Marilah kita membiasakan diri menjadi manusia yang jujur

Marilah kita membiasakan diri menjadi manusia yang jujur. 1

Laboratory Approach to Patient with Hemostasis (Bleeding) Disorders Dr. Nadjwa ZD, Sp. PK-K 16 April 2012

Hemostasis Is the complex process by which the body spontaneously stop bleeding and maintains blood in the fluid state within the vascular compartment. Normal hemostasis: rapid & localized.

The major role of the hemostasis system is to maintain a complete balance of the body’s tendency toward clotting and bleeding.

: Hemostasis can be divided into 2 stages Primary Hemostasis • Platelet adhesion to exposed collagen within the endothelium of the vessel wall. Secondary Hemostasis • Enzymatic activation of the coagulation proteins to produce fibrin from fibrinogen stabilizing fragile clot formed during primary hemostasis. 5

Primary Hemostasis (platelet plug) Secondary Hemostasis (Hemostatic Plug)

Highly integrated & regulated Blood Vessel Natural Anticoagulant Platelets Hemostasis Fibrinolysis Coagulation Proteins 7

Hemostasis Disorders Bleeding Thrombosis Both • Vascular • Platelet (ITP) • Coagulation disorders (Hemophilia, v. WD) • Fibrinolysis • Natural anticoagulant • DIC 8

Approach to Hemostasis Disorders • Clinical History Taking Physical Examination - • Laboratory 9

Family History Symptom s History Taking Drugs Used Previous Disease 10

Physical Examination • • • Petechaie Ecchimosis Hematom Epistaxis Gingival bleeding 11

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Any Questions ? ? ?

Hemostasis Test Screening Confirmatory 20

Hemostasis Tests Screening assays in hemostasis: 1. Patients without any signs/symptoms preoperative 2. Monitoring of anticoagulant therapy 3. Disseminated Intravascular Coagulation 4. Thrombophilia 5. Inhibitor (Lupus Anticoagulant, Anti Phospholipid Antibody)

Hemostasis Screening Test 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Tourniquet Test Bleeding Time Clotting Time Clot Retraction Platelet Count* PT* APTT* Fibrinogen* Euglobulin Clot Lysis Test 11. D-Dimer Thrombelastography 22

Vessels • Tourniquette test, Bleeding Time Platelet • Count, Bleeding Time, Clot Retraction Coagulation Proteins Fibrinolytic system • CT, PT, a. PTT, Fibrinogen level • D-Dimer, Euglobulin Clot Lysis Time Natural • ATIII, Protein C/S Anticoagulant 23

Single, comprehensive hemostasis screening test Thrombelastography 24

Tourniquete Test = Capillary Resistance Test. = Rumpel Leede Test = Hess’s Test Principle : This test measures the ability of the capillaries to resist pressure. In healthy individu, the capillaries in the arm will resist a pressure of 100 mm. Hg. If the capillaries can not resist, they will break or rupture, tiny spot will then appear. These spots are hemorrhages or petechiae.

TOURNIQUET TEST SYSTOLIC DIASTOLIC 5 cm 100 mm. Hg 5 min Leave for 5 min • Normal : < 10 petechiae • > 10 petechiae abnormal, due to: – Increased capillary resistance – Decreased platelet number petechiae

BLEEDING TIME (Duke’s Method & Ivy’s Method) • Principle : The skin is incised, blood flowing out is aspirated with a filter paper, and then the time until hemostasis is measured. • Purpose : To evaluate platelet and vascular ability in performing platelet plug.

Interpretation • Time in minutes equals number of blots divided by 2 • When the blood spot becomes 1 mm or smaller, stop the stop watch. • If the bleeding doesn’t stop in 10 min. , discontinue testing. Indicate the result as 10 min or longer. • Cover the wound with a sterile gauze for a while, hemostasis should be confirmed, after which the patient may leave. • The size of the blood spot about 1 cm in diameter is desirable, but becomes larger in some cases. However bleeding usually stops for several minutes regardless of the size. • Don’t wipe off the blood. Gently touch. Note so as not to touch the wound.

CLOT RETRACTION Principle • When whole blood is allowed to clot spontaneously, the initial coagulum is composed of all elements of the blood. • With time the coagulum reduces in mass, and fluid serum is expressed from the clot, and its volume stated in %. • This is due to an action of platelets on the fibrin network.

Clotting Time Bedside Clotting Time Lee & White Method

BEDSIDE CLOTTING TIME Principle : • Record the time interval from the blood contact with glass surface, until fibrin network is performed at the room temperature. Sample : • Capillary blood

Clotting Time : Lee & White blood 3 ml 1 cc 37 o. C N : 5 – 11 min 1 cc 1 cc

Coagulation Tests Prothrombin Time (PT): Extrinsic and common pathway Activated Thrombin Time Partial (TT): Thromboplastin Time (APTT): conversion of Intrinsic and Fibrinogen to common Fibrin pathway 34

Coagulation Screening Tests: Related to the Coagulation Cascade 35

Coagulometer

Prothrombin Time (PT) • Screening test for the extrinsic and common pathways of coagulation (factors II, V, X). • Limited sensitivity to fibrinogen. • Normal range : 11 -13 sec

INR (International Normalized Ratio) To overcome some of the difficulties with the variability of thromboplastin normalizing the responses of thromboplastin reagents against an international standard. • INR = { PTpat -----PTn ISI }

ISI (International Sensitivity Index) • Needs to be developed for each thromboplastin reagent and instrument combination used in performing PT and calculation of INR. • Ideal reagent ISI < 1. 7

Activated Partial Thromboplastin Time (a. PTT) • Screening test for the intrinsic and common pathways of coagulation (factors XII, XI, IX, VIII, X, V and II). • Limited sensitivity to fibrinogen. • Maybe normal in some cases of v. WD • Normal range : < 35 sec

Thrombin Time (TT) • Identified stage 3 defects in the coagulation mechanism • Clinical significant Prolonged TT : – Decreased fibrinogen concentration – Presence of dysfunctional fibrinogen – Presence of heparin – Presence of FDP

Prothrombin Time Principle of the test : v Time required for the formation of a fibrin clot when plasma is added to a thromboplastin-calcium mixture. v Measure extrinsic and common pathway (FI, II, V, VII, X) 42

Prothrombin Time Purpose : 1. Evaluation of coagulation disorders 2. Evaluation of liver function 3. Monitoring anticoagulan therapy Result inform in : • Second • Percent • INR (International Normalized Ratio) PT prolonged if coagulation factors in extrinsic pathway decreased <30% 43

APTT Activated Partial Thromboplastin Time (APTT) Principle of the test : • Time required for the formation of a fibrin clot without additional thromboplastin. • Measured intrinsic and common pathway 44

D-Dimer Test Principle : Is the time required for the formation of a fibrin clot if thrombin is added. Affected by : • Concentration and fibrinogen reaction • Inhibitor (also FDP and heparin). 45

D-dimer

Thromboelastography • • • Screening & control therapy Easy to perform, no reagent needed, fast Record clot formation and converse to graph TEG ruler Conversion table

r r k m. a m. e = = m. a 20 mm 1. TEG NORMAL PATTERN k reaction time (start to amplitudo 1 mm) coagulation time (end of r to amplitudo 20 mm) maximum amplitudo (mm) maximum elasticity 100 x a m. e = ------100 - a

m. a 2. THROMBOCYTOPENIA r k r = normal k = normal/prolonged m. a. = shortened m. a 3. HYPERFIBRINOLYSIS r k r = normal k = normal m. a. = previously normal, but suddenly become shortened