Hemostasis ROUND cccccccc for 5+2 (1).pptx

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1. CLINICAL PATHOLOGY DEPARTMENT 1 Haemostasis

2. Components of the haemostatic response Blood vessels Platelets Coagulation factors Coagulation inhibitors Fibrinolysis

3. Hemostasis It is the process in circulation where the blood is maintained fluid in vessels and without major loss in case of injury. This defense mechanism involves vasoconstriction, platelet adhesion and aggregation to form a plug that is reinforced by fibrin for long term stability .

4. Causes of bleeding disorders I- Vascular system disorders II- Platelet disorders III- Coagulation disorders

5. When to do bleeding investigations? As a part of preoperative investigations. The patient is complaining of bleeding or hypercoagulability manifestations. The patient is on anticoagulant therapy.

6. Coagulation cascade

7. Lab tests for bleeding disorders SCREENING TESTS: 1. Complete blood count CBC . 2. Bleeding time BT : Normal value: 1 - 4 min. 3. Prothrombin time PT : Normal value: 10 - 14 sec. (International normalized ratio INR to standardize PT results among different labs). 4. Activated partial thromboplastin time APTT : Normal value: 30 - 40 sec. 5. Thrombin time TT : Normal value: 14 - 16 sec. Or measuring fibrinogen level CLINICAL PATHOLOGY DEPARTMENT 7

8. I- Vascular system disorders Lab diagnosis of vascular causes: BT: usually normal Hess test: > 15 purpuric spots Platelet count : normal Platelet function: normal PT/PTT/TT: Normal Hess test : Pressure is applied to the forearm with a sphygmomanometer cuff inflated to between systolic and diastolic BP for 10 min. After removing the cuff, the number of petechiae in a 5 cm diameter circle of the area under pressure is counted. Normally < 15 purpuric spots are seen. CLINICAL PATHOLOGY DEPARTMENT 8

9. II- Platelet disorders Lab investigations: 1. Bleeding Time: (prolonged with platelet function disorders). CBC & blood film examination. BM examination in case of thrombocytopenia. Anti-platelet antibodies. Screening tests for DIC:( in case of suspected clinical picture). Platelet aggregation studies: with ADP, adrenaline, collagen, ristocetin ); done by PFA-100 when CBC and platelet counts are normal with prolonged bleeding time. Platelet adhesion studies & nucleotide pool measurement. Von Willebrand factor assay & Factor VIII clotting assay. CLINICAL PATHOLOGY DEPARTMENT 9

10. III- Coagulation disorders A- Hereditary: Haemophilia A: due to deficiency of FVIII. Haemophilia B ( Christmas disease): due to deficiency of FIX Lab findings: CBC: normal BT: normal PT/INR: normal TT: normal PFA-100 tests: normal APTT: prolonged Specific factor VIII or IX assay: abnormal in haemophilia A & B respectively.

11. III- Coagulation disorders B- Acquired: 1. Vitamin K deficiency: - Lab findings: CBC: normal platelet count BT: normal. PT/INR: prolonged. APTT : prolonged. TT :normal Fibrinogen: normal with absent FDPs.

12. III- Coagulation disorders B- Acquired: 2. Liver disease: - Vitamin K-dependent factors ( II, VII, IX, X), protein C & S are reduced. - There is also decreased clearance of activated clotting factors leading to increased FDPs with normal D-Dimer test. 3. Antibodies to coagulation factors: - May occur in some immunological diseases (e.g. SLE, Rheumatoid arthritis), cancer, old age, allo antibodies to FVIII or IX in haemophiliacs.

13. III- Coagulation disorders B- Acquired: 4. DIC: Lab findings: CBC: decreased platelet count. BT: prolonged. PT/INR: prolonged. APTT : prolonged. TT : prolonged. Fibrinogen: low concentration. FDPs & D- Dimer: high levels Blood film examination: RBCs fragmentation ( microangiopathic haemolytic anaemia) In chronic DIC : Platelet count, PT, APTT may be normal with increased FDPs & D-Dimer

14. Monitoring of patients on anticoagulant therapy 1. Heparin therapy monitored by APTT : - It must be given in a dose sufficient to prolong PTT 1.5-2.5 times the upper limit of normal values. - APTT should be checked 4-6 hours after administration of heparin or a change in the infusion rate. 2. Oral anticoagulant ( Warfarin) therapy by PT : - Recommended therapeutic range of INR= 2.0-3.0 in DVT, pulmonary embolism, Atrial fibrillation, inherited thrombophilia or acute myocardial infarction. - Recommended therapeutic range of INR= 2.5-3.5 in recurrent embolism, mechanical prosthetic heart valves & anti-phospholipid syndrome. 3. LMWH (CLEXAN) monitored by anti factor X activity . CLINICAL PATHOLOGY DEPARTMENT 14

15. PROLONGED BLEEDING TIME CBC to diagnose thrombocytopenia. PT normal & PTT prolonged: VWD BM for thrombocytopenia. Platelet function tests (aggregometer): to diagnose qualitative platelet disorders, e.g. Glanzman’s disease. CLINICAL PATHOLOGY DEPARTMENT 15

16. Prolonged PTT 1. With Normal PT: - Defect in intrinsic system: FACTOR VIII, IX , XI, XII (factor VIII deficiency=hemophilia A ) (factor IX deficiency=hemophilia B Heparin therapy Lupus anticoagulant 2. Prolonged PT &PTT: Defect in the common pathway: Factor X,V, II,I CLINICAL PATHOLOGY DEPARTMENT 16

17. PROLONGED PT 1. With Normal PTT: Hereditary: Defect in extrinsic pathway: Factor VII deficiency Acquired: Hemorrhagic disease of the newborn due to vit K deficiency Liver disease (synthetic function of the liver) Oral anti-coagulant therapy. 2. Prolonged PT &PTT: Defect in the common pathway: factor X,V,II,I CLINICAL PATHOLOGY DEPARTMENT 17

18. Prolonged thrombin time In cases of fibrinogen defects : dysfibrinogenemia, afibrinogenemia, DIC CLINICAL PATHOLOGY DEPARTMENT 18

19. Interpretation Of Lab Tests Prolonged PT Deficiency of any factor of the extrinsic or common pathways: VII, X, V, II, I Vit K deficiency Liver disease Oral anticoagulant therapy DIC Prolonged PTT Deficiency of any factor of the intrinsic or common pathways: most common VIII, IX, V, X, II, I Presence of inhibitors. Heparin therapy DIC CLINICAL PATHOLOGY DEPARTMENT 19

20. Test panels needed for thrombotic disorders 20

21. CLINICAL PATHOLOGY DEPARTMENT 21 CASES

22. CLINICAL PATHOLOGY DEPARTMENT 22 Case1 What are the abnormalities in this coagulation report? What are the possible causes of this abnormality?

23. CLINICAL PATHOLOGY DEPARTMENT 23

24. CLINICAL PATHOLOGY DEPARTMENT 24 What are possible causes of increased PTT in this case ? Decreased factors of intrinsic and common pathway Heparin anticoagulant Presence of inhibitors as lupus anticoagulant Is there diagnostic tests? Measurement of specific factors activity Confirmation of lupus anticoagulant by correction of the PTT prolongation by adding phospholipid

25. CLINICAL PATHOLOGY DEPARTMENT 25 Case 2 What are the abnormalities in this coagulation report? What are the possible causes of this abnormality?

26. CLINICAL PATHOLOGY DEPARTMENT 26 What are possible causes of increased PT in this case ? Decreased factors of extrinsic and common pathway Oral anticoagulant as wrfarin ( Marivan ) Is there diagnostic tests? Measurement of specific factors activity

27. CLINICAL PATHOLOGY DEPARTMENT 27 Case 3 What are the abnormalities in this coagulation report? What are the possible causes of this abnormality?

28. CLINICAL PATHOLOGY DEPARTMENT 28 The following tests was performed to the patient. What is the possible diagnosis ? Acute pancreatitis What is the explanation for increased PT and PTT in this patient? Acute pancreatitis caused Disseminated intravascular coagulopathy (DIC)

29. CLINICAL PATHOLOGY DEPARTMENT 29 Is there diagnostic Tests for DIC ? D-dimer

30. CLINICAL PATHOLOGY DEPARTMENT 30 Case 4 This patient is taking Clexan ( low molecular weight heparins). What is your comment on her PT and PTT tests? It is accepted , because low molecular heparins do not affect Pt and PTT activity What is the test used for monitoring the effect of Clexan ? Anti-factor Xa (anti- FXa )

31. CLINICAL PATHOLOGY DEPARTMENT 31