This document summarizes coagulation studies and disorders. It discusses the physiological clotting mechanism including the intrinsic, extrinsic, and common pathways. Common coagulation tests like prothrombin time, activated partial thromboplastin time, bleeding time, and mixing studies are outlined. Inherited disorders like hemophilia A and B and acquired disorders such as liver disease, vitamin K deficiency, and disseminated intravascular coagulation are summarized. The roles of natural coagulation inhibitors and how their deficiencies can cause hypercoagulable states are also highlighted.

1. Coagulation Studies
Dr. Akshay Agarwal
Moderator: Dr. Sangeeta Sharma

2. Important question
how many for
• Coffee?
• Tea??

3. Index
• Physiological Clotting Mechanism
• Coagulation tests
• Inherited coagulation disorders
• Acquired coagulation disorders

4. Mechanism of Blood Coagulation
• 3 essential steps:
– Clotting cascade to form prothrombin activator
– Formation of thrombin
– Formation of fibrin

5. Clotting Cascade
Intrinsic
pathway
Extrinsic
pathway
Common
pathway
Thrombin
formation
Fibrin
formation
clot

6. Intrinsic Pathway
• Begins on exposure of the blood to vascular
wall collagen which alters
– Factor XII and gets activated
– Platelets causing release of phospholipids

7. Intrinsic pathway
Prothrombin activator
Ca2+
Ca2+
Ca2+

8. Extrinsic Pathway
• Begins on exposure to traumatized
extravascular tissues that come in contact
with blood
– Release of tissue thromboplastin

9. Extrinsic Pathway
Prothrombin activator

10. Common Pathway
• 2 steps
– Conversion of Prothrombin to Thrombin
– Conversion of fibrinogen to fibrin

11. prothrombin
thrombin
fibrinogen Fibrinogen monomer
Fibrin fibers
Cross linked fibrin fibers
Fibrin stabilizing factor
Ca2+
Ca2+
Prothrombin
activator
Common Pathway

13. Some Facts about Clotting Factors
• All coagulation factors are made by
hepatocytes in the liver except
• Factor VIII which is made by endothelial cells
in the liver.
• Half life from 6 hours to 5 days
• The synthesis depends of availability of
Vitamin K

14. Vitamin K dependent coagulation
factors
• Prothrombin
• Factor VII
• Factor IX
• Factor X
• Protein C
• Protein S

15. Coagulation tests
• Prothrombin time (PT)
• Activated Partial thromboplastin time(aPTT)
• Bleeding time
• Clotting time
• Mixing study

16. Prothrombin Time
• Screens for abnormalities in both extrinsic
pathway and common pathway
• Normal range is 12-14 seconds
• Prolonged in:
– Vitamin K def. , warfarin therapy, DIC, liver failure
– Congenital afribrinogenemia
– Factor V & X def.

17. aPTT
• Screens for abnormalities in intrinsic and
common pathway
• Normal range is 25-40 seconds.
• Causes of prolonged aPTT
– DIC
– Hemophilia
– Liver disease
– Afribrigonemia
– Factor V, X

18. Bleeding time
• Finger prick method (Duke)
– Time taken from the commencement of bleeding to when it
ceases.
– Normally 1-3 mins
• Prolonged in
– Platelet defects - Thrombocytopenic purpura.
– Primary (Idiopathic) - Thrombocytopenic purpura
– Secondary - Thrombocytopenic purpura
– Vascular defects - Senile purpura
– Henoch Schonlein purpura
• Platelets are important in preventing small vessel bleeding
by causing vasoconstriction and platelet plug formation.

19. Clotting time
• Clotting time is the interval between the
moment when bleeding starts and the
moment when the fibrin thread is first seen
• Normal range is from 2-7 mins
• prolonged in
– Hemophilia A & B
– vitamin K deficiency, liver diseases
– disseminated intravascular coagulation,
overdosage of anticoagulants etc.

20. Mixing study
• Detects the presence of serum antibodies that
are neutralizing the coagulation factors
• Mix patient’s plasma and normal plasma sp.
• Perform aPTT assay at following intervals
Prolonged aPTT at Time 0 Time 1-2 hours at
37°C
Interpretation
corrected corrected Factor deficiency
Not corrected Not corrected LA or Heparin
corrected Not corrected Antibody inhibitor

21. Natural Inhibitors of Coagulation
• Antithrombin
– Major inhibitor of thrombin and factor Xa (CP) and
factor Ixa, Xia, XIIa (IP)
– Inherited deficiency leads to life long venous
thromboembolism
– It is a primary target for heparin based
anticoagulant therapy

22. • Protein C
– Acts by inactivating factor Va & VIIIa
• Protein S
– Cofactor for activated protein S
– Both C & S deficiencies lead to hypercoagulable
state.

23. Inherited Coagulation Disorder
• All factor deficiencies are autosomal recessive
except hemophilia A(factor VIII) & B (factor IX)
which are X-linked recessive.
• All will present with elevated aPTT except
– Factor VII def– elevated PT
– Factor XIII def – will not be detected by routine
tests.
All will present with bleeding tendencies

24. Hemophilia A & B
• Signs and symptoms
– Unexplained and excessive bleeding from cuts or
injuries, or after surgery or dental work
– Many large or deep bruises
– Unusual bleeding after vaccinations
– Pain, swelling or tightness in your joints
– Blood in your urine or stool
– Nosebleeds without a known cause
– In infants, unexplained irritability
• PTT will be prolonged and PT will be normal

25. Acquired coagulation disorders
• Due to decreased production
– Liver disease
– Vitamin K deficiency
• Due to increased consumption
– DIC
• Immune mediated
– Autoantibody against a specific clotting factor

26. Liver disease and Vitamin K def
• Liver disease evaluation is mandatory before
evaluating clotting factor deficiencies.
• Impaired function due to hepatitis and
cirrhosis will lead to decreased production
• Of note, factor VIII levels may be elevated in
hepatitis because it is an acute-phase reactant
• Vitamin K participates in post-translational
gamma-carboxylation of factors required for
their activity.

27. DIC
• Results from uncontrolled local or systemic
activation of coagulation leading to activation
and consumption of platelets, factors and
fibrinogen.

28. Diseases commonly associated with
DIC
• Metastatic carcinoma (Adenocarcinoma)
• Tissue injury
• Acute promyelocytic leukemia
• Sepsis
• Obstetric disorders
– Amniotic fluid embolism
– Retained fetus
– Placental abruption

29. Antibodies to coagulation Factors
• May develop after factor replacement therapy
or spontaneously.
• Lupus anticoagulant antibody is the most
common antibody against factor VIII and V
• Associated with both venous and arterial
thrombotic disease
• Can be detected by mixing studies

30. Other acquired conditions
• Systemic Amyloidosis
• Nephrotic Syndrome
• Hodgkin’s Lymphoma

31. Approach

32. Thank You