial thromboplastin time Deficiency of all coagulation factors
except VII, especially follows VIII and
IX;
heparin
Prothrombin time Deficiency of factors I, II, V, VII, and X;
warfarin

Thrombin time or fibrinogen Hypofibrinogenaemia or

dysfibrinogenaemia; heparin; fibrin
degradation products
Bleeding time Test of platelet-vessel wall interaction
 ITP: NEW TERMINOLOGY

• OLD: Idiopathic thrombocytopenic purpura

• NEW: Primary Immune Thrombocytopenia

• SOMETIME : Immune Thrombocytopenia

Rodeghiero F, et al. Blood 2009;113(11):2386-2393.

Not all ITP is Primary ITP:
Primary Secondary

Reproduced with permission from: Cines DB et al. Blood 2009;113:6511–6521

THE STEADY-STATE PLATELET COUNT IS DUE TO A BALANCE IN PLATELET
PRODUCTION, DESTRUCTION, AND SEQUESTRATION

• Platelet production1,2
Platelet • Produced by megakaryocytes
Production in the bone marrow

• Platelet destruction1
• Platelets survive in
circulation ~10 days
• Old platelets are removed by
Circulating macrophages in the spleen
Platelets and in the liver

• Platelet sequestration1
• One-third of platelets are
in the spleen
Platelet Platelet
Sequestration Destruction

1
Kaushansky K. In: Loscalzo J, Schaefer AI, eds. Thrombosis and Hemorrhage:
Lippincott Williams & Wilkins; 2003. 2Junt T, et al. Science. 2007;317(5845):1767-1770.
MECHANISM OF ITP
THERAPIES FOR THE TREATMENT OF ITP -OVERVIEW
 HEMOFILI
• Hemofilia adalah defisiensi faktor pembekuan darah yang
diturunkan secara X-linked recessive.
• Defisiensi F VIII : Hemofilia A
• 1 : 10.000 kelahiran bayi laki-laki
• Defisiensi F IX : Hemofilia B
• 1 : 50.000 kelahiran bayi laki-laki

• Sekitar 30% kasus merupakan mutasi spontan (bukan

diturunkan)
Carcao, et al. Hemophilia A and B. Basic Principles and Practice. 6th ed. Philadelphia, PA: Elsevier
Saunders; 2013:chap 137
PROSES HEMOSTASIS NORMAL

• Caused by mutation of the

FVIII or FIX, XI gene
• Classification of Haemophilia:
• Congenital Haemophilia -
inherited
• Haemophilia A – deficiency FVIII
• Haemophilia B – deficiency FIX
• Haemophilia with inhibitor

• Acquired Haemophilia
 Gejala Hemofilia

• Gejala hemofilia diantaranya perdarahan berulang dan sering kali disertai

nyeri

• Perdarahan dapat terjadi di seluruh tubuh, paling sering di sendi dan otot
• Gejala hemofilia pada hemofilia berat biasanya sudah timbul sejak tahun
pertama kehidupan

• Sebelum usia 1 tahun, pada hemofili berat manifestasinya biasanya

perdarahan subkutan (di bawah kulit) atau mukosa
PEMERIKSAAN LABORATORIUM

PT APTT BT Platelet Count

Normal Normal Normal Normal Normal

Hemofilia A Normal Prolonged Normal Normal

atau B atau C

VWD Normal Normal or Normal or Normal or

Prolonged Prolonged reduced
Diagnosis Pasti  Fc VIII/IX

Gradasi Hemofilia = Kadar faktor VIII/IX = Gejala Klinis

Classification Severe Moderate Mild

FVIII or FIX activity <1% 1% - 5% 6% - 40%

Pattern of bleeding ~2 - 4 per month ~4 - 6 per year Uncommon

episodes

Cause of bleeding Spontaneus Minor Trauma Major trauma, Surgery

episodes
 PENATALAKSANAAN HEMOFILIA A

• Belum ada terapi yang bersifat kausatif sehingga saat ini penderita hemofilia
mengidap penyakit ini sepanjang hidupnya
• Semakin sering mengalami perdarahan dan semakin lama perdarahan diatasi,
semakin besar kerusakan yang ditimbulkan.
• Kunci untuk perbaikan kesehatan dan kualitas hidup meliputi:
 Pencegahan pedarahan
 Pencegahan kerusakan permanen
• Terapi utama  replacement therapy (konsentrat FVIII)
Menggantikan faktor koagulasi yang mengalami defisiensi
PENATALAKSANAAN HEMOFILIA
 DIC
• Is not a disease entity but an event that can accompany various
disease processes
• Is an alteration in the blood clotting mechanism:abnormal
acceleration of the coagulation cascade, resulting in thrombosis
• As a result of the depletion of clotting factors, hemorrhage
occurs simultaneously
• Is a Paradoxical Clinical Presentation “clotting and
hemorrhage”

(Porth, C.M. (2004) Essentials of Pathophysiology) & (Otto, S. (2001).

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Thachil J et al, 2012

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BJH Guideline, 2009

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Thachil J et al, 2012

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Thachil J et al, 2012

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ISTH, 2007

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CLINICAL FEATURES
• Onset maybe Acute or Chronic
• Acute DIC
• Develops rapidly over a period of hours
• Presents with sudden bleeding from multiple sites
• Treated as a medical emergency
• Chronic DIC
• Develops over a period of months
• Maybe subclinical
• Eventually evolves into an acute DIC pattern

Otto, 2001
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 SIGNS AND SYMPTOMS
Most common sign of DIC is bleeding
 Manifested by ecchymosis, petechiae,and purpura
 Bleeding from multiple sites either oozing or frank bleeding
 Hematuria
 Cool and or mottled extremities may be noted
 Dyspnea and chest pain
(Porth, 2004) & (Otto, 2001)

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 TREATMENT MODALITIES
• Treat the underlying cause
• Provide supportive management of complications /
Support organ function
• Stop abnormal coagulation and control bleeding by
replacement of depleted blood and clotting components (FFP,
Kryopresipitat, Platelets,PRC)
• Medications can be used and choice depends on the patient’s
condition (Anticoagulant)

(Porth, C.M. (2004) Essentials of Pathophysiology) & (Otto, S. (2001).

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THANK YOU