1. Hemostasis and Coagulation1

2. Intended Learning Outcomes (ILOs)
Discuss laboratory evaluation of hemostatic function.
Design a plan to diagnose a case of thrombocytopenia.
Recall causes of prolonged prothrombin time (PT)
Recall causes of prolonged activated partial thromboplastin time (APTT)
Demonestrate laboratory profile of Von Willebrand Disease.
- Interpret various cases characterized by hemostatic function defect.

3. Components of hemostasis
Hemostasis: is the process by which bleeding is arrested after injury to blood vessels
Normal hemostasis requires the interaction of platelets and clotting cascade with normal blood vessels

4. Balance in Hemostasis
Haemostasis depends on a delicate balance between procoagulant and anticoagulant mechanisms
A disruption of this unique balance may cause bleeding or thrombosis
Hemostasis
Anticoagulant
Procoagulant
Thrombosis
Anticoagulant
Procoagulant
Bleeding
Anticoagulant
Procoagulant

5. Mechanism of coagulation
Intrinsic pathway
Extrinsic pathway
XIIa
contact factors TF
XIa
VIIa
lXa Xa
VIIIa
Test: PTT
Test: PT Va
Ca++
finronolysis II
IIa
Fibrinogen
Fibrin

6. Presentation Bleeding Tendency:
Excessive bleeding (spontaneous/ after injury)
Easy hematoma formation after minor trauma
Recurrent epistaxis
Menorrhagia
Abnormal bleeding during operation , or post operative
Petichae, purpuric eruption, ecchymosis
Thrombosis:
Deep venous thrombosis (DVT)

7. LABORATORY EVALUATION OF HEMOSTATIC FUNCTION
Screening tests: done for all suspected patients
Bleeding time
Platelet count
Prothombin time (PT)
Partial thromboplastin time (PTT)
Thrombin time (TT)
Specific tests : done according to results of screening tests 7

8. BLEEDING TIME Time needed to stop bleeding after induced needle prick
Affected by
Platelet count
Platelet function
Vessel wall
Normal range: Ivy’s method: up to 7 min
Note: it is not a sensitive test for minor or even moderate abnormality. 8

9. Bleeding time: BT Causes of prolonged bleeding time:
1-Thrombocytopenia (moderate or severe).
2-Disorders of platelet function.
*VWD
*Glanzmann’s disease
*Bernard Soulier syndrome
3-Vascular abnormalities

10. PLATELET COUNT Normal platelet count = 150-400 x109/L
A part of complete blood picture (CBC)
Performed by electronic counters or
manually
Note:
Any case of unexpected very low platelet count should be rechecked particularly in infants and young children when sampling is difficult. 10

11. Investigation of a case of thrombocytopenia
History
CBC
Bone Marrow
ANA

12. QUALITATIVE PLATELET DEFECT
In a case presenting with purpura and normal platelet count and other coagulation tests you have to suspect defective platelet functions. 12

13. Tests
Morphology of platelet in smear
Platelet aggregation

14. PROTHROMBIN TIME (PT) Test for extrinsic pathway (FVII, FII, FV, X)
[majority are vitamin K dependent factor].
Used for monitoring oral anticoagulant therapy and used as a liver function test
Normal range: sec 14

15. Prothrombin Time PT
Tissue extract ca
Fibrin clot
Plasma

16. Causes of prolonged PT Oral anticoagulants Liver disease
Vit K deficiency (FII, VII , IX and X )
Congenital deficiency of factors involved in extrinsic pathway.
DIC
inhibitors 16

17. Reporting Of PT Test
Example Patient : 12 sec Control : 11 sec INR : 1.1

18. PARTIAL THROMBOPLASTIN (PTT)
It is a test for intrinsic pathway of blood coagulation (FVIII, FIX, FXI, FXII, FII, FV, X). It is the test Used for patients receiving heparin therapy Normal range: sec 18

19. Causes of prolonged PTT19

20. Causes of prolonged PTT
Heparin
Deficiency of factors involved in intrinsic pathway, usually congenital: Hemophilia A Hemophilia B and von Willebrand disease)
DIC
Massive transfusion (labile FV, FVIII)
Inhibitors 20

21. BT PT PTT Platelet count Platelet function Other tests ITP Glanzman
disease
Bernard Soulier S
Hemoph A
Hemoph B
vWD
DIC 21

22. To summarize

23. Investigation Of Bleeding Disorder

24. APTT Bleeding Time (BT) Prolonged Normal Platelets Count Platelets
Function
Blood vessels
Check PT
APTT
APTT
Hemophilia
Heparin PT
Oral AC

25. Prothrombin Time (PT) Prolonged Oral anticoagulant
Vitamin K deficiency
Liver Disease
DIC
inhibitors

26. Activated Partial Thromboplastin Time (aPTT) Heparin anticoagulant
Prolonged
Heparin anticoagulant
Hemophilia
Massive Liver Disease
DIC
inhibitors
Von Willebrand Disease

27. Prolonged (BT) + Prolonged APTT+ Normal PT
Von Willebrand Disease
Prolonged (BT) + Prolonged APTT+ Prolonged PT
Massive Liver Disease
DIC

28. Case study

29. bleeding time 10 min (normal, 2-7 min)
Case 1 A 32-years old woman observes the presence of multiple petechiae, purpura and ecchymosis rashes when she wakes up in the morning . She had a history of epistaxis requiring cauterization.
platelet count x 109/L
bleeding time min (normal, 2-7 min)
This woman might be suffering from:
a-Immune thrombocytopenic purpura
b-Von Willebrand disease
c-Glanzmann’s disease
d-a, b & c
e-b & c 29

30. bleeding time 10 min (normal, 2-7 min)
Case 2 A 19-years old woman complained of prolonged menstrual bleeding. She had a history of epistaxis requiring cauterization.
platelet count x 109/L
bleeding time min (normal, 2-7 min)
This woman might be suffering from:
a-immune thrombocytopenic purpura
b-von Willebrand disease
c-Glanzmann’s disease
d- a, b & c
e-b & c 30

31. Case 3
A 3 year old boy presents with a painful left elbow after mild trauma. Evaluation reveals a hemarthrosis.
Platelets count is 190X109/L
BT & PT are normal
PTT is prolonged
Which of the following is the most likely diagnosis?
hemophilia A
Von Willebrand Disease
Bernard Soulier syndrome
immune thrombocytopenic purpura
aspirin intake

32. Case 4 A 30 year old man presents with easy bruising
PT seconds (normal, seconds)
PTT seconds (normal, seconds)
BT minutes (normal 2-7 minutes)
Which of the following is the most likely diagnosis?
hemophilia A
hemophilia B
von Willebrand disease
immune thrombocytopenic purpura
aspirin intake 32

33. CASE 5
A 42 year-old man brought to the emergency room with severe second- and third-degree burns.
SCREENING COAGULATION LABORATORY RESULTS
PT= 17 sec (Normal )
aPTT= 49 sec (Normal )
Platelet count= 20,000 /μL
hemophilia A
hemophilia B
von Willebrand disease
DIC
Glanzmann’s disease

34. BT PT PTT Platelet count Platelet function Other tests ITP P N
Bone marrow
Glanzman
disease
Defect aggreg
Hemoph A
FVIII assay
Hemoph B
FIX assay
vWD
FVIII, vWF
DIC
Fibrinogen FDPs 34

35. THROMBOPHILIA

36. Group of disorders that predispose to venous thrombosis
THROMBOPHILIA
Heritable thrombophilia
Acquired thrombophilia
Group of disorders that predispose to venous thrombosis

37. INHERETED THROMBOPHILIA
ACQUIRED THROMBOPHILIA
Anti-thrombin deficiency
Iatrogenic: surgery -hormonal therapy – chemo/radiotherapy – drugs
Protein C deficiency
Environmental: Age - obesity -pregnancy – trauma – Immobility
Protein S deficiency
Disease related: APS – Neoplasia – MPN – PNH – TTP – Inflammation – stroke -SCD
Factor V leiden (FV R 506 Q)
Prothrombin G20210A mutation
MTHFR

38. DIAGNOSIS HEREDITARY THROMBOPHILIA Assays for: AT-III, Protein C
Protein S
Molecular studies for:
FV leiden
Prothrombin G20210A
Homocysteinaemia
ACQUIRED THROMBOPHILIA:
Tests for APS, Lupus Anti-coagulant

39. Thank You