Coagulation profile and its uses
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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.
Coagulation profile and its uses
- 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
- 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
- 8. Extrinsic Pathway • Begins on exposure to traumatized extravascular tissues that come in contact with blood – Release of tissue thromboplastin
- 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