faal hemostasis

FAAL HEMOSTASIS

Oleh :dr. Diah Hermayanti, SpPK

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TIU Memahami pemeriksaan faal hemostasis

TIK Memahami proses hemostasis

Memahami proses hemostasis pada jejas vaskuler

Memahami dan dapat menginterpretasipemeriksaan laboratorium hemostasis

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HEMOSTASIS Proses fisiologis yg seimbang :

mencegah perdarahan >>> (setelah perlukaan vaskuler)

mempertahankan sirkulasi (dg menjaga darah tetap cair)

Trombosis Perdarahan

KOAGULASI HEMOSTASIS FIBRINOLISIS

Perdarahan Trombosis

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TAHAPAN PROSES BILA TJD TRAUMA VASKULER :

1. Vasokonstriksi

2. Primary hemostasis (detik)

3. Secondary hemostasis (menit)

4. Proses perbaikan & fibrinolisis

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PRIM ARY HEMOSTASIS

SECONDARY HEMOSTASIS

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7PROSES HEMOSTASIS

Vascularinjury

Platelet adhesion&

Release reaction

Platelet aggregation

PrimaryHemostatic plug

Secondary hemostatic plug(stable hemostatic plug)

Vasoconstriction Coagulationcascade

Tissue factor

Release ofPlatelet phopholipid

Thrombin

Fibrin

Blood flow ↓

Exposure of colagen

Serotonin

TX2, ADP

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8JALUR KOAGULASI DARAH

X

Xa + Va + phospholipid

XIIIII (prothrombin) IIa (thrombin)

XIIIa

I (fibrinogen) Fibrin Cross-linkedfibrin

TF + VIIaIX IXa

+VIII VIIIa

XI XIa

JALUR EKSTRINSIKJALUR INTRINSIK

Surface contac : HMWK Prekalikrein

Ca 2+

Ca 2+

Ca 2+

PL

XII XIIa

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FAKTOR KOAGULASI PLASMA

Faktor Nama

I FibrinogenII ProthrombinIII Tissue thromboplastinIV CalciumV Proaccelerin (labile factor)VII Proconvertin (stable factor)VIII Antihemophilic A factorIX Antihemophilic B factorX Stuart factorXI Plasma thromboplastin antecedentXII Hageman factor, contact factorXIII Fibrin stabilizing factor

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10JALUR FIBRINOLISIS

PLASMINOGEN

PLASMIN

Aktivator :o intrinsik : F.XII, kinin, trombin, urokinaseoEkstrinsik : t-PA, excercise, stressoTerapeutik : streptokinase

Anti aktivator :o C-1 Esterase inhibitoro PAI (plaminogen activator inhibitor )

FIBRIN FIBRIN DEGRADATION PRODUCTS (FDP)

Antiplasmin :o α2 antiplasmino α2 makroglobulin

Antiplasmin :o α2 antiplasmino α2 makroglobulin

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11PEMERIKSAAN LABORATORIUM

UNTUK MENILAI FAAL HEMOSTASIS

TUJUAN PEMBELAJARAN : Memahami prinsip pemeriksaan laboratorik hemostasis sederhana Mengkaitkan dg penyakit gangguan faal hemostasis (interpretasi & diagnostik)

Pendekatan :1. Anamnesis2. Pemeriksaan fisik3. Laboratorik

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12ENDOTEL MENGATUR FLUIDITAS HEMOSTASIS

BLOOD FLOW

Pro-trombotik : trombosit-vaskuler koagulasi plasma

Anti-trombotik : antikoagulan inhibitor fibrinolisis

Bleeding Trombosis

Trombosis Bleeding

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14ANAMNESIS Eksplorasi riwayat penyakit :

keturunan (herediter) didapat (acquired )

Anamnesa :1.Perdarahan circumsisi / tali pusat / persalinan ?2.Epistaksis / memar (easy bruising) ?; persendian (joint bleeding)?3.Perdarahan cabut gigi ?4.Menstruasi berkepanjangan ?5.Memar tanpa sebab yg jelas ?6.Darah di urin / feses ?7.Riwayat transfusi (terutama trombosit) ?8.Minum obat aspirin / derivatnya (7 hari terakhir ) ?

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PEMERIKSAAN FISIK

PTEKIAE : bercak merah kecil di kulit (Ф ujung jarum) (ekstravasasi darah dari vaskuler yg intak karena peningkatan permeabilitas)

PURPURA : kumpulan ptekiae

EKIMOSIS : area lebam (kebiruan) (Ф > purpura)

HEMATOMA : lebam luas yg menginfiltrasi subkutan atau otot, shg menyebabkan deformitas

HEMARTROSIS : perdarahan di persendian (perdarahan berat) gangguan koagulasi (hemofili)

HEMATURIA : perdarahan di urin (trauma lokal batu; overdosis antikoagulan; hemofili)

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16PEMERIKSAAN LABORATORIUM

TES SKRINING :

Jumlah & morfologi menilai primary trombosit hemostatic plug Bleeding time

Clotting time menilai koagulasi / aPTT (activated partial secondary hemostatic thromboplastin time) plug PT (prothrombin time)

TES KONFIRMASI / KHUSUS : Fungsi trombosit (adesi, sekresi, agregasi) Pengukuran faktor koagulan Pemeriksaan inhibitor

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17TES SKRINING PRIMARY HEMOSTATIC PLUG

(TROMBOSIT-VASKULER )

Tujuan : menentukan kelainan trombosit / vaskuler

TROMBOSIT :o morfologio jumlaho fungsi

Capillary resistance test (Rumple-Leed test)

Bleeding time (Ivy ; Duke)

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18RUMPLE – LEEDE TEST

(Capillary resistance test)

VOLAR(dibaca 15 menit setelahTekanan dilepas)

HASIL :(-) : jumlah ptekiae < 1010-20 : meragukan(+) : > 20

POSITIF :1.Trombositopenia2.Gangguan vaskuler3.Gangguan fungsi trombosit

Systole

Diastole

5 minutes(± 100 mmHg)

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19BLEEDING TIME / BT(waktu perdarahan)

BT menilai Pembentukan hemostatic plug

1. Kelainan trombosit2. Kelainan vaskuler

Normal (Duke) : 1-3 menit

Memanjang :1.Kelainan konstriksi vaskuler2.Trombositopenia3.Gangguan adhesi trombosit4.Gangguan pelepasan ADP trombosit5.Gangguan aggregasi trombosit6.Gangguan avaibilitas PF3

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40 mmHgCupingtelinga

Volar

Cara DukeNormal

1-3 menit

Cara IvyNormal

1-7 menit

Normal Abnormal(memanjang)

½

11½

2 2½3

Start Start Bleeding timemenilai :

Dacie et al. 1975, Hirsh et al. 1979, Sirridge et al. 1983

Kertassaring

Bleeding Time

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21TES SKRINING KOAGULASI

(secondary hemostatic plug /fibrin clot formation)

Tujuan : deteksi gangguan koagulasi menentukan tahapan proses yg terganggu

Pemeriksaan : clotting/coagulation time (CT) aPTT (activated partial thromboplastin time) PPT (plasma prothrombin time) TT (thrombin time)

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CLOTTING FACTOR (CT)

MENILAI pembentukan tahap awal dr thrombin WAKTU untuk menghasilkan bekuan yg terlihat mata

(Jalur intrinsik & jalur umum)

CT >>> - defisiensi faktor pembekuan yg berat pada jalur intrinsik dan jalur umum (common pathway) (Tidak dipengaruhi oleh F VII)- pemakaian heparin

Normal : 5-15 ‘

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ACTIVATED PARTIAL THROMBOPLASTIN TIME (aPTT)

Tes koagulasijalur intrinsik (prekalikrein, HMWK, F. XII,XI, IX, VIII) jalur umum (F. X,V, prothrombin, fibrinogen)

aPTT deteksi :1. Defisiensi faktor di atas2. Skrining antikoagulan lupus3. Monitor terapi heparin

Normal : 25 - 39 detik (tergantung laboratorium)

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PLASMA PROTHROMBIN TIME (PPT)

Tes koagulasiJalur ekstrinsik (F.VII)Jalur umum ( F.X, V, II, I)

PPT deteksi :1. kontrol antikoagulan oral koumarin

(F.II, VII, X adalah vit K dependent ygterdepresi oleh obat koumarin)

2. defisiensi F. VII & X

Normal : 10 -14 detik (tergantung laboratorium)

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INTERNATIONAL NORMALISED RATIO(INR)

Dipergunakan untuk menstandarsisasi hasil pengukuran PPTyg sangat tergantung pada masing-masing laboratorium

INR = PTtest ISI

PTnormal

ISI : International sensitivity index (tergantung batch)

Normal : 0,8 -1,2 (normal, tanpa terapi antikoagulan)2 - 3 (pengobatan antikoagulan/Warfarin)

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THROMBINE TIME (TT)

Tes koagulasimengukur kecepatan pembentukan fibrin

TT abnormal :1. defisiensi F.I (fibrinogen)2. kelainan kualitatif fibrinogen3. heparin4. disseminated intravascular coagulation (DIC)

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28PENDEKATAN(Anamnesa, fisik, laboratorik)

Gg.Perdarahan Gg.Trombosis (bleeding disorders) (thrombotic disorders)

Congenital(herediter)

Acquired(didapat)

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29Gg. KOAGULASI (CLOTTING DISORDERS)

HEREDITER

Von Willebrand synd. 1:200 - 5.000Hemophilia A (VIII def) 1:5.000 - 10.000Hemophilia B (IX def) 1:50.000 - 100.000Factor XI deficiency 1:100.000 - 500.000Factor II deficiency < 1:106

Factor V deficiency < 1:106

Factor VII deficiency < 1:106

Factor X deficiency < 1:106

Factor XII deficiency < 1:106

Prekallikrein deficiency < 1:106

HMWK deficiency < 1:106

Afibrinogenia < 1:106

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Gg. KOAGULASI DIDAPAT (ACQUIRED)

ACQUIRED DEFICIENCY STATE :Liver diseasevit K deficiencyoral anticoagulantamyloidosisconsumptive coagulopathieshematinsnake venom

INHIBITION of CLOT FORMATION :Heparin lupus anticoagulantmacromolecules neutralizing factor inhibitors(dextran) non- neutralizing factor inhibitorsdysfibrinogenemia

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31DIFERENSIAL SKRINING KOAGULASI

Prolonged APTT Prolonged PT Prolonged APTT&PT

COMMONHeparin Vit K deficiency Vit K deficiencyLupus anticoagulant Oral anticoagulant Oral anticoagulantHemophilia A Liver disease Liver diseaseHemophilia B Consumptive VWD (with long BT) -coagulopathies

UNCOMMONSpecific factor inhibitors Factor VII deficiency F. II, V, or X defF. XI or XII deficiency Hereditary –Prekalikrein def dysfibrinogenemiaHMWK deficiency Afibrinogenemia

Specific factor- inhibitorsAmyloidosis

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Gangguan kuantitas : Jumlah turun

(trombositopenia) :- produksi <<- usia <;

destruksi >- pooling >> (di Limpa)

Jumlah meningkat(trombositosis)

Gangguan kualitas(trombositopati) :

Primer Sekunder

Fungsi yg terganggu : Adesi Release Agregasi Koagulasi

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GANGGUAN TROMBOSIT

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KELAINAN TROMBOSIT HEREDITER

Kelainan Laboratorium

Kelainan adhesivon Willebrand synd vWF, Platelet aggregationBernard-Soulier synd vWF, Platelet aggregationCollagen disorders BT, normal platelet aggregation

Kelainan agregasiGlansmann’s thrombasthenia BT, platelet aggregation, GP IIB-IIIAAfibrinogenemia BT, platelet aggregation, fibrinogen

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KELAINAN TROMBOSIT DIDAPAT(mengganggu fungsi trombosit)

Obat (aspirin, indometasin, ibuprofen, penisilin)Antibodi trombosit

Penyakit ginjalMyeloproliferative disorders

Myeloma Fibrinolysis

MacromoleculesFibrin split product

Monoclonal proteinsIn vivo release

hypothyroidism

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GANGGUAN TROMBOSIS

HEREDITER

Sistem Kelainan

Serine protease inhibitor Defisiensi Antitrombin III(SERPINS) Def. Heparin kofaktor II

Sistem fibrinolitik Def. Protein C heterozygousDef. Protein C homozygousDef. Protein S heterozygous

Trombosit Hyperactive platelet synd

Miscellaneous dll

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Gangguan Trombotik Didapat

Kondisi sistemik : Kelainan hemostatik :

Atherosclerotic vascular disease Lupus anticoagulantdiabetes mellitus DICmalignat neoplasma Thrombotic thrombocyto-myeloproliferative disorders penic purpuraparoxismal nocturnal hemoglobinuria Hemolytic-uremic syndestrogen & oral contraceptive Snake venomsPregnancy Coagulation factor-venous stasis concentratesnephrotic syndromehyperlipidemiaartificial vascular prostheseshyperviscosity

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39COMPLEX HEMOSTATIC DISORDERS

DISORDER LABORATORY MANIFESTATIONS

Disseminated intravascular thrombocytopenia low fibrinogenCoagulation (DIC) long PT long APTT

increased FDPs low AT III

Thrombotic thrombocytopenic thrombocytopenia normal fibrinogen Purpura (TTP) microangiopathic peripheral blood filmHemolytic uremic syndrome normal AT III (HUS)

Liver disease long PT low AT IIInormal to low fibrinogen

Brandt 1999

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40DISSEMINATED INTRAVASCULAR COAGULATION(DIC)

INITIATING STIMULUS

THROMBIN PLASMIN

FIBRIN PLATELET FACTOR FIBRINOLYSISFORMATION ACTIVATION CONSUMPTION

MICROVASCULAR HEMORRHAGETHROMBOSIS

FIBRINOGEN PLATELETDEPLETION DEPLETION

HEMORRHAGE

ACTIVATION ACTIVATION

Brandt 1999

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41 DIC STIMULATOR :

1.Tissue factor coagulants :traumahemolysiscarcinoma

2.Factor producing platelet aggregation :septicemiauremiaimmune complexes

3.Endothelial damage :burnvasculitis

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42GANGGUAN HEMOSTATIK

PADA PENYAKIT LIVER

ABNORMALITAS MANIFESTASI LABORATORIUM MANIFESTASI KLINIK

TROMBOSITOPENI TROMBOSITOPENI PERDARAHAN

SINTESA FAKTOR PT & APTT >>>>> PERDARAHANKOAGULASI <<<

SINTESA PROTEIN AT III <<, PROTEIN C << THROMBOSIS, DICREGULATOR <<<

DISFIBRINOGENEMIA TT / PT / APTT >>>>> NONE / PERDARAHANFDP FALSE (+) RINGAN

ABNORMAL PROTEIN PT >>>> PERDARAHAN (?)DEPENDEN VIT K

Brandt, 1999

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VITAMIN – K DEFICIENCY

VIT-K dibutuhkan oleh hati untuk sintesa :Vit-K dependent coagulation factors(F. II , VII, IX, X)

SUMBER VIT-K :- makanan (tu. Tumbuhan)- sifat : fat soluble

PENYEBAB DEFISIENSI :- malabsorpsi lemak- obstruksi bilier (gg.sekresi empedu)- pancreatic disease (gg.produksi lipase pankreas)

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RINGKASAN

TES MENILAI INTEGRITAS

Bleeding time (BT)Capilary resistance test

Trombosit – Vaskuler

Thrombine time (TT)

Fibrinogen /fibrine conversion

Prothrombine time (PT)

Jalur ekstrinsik

Activated partial thromboplastin time (APTT)

Jalur intrinsik

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