12 (Haima=darah, stasis=berhenti) Yaitu Proses penghentian perdarahan secara spontan dari pembuluh darah yang mengalami kerusakan. HEMOSTASIS 3 HEMOSTASIS : “is the process which retains the blood within the vascular system”. Hemostatic process “is designed to repair the break and arrest hemorrhage”. The most immediate response to bleeding are from: 1. Vascular By Vasoconstriction mechanism, which decreases the blood flow through the injured blood vessel 2. Platelets Platelets clump together and adhere to the injured vessel in this area in order to form a plug, and further inhibit bleeding 3. The Coagulation factors By forming a fibrin meshwork or clot to stop the bleeding completely 4 Hemostasis diperankan oleh 3 faktor: 1. Faktor VASKULER 2. Faktor TROMBOSIT 3. Faktor PEMBEKUAN 5 Hemostasis diperankan oleh 3 faktor: 1. Faktor VASKULER 2. Faktor TROMBOSIT 3. Faktor PEMBEKUAN 6 Hemostasis diperankan oleh 3 faktor: 1. Faktor VASKULER 2. Faktor TROMBOSIT 3. Faktor PEMBEKUAN • Mekanisme Hemostasis 7 • Hemostasis or haemostasis (from the Ancient Greek: haimóstasis "styptic (drug)") is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage) • Hemostatis adalah proses dimana darah dalam sistem sirkulasi tergantung interaksi dari 5 faktor, yaitu : 1. dinding pembuluh darah, 2. trombosit, 3. faktor koagulasi, 4. sistem fibrinolisis, dan 5. inhibitor. Hemostasis bertujuan untuk menjaga agar darah tetap cair di dalam pembuluh, mencegah kehilangan darah karena luka, memperbaiki aliran darah selama proses penyembuhan luka. Hemostasis juga bertujuan untuk menghentikan dan mengontrol perdarahan dari pembuluh darah yang terluka 8 •Vasoconstriction of a damaged blood vessel slows the flow of blood and thus helps to limit blood loss. This process is mediated by: 1. Local controls. Vasoconstrictors such as thromboxane are released at the site of the injury. 2. Systemic control. Epinephrine released by the adrenal glands stimulates general vasoconstriction. 9 • Formation of a Platelet Plug. When a blood vessel is damaged, the blood is exposed to collagen fibers in the basement membrane of the vessel . Platelets stick to collagen and become activated. Activated platelets release chemicals such as ADP, and thromboxane, that cause the aggregation of more platelets to the site of injury. Platelet aggregation results in the formation of a platelet plug which acts to stem the flow of blood from the broken vessel. • It is essential that platelets become activated only at the site of a broken vessel. Otherwise activated platelets would form plugs and induce clots in inapropriate places. Healthy vessels secrete an enzyme called prostacyclin that functions to inhibit platelet activation and aggregation. 10 • Clotting of Blood The blood contains about a dozen clotting factors. These factors are proteins that exist in the blood in an inactive state, but can be called into action when tissues or blood vessels are damaged. The activation of clotting factors occurs in a sequential manner. The first factor in the sequence activates the second factor, which activates the third factor and so on. This series of reactions is called the clotting cascade. • Blood clotting is the transformation of liquid blood into a semisolid gel. Clots are made from fibers (polymers) of a protein called fibrin. Fibrin monomers come from an inactive precursor called fibrinogen. The body of the fibrinogen molecule has caps on its ends that mask fibrin-to-fibrin binding sites. If the caps are removed then fibrin monomers polymerize to form fibrin polymers. This process requires thrombin, the enzyme that converts fibrinogen to fibrin. This process also requires calcium, which acts as a kind of glue to hold the fibrin monomers to each other to form the polymeric fiber. The fibrin fibers form a loose meshwork that is stabilized by clotting factor XIII. The stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood. 11 12 FASE TROMBOSIT JUMLAH : 150.000. - 400.000/mm³ UMUR : + 10 HARI DIAMETER : 2 - 3 µ 1 MEGAKARIOSIT : 3.000 - 4.000 TROMBOSIT DIPENGARUHI : TROMBOPOIETIN (GINJAL) 7 - 8 x TIDAK BERINTI 13 1. ZONA PERIVER EXTERIOR COAT UNIT MEMBRANE SUB MEMBRANE FUNGSI: MERUPAKAN TEMPAT ADHESI & AGREGASI MENGANDUNG RESEPTOR UNTUK KOLAGEN, ADP, THROMBIN 14 FILAMEN SUB MEMBRANE MIKROTUBULI MIKRO FILAMEN SUMBER PROTEIN KONTRAKTIL FUNGSI : MEMBERI BENTUK TROMBOSIT PSEUDOPODI (KONTRAKSI WAKTU AGREGASI) 2. ZONA SOL-GEL 15 TERSEBAR BEBAS DALAM SITOPLASMA FUNGSI : RESPIRASI EKSKRESI PRODUKSI MENYIMPAN / MELEPASKAN ENERGI MENGATUR RESPON KIMIA TERHADAP STIMULUS 3. ZONA ORGANEL 16 3 MACAM GRANULA 1. LISOSOM ENZIM HIDROLITIK 2. GRANULA PADAT a. ATP b. ADP c. Ca ++ d. SEROTONIN e. EPINEPHRINE f. NOR-EPINEPHRINE 3. GRANULA ALFA a. ß-TROMBOGLOBULIN b. PLATELET FAKTOR 4 — Pƒ4 c. PLATELET DERIVED GROWTH FACTOR — PDGF d. GLIKO PEPTIDA MERANGSANG REPLIKASI OTOT HALUS DAN FIBROBLAS e. PROTEIN ~ PLASMA : - F.V - F. VIII - FIBRINOGEN - FIBRONECTIN f. TROMBOSPONDIN - TSP 17 vascular HEMOSTATIC PLUG = SUMBATAN PASE1 : - SUMBATAN AGREGASI - REVERSIBEL PASE 2 : - AGGREGASI SEKUNDER - IRREVERSIBEL UNTUK AGREGASI DIPERLUKAN: 1. ION KALSIUM 2. FIBRINOGEN 18 ADHESI PERLEKATAN TROMBOSIT PADA PERMUKAAN ASING TERUTAMA SERAT KALOGEN PERMUKAAN ASING 1. KOLLAGEN 2. MIKROFIBRIL 3. JARINGAN IKAT SUBENDOTEL. VIII : v WF (FACTOR VIII VON WILLEBRAND’S) 1. TROMBIN 2. ADP 3. KOLLAGEN 4. ADRENALIN 5. ADESI - AGREGASI MEMBRAN TROMBOSIT TROMBOSIT FOSFOLIPID ASAM ARA KHIDONAT PROSTA GLANDIN G2 ( PGG2) TROMBOKSAN A2 TX A2 REAKSI PELEPASAN AGREGASI FOSF LIPASE A2 SIKLO OKSIGENASE TROMBOKSAN SINTETASE 5-HT ADP TSP Β-TG PF 4 19 ADHESI Perlekatan Trombosit pada permukaan Asing 20 21 KELAINAN FAKTOR TROMBOSIT 22 I. KELAINAN JUMLAH A. TROMBOSITOSIS B. TROMBOSITEMIA C. TROMBOSITOPENIA II. KELAINAN FUNGSI A. KELAINAN ADESI B. KELAINAN PELEPASAN C. KELAINAN AGREGASI KELAIANAN TROMBOSIT 23 A. TROMBOSITOSIS : Thrombocytosis is the presence of high platelet counts in the blood, and can be either reactive or primary (also termed essential and caused by a myeloproliferative disease). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis in some patients. Peningkatan jumlah trombosit sementara - FISIOLOGI : - GERAK BADAN - PATOLOGIS : - TRAUMA - KEGANASAN - PERADANGAN RANGSANGAN HILANG --------> N 24 B. TROMBOSITEMIA : Thrombocythemia is a myeloproliferative blood disorder. It is characterized by the production of too many platelets in the bone marrow. Too many platelets make normal clotting of blood difficult. What causes thrombocythemia? There is no known cause for thrombocythemia. - TROMBOSITOSIS YANG MENETAP - FUNGSI : ABNORMAL 25 C. THROMBOCYTOPENIA : Thrombocytopenia is any disorder in which there are not enough platelets . Causes Thrombocytopenia is often divided into three major causes of low platelets: 1. Low production of platelets in the bone marrow 2. Increased breakdown of platelets in the bloodstream (called intravascular) 3. Increased breakdown of platelets in the spleen or liver (called extravascular) 26 TROMBOSITOPENIA STEM CELL POOL HYPOPLASIA IMMATURE MEGAKARYOEXT E POOL MATURE DISORDERED REGULATION THROMBOPOI TIC STIMULI INEFFECTIVE THROMBOPOISIS PLATELET PRODUCTION CIRCULATING PLATELET POOL SPLENIC PLATELET POOL NORMAL : 70% 30% 10 - 40% 60 - 90% ABNORMAL POOLING OR DISTRIBUTION PLATELET UTILIZATION ACCELERATED DESTRUCTION ABNORMA L : 27 IDIOPHATIC THROMBOCYTOPENIC PURPURA AKUT - ANAK - ANAK : 2 - 6 TAHUN - ♂ = ♀ - LAMANYA: 2 - 6 MINGGU - REMISI : 80 % - TROMBOSIT : <20.000/mm 3 KRONIK PUBERTAS - 50 TAHUN. ♂ > ♀ BEBERAPA BULAN – BEBERAPA TAHUN (-) FLUKTUASI 30.000 - 80.000/mm 3 ( I T P ) - UMUR TROMBOSIT : - 50.000/ mm 3 : - < 10.000/ mm 3 : - AUTOANTIBODI : MELEWATI PLASENTA 2 - 3 HARI (C r 51) 1 - 2 HARI < 2 JAM Ig G CONGENITAL ITP PADA ITP AKUT PADA MUSIM DINGIN INFEKSI SALURAN NAPAS ITP LABORATORIUM : TROMBOSIT - < 50.000/ mm 3 PERDARAHAN AN. DEFISIENSI FE - DITEMUKAN : MEGATROMBOSIT (GIANT TROMBOSIT) - WAKTU PERDARAHAN >> RETRAKSI BEKUAN JELEK - RUMPEL LEEDE TES : (+) - SS. TL MEGAKARIOSIT ; GRANULA << 28 KELAINAN FUNGSI TROMBOSIT 1. KELAINAN ADHESI TERHADAP KOLAGEN - EHLERS-DANLOS SYNDROME (KELAINAN VASKULER) 2. KELAINAN ADHESI TERHADAP SUBENDOTEL - SINDROMA BERNARD SOULIER (KELAINAN TROMBOSIT ) - SINDROMA VON WILLBRAND (KELAINAN PLASMA ) 3. KELAINAN PELEPASAN - SINDROMA HERMANSKY - PUDIAK - SINDROMAWISKOTT - ALDRICH DEFISIENSI STORAGE POOL - SINDROMA CHEDIAK - HIGASHI DEFISIENSI CYCLO - OXYGENASE (GANGGUAN MEKANIK PELEPASAN) PENYAKIT GLIKOGEN TIPE I (GANGGUAN METABOLISME NUCLEOTIDE) 4. KELAINAN AGREGASI ADP (KELAINAN TROMBOSIT) - THROMBASTHENIA GLANZMANN - AFIBRINOGEMIA