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Haemorrhage and its
management
introduction
Prolonged or uncontrolled bleeding is often
referred to as hemorrhage.
Blood carries oxygen and nutrients to the tissues
and is vital for body functions.
 Any damage to the vasculature leads to the
outflow of blood.
Escape of blood from a blood vessel.
Hemostasis Mechanism
1. VASCULAR PHASE
2. PLATELET PHASE
3. COAGULATION PHASE
factors affecting HEMOSTASIS
 Vessel Wall Integrity
 Adequate Numbers of Platelets
 Proper Functioning Platelets
 Adequate Levels of Clotting Factors
 Proper Function of Fibrinolytic Pathway
CLASSIFICATION OF HEMORRHAGE
1. Depending on the SOURCE OF BLEEDING:
i) External Hemorrhage: When bleeding is revealed and seen outside,
e.g. epistaxis.
ii) Internal Hemorrhage: Bleeding is concealed and not seen outside,
e.g. intracranial hematoma.
2. Depending on the NATURE OF BLEEDING VESSEL:
i) Arterial Hemorrhage: Bright red in color. Blood emitted as a jet with
each heartbeat.
ii) Venous Hemorrhage: Dark red in color. Blood flow is steady.
iii) Capillary Hemorrhage: Bright red in color. Generalized ooze of
blood instead of blood flow.
3. Depending upon TIME OF HEMORRHAGE:
i) Primary Hemorrhage: Occurs at the time of trauma or surgery.
ii) Reactionary Hemorrhage: Occurs within 24 hours of trauma or operation.
iii) Secondary Hemorrhage: Occurs after 7 – 14 days of trauma oroperation.
4. Depending upon VOLUME OF BLOOD LOSS:
i) Mild Hemorrhage: Blood loss ≤ 500 mL.
ii) Moderate Hemorrhage: Blood loss 500 – 1000 mL.
iii) Severe Hemorrhage: Blood loss ≥ 1 L.
CLASSIFICATION OF HEMORRHAGE
5. Depending upon SPEED OF BLOOD LOSS:
i) Acute Hemorrhage: Massive bleeding in short span of time.
ii) Chronic Hemorrhage: Slow bleeding small in quantity for long time.
6. Depending upon PERCENTAGE OF BLOOD LOSS:
i) Class I: Up to 15%.
ii)Class II: Between 15 – 30%.
iii) Class III: Between 30 – 40%.
iv) Class IV: More than 40%.
ETIOLOGY
 Trauma.
 Infections.
 Congenital malformations.
 Surgical (intraoperative/postoperative).
 Due to systemic diseases (viral infection, scurvy, allergy).
 Abnormalities in clotting factor (hemophilia A, multiple
myeloma).
 Abnormalities in platelets (leukemia, ITP, thrombocytosis,
thrombocytopenia).
Clinical features
Pallor, thirsty, cyanosis
Tachycardia, tachypnoea
Cold clammy skin due to vasoconstriction
Dry face, dry mouth and goose skin appearance
(due to contraction of arrector pilorum).
Rapid thready pulse, hypotension
Oliguria
General measures
 APPLY DIRECT PRESSURE- This is to try and stop the
flow of blood and encourage a clot to form.
 APPLYA DRESSING - Applying a sterile non-fluffy
dressing covers the wound protecting it and preventing the
spread of infection.
Check that the dressing isn’t too tight and restricting circulation
 ELEVATION- Elevate the bleeding limb or area above ’ s
heart . This will reduce the amount of blood flow to the
wound.
 MONITOR – Periodically Monitor the Individual as they
may go into shock due to blood loss..
MECHANICAL METHODS
 PRESSURE
 Firm pressure should be applied over the bleeding
site using either fingers or gauze for at least 5 to 10
minutes.
 This would control most hemorrhages by
counteracting the hydrostatic pressure of the
bleeding vessel.
 HAEMOSTAT
 Application of haemostat at the bleeding point
helps in direct occlusion of the bleeding vessel
METHODS OF ACHIEVING HEMOSTASIS
SUTURES AND LIGATION
• Severed blood vessels may be tied with
ligatures.
A ligature replaces the hemostat as a
permanent method of effective
hemostasis.
• For large pulsatile artery, a trans –
fixation suture to prevent slipping is
indicated.
• Non – resorbable sutures such as silk and
polyethylene are used as they evoke less
tissue reaction.
SURGICEL / OXYCEL
 Oxidized cellulose polymer obtained by dissolving pure alphacellulose in an
alkaline solution.
 Absorbable hemostatic material is manufactured by controlled
oxidation of cellulose using nitrous dioxide.
 Cellulosic acid present in it has affinity for hemoglobin which leads to the
formation of artificial sticky gelatinous clot.
 Should be applied on the dry surface as the acid formed during the wetting
process inactivates the thrombin.
 Applied surgicel resorbs from the site in 4 to 8 weeks.
 Disadvantage is that the surgicel clot is not formed by normal physiological
mechanism.
SURGICEL FIBRILLAR:
 Modified surgicel or oxidised regenerated cellulose in
layers that can be adapted to irregular surfaces and
inaccessible areas.
 Complete resorption occurs in 2 weeks.
GELATINE SPONGE OR GELFOAM OR
SURGIFOAM:
 Formed from purified pork skin gelatin.
 Completely absorbable material.
 Has the capacity to absorb 45 times its weight in
blood.
 Resorbs completely in 4 to 6 weeks.
MICROFIBRILLAR COLLAGEN
 Collagen derived from bovine skin.
 Results in activation of platelet aggregation.
 Absorption time is 3 months.
FIBRIN GLUE
 Biological adhesive which contains thrombin,
fibrinogen, factor XIII, aprotinin.
 Thrombin converts fibrinogen to unstable fibrin
clot, factor XIII stabilizes the clot and aprotinin
prevents its degradation.
STYPTICS & ASTRINGENTS
 Precipitates protein & arrests bleeding.
 Commonly used styptics & astringents are Monsel’s solution containing ferric subsulfate &
tannic acid.
 Thrombin & gelatin sponge are now widely used.
ALGINIC ACID
 Placed over the bleeding sites, a protective film is formed over the bleeding site, this film
compresses the capillaries & stabilizes the blood clot.
NATURAL COLLAGEN SPONGE
 White sponge material, fully absorbable. It stimulates the platelet
 aggregation thereby enhancing hemostasis.
 Activates coagulation factors XI & XIII.
 Preferred in patients who are susceptible for hemorrhage after dental surgical procedures.
Adrenaline Tranexamic acid
FIBRIN SPONGE
Obtained from bovine material.
Applied on the bleeding site especially in post extraction socket.
Fully absorbed by the tissues within 4-6 weeks.
OSTENE
 New bone hemostatic agent, made of water-soluble alkylene oxide
copolymers.
 Showed no incidence of adverse response in the cortical defect site,
medullary cavity or the surrounding tissue.
BONE WAX
 Sterilized, non – absorbable mix of waxes.
 Consists of seven parts by weight of wax (white bees wax, paraffin wax &
an isopropyl ester of palmitic acid), two parts of olive oil and one part of
phenol.
 Indicated in cases of bleeding from the bone or from chipped edges of bone.
 Bone wax is softened with the fingers to desired consistency & then applied
over the bleeding site.
 Mechanism - Mechanical obstruction of the osseous cavity containing the
bleeding vessels.
Systemic Agents:
WHOLE BLOOD:
 Fresh whole blood refers to blood that is administered within 24
hours
 of its donation.
 Whole blood transfusion indicated when there is excessive blood
loss.
 Contains all factors for coagulation.
 Must be checked for HIV, hepatitis B, C viruses.
PLATELET RICH PLASMA:
 Platelets can be collected from donated whole blood.
 Platelet concentrates are viable for 3 days when stored at room
 temperature.
 Must be infused quickly via short i.v. tranfusion set.
 One unit raises platelet count by approx 7,000 to 10,000 cells per
cu mm.
FRESH FROZEN PLASMA:
 Unit of fresh frozen plasma is collected from one donor and
contains all coagulation factors.
 Stored at -30°C, should be infused within 2 hours once
defrosted.
CRYOPRECIPITATE:
 Stored at -30°C.
 Each bag is derived from single donor and is not treated to
inactivate viruses.
 Associated with a substantial risk of viral transmission.
THERMAL AGENTS
Heat achieves hemostasis by denaturation of proteins.
CAUTERY:
 Heat is transmitted from instrument by conduction directly to the
tissues.
 Electro – cautery has replaced direct heat application.
 Most widely used.
 Can be applied directly to bleeding point.
 Cautery point is touched to the hemostat, causing sealing of vessel
through action of heat.
 Dental burnisher like instrument can be directly heated over flame and
applied directly to the bleeding point.
Advantages:
 Permits any degree of hemorrhage control.
 Provides clear and improved view.
 Increases efficiency.
 Reduces chair side time.
 Effective and convenient way of controlling hemorrhage
Disadvantages:
 Tissue destruction producing burning smell and smoke during application
CRYOSURGERY:
 Extreme cooling has been used for hemostasis.
 Temperature ranging from -20°C to -180°C are used.
 Tissues, capillaries, small arterioles and venules undergo cryogenic necrosis.
 Acts by dehydration and denaturation of lipid molecules.
LASERS:
 Lasers usually result in bloodless surgery.
 Effectively coagulate the small blood vessels during cutting of tissues.
DRUGS &OTHER HAEMOSTATICS
Drugs used for haemostatic therapy can be classified as:
I. Agents acting locally
II. Transfusional agents such as specific coagulation factors
III. Non transfusional agents
AGENTS ACTING LOCALLY
These agents control oozing of blood from minute vessels but are not effective
in controlling bleeding from large vessels.
 Thrombin - obtained from bovine plasma.
 Thromboplastin powder
 Fibrin: Obtained from human plasma used in dehydrated form as sheets
When used in combination with a thrombin solution, it acts as a mechanical
barrier and holds thrombin in position over the bleeding area.
FIBRINOGEN: Fibrinogen. a sterile fraction from human plasma, is used for
restoring normal fibrinogen levels in haemorrhage Fibrinogen & thrombin
may be employed together for local haemostasis.
ANTIHAEMOPHILIC GLOBULIN (AHG) : Antihaemophilic globulin or
concentrate of factor VIII (AHG) is highly effective in the treatment of
classical haemophilia-A prepared by recombinant DNA technique.
COAGULATION FACTORS: Pure recombinant factor VIII, factor IX
and factor VII are available. Very expensive and associated with a greater
risk of inducing inhibitor formation (IgG antibodies for VIII), thus reducing
the efficacy of specific therapv.
FRESH FROZEN PLASMA: FFP is suitable for the treatment of most
coagulation disorders, since it contains all the clotting factors. Concentrate
of factor VIII (purified) and partially purified preparation containing factors
II, VII, IX and X are also available for specific deficiencies.
Laboratory Tests for Screening
 Bleeding time
 Clotting time
 Platelet count
 Prothrombin time
 Partial thromboplastin time
BLEEDING TIME (BT)
 Bleeding time – Measure of duration of bleeding
after injury.
 Usually there is linear relationship between
platelet count and bleeding time. Patients with
bleeding time more than 10 minutes have
increased risk of bleeding.
 Various methods of measuring bleeding time, e.g.
Ivy (2-9 min), Duke method (1-3 min) etc
PLATELET COUNT
 Normal platelet count is 1,50,000 to 4,50,000 per cubic millimetre of blood.
 When count becomes 50,000 to 1,00,000 there is mild prolongation of bleeding
time
 Patients with platelet count below 20,000 have spontaneous bleeding, which
may be intracranial or any other internal bleeding.
 Minor oral surgical procedure can be safely done, if platelet count is above
80,000 to 1,00,000/cubic millimeter of blood, if not patient will need
transfusion of platelet rich plasma.
PROTHROMBIN TIME (PT)
 Screens the extrinsic coagulation pathway (Factors V, VII and X) and factors
I, II and V.
 Normal PT is usually 12-14 second
 INR [international normalized ratio which is patient’s PT to control PT]
should be 1.0 to 1.5.
PARTIAL THROMBOPLASTIN TIME (PTT)
 Screens the intrinsic coagulation pathway and tests for the adequacy of
factors VIII, IX, X, XI, XII of intrinsic system and factors I, II, V of the
common pathway. It is prolonged in haemophiliacs.
Normal value: 20-35 sec.
NON-TRANSFUSIONAL AGENTS
Vitamin K: Vitamin K comprises three distinct fat soluble, naphthoquinone
compounds which participate in the biosynthesis of factors VII, IX and X .
Aprotinin: It Is a polypeptide enzyme which inhibits serine protease and thus
inhibits plasmin, kallikrein and trypsin activity thus It inhibiting fibrinolysis
Epsilon Amino Caproic Acid: Water soluble lysine analog which binds to the
lysine binding sites inhibits binding of plasmin to fibrin
Hemorrhage and its Management

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Hemorrhage and its Management

  • 2. introduction Prolonged or uncontrolled bleeding is often referred to as hemorrhage. Blood carries oxygen and nutrients to the tissues and is vital for body functions.  Any damage to the vasculature leads to the outflow of blood. Escape of blood from a blood vessel.
  • 3. Hemostasis Mechanism 1. VASCULAR PHASE 2. PLATELET PHASE 3. COAGULATION PHASE
  • 4.
  • 5. factors affecting HEMOSTASIS  Vessel Wall Integrity  Adequate Numbers of Platelets  Proper Functioning Platelets  Adequate Levels of Clotting Factors  Proper Function of Fibrinolytic Pathway
  • 6.
  • 7. CLASSIFICATION OF HEMORRHAGE 1. Depending on the SOURCE OF BLEEDING: i) External Hemorrhage: When bleeding is revealed and seen outside, e.g. epistaxis. ii) Internal Hemorrhage: Bleeding is concealed and not seen outside, e.g. intracranial hematoma. 2. Depending on the NATURE OF BLEEDING VESSEL: i) Arterial Hemorrhage: Bright red in color. Blood emitted as a jet with each heartbeat. ii) Venous Hemorrhage: Dark red in color. Blood flow is steady. iii) Capillary Hemorrhage: Bright red in color. Generalized ooze of blood instead of blood flow.
  • 8.
  • 9. 3. Depending upon TIME OF HEMORRHAGE: i) Primary Hemorrhage: Occurs at the time of trauma or surgery. ii) Reactionary Hemorrhage: Occurs within 24 hours of trauma or operation. iii) Secondary Hemorrhage: Occurs after 7 – 14 days of trauma oroperation. 4. Depending upon VOLUME OF BLOOD LOSS: i) Mild Hemorrhage: Blood loss ≤ 500 mL. ii) Moderate Hemorrhage: Blood loss 500 – 1000 mL. iii) Severe Hemorrhage: Blood loss ≥ 1 L. CLASSIFICATION OF HEMORRHAGE
  • 10. 5. Depending upon SPEED OF BLOOD LOSS: i) Acute Hemorrhage: Massive bleeding in short span of time. ii) Chronic Hemorrhage: Slow bleeding small in quantity for long time. 6. Depending upon PERCENTAGE OF BLOOD LOSS: i) Class I: Up to 15%. ii)Class II: Between 15 – 30%. iii) Class III: Between 30 – 40%. iv) Class IV: More than 40%.
  • 11. ETIOLOGY  Trauma.  Infections.  Congenital malformations.  Surgical (intraoperative/postoperative).  Due to systemic diseases (viral infection, scurvy, allergy).  Abnormalities in clotting factor (hemophilia A, multiple myeloma).  Abnormalities in platelets (leukemia, ITP, thrombocytosis, thrombocytopenia).
  • 12. Clinical features Pallor, thirsty, cyanosis Tachycardia, tachypnoea Cold clammy skin due to vasoconstriction Dry face, dry mouth and goose skin appearance (due to contraction of arrector pilorum). Rapid thready pulse, hypotension Oliguria
  • 13. General measures  APPLY DIRECT PRESSURE- This is to try and stop the flow of blood and encourage a clot to form.  APPLYA DRESSING - Applying a sterile non-fluffy dressing covers the wound protecting it and preventing the spread of infection. Check that the dressing isn’t too tight and restricting circulation  ELEVATION- Elevate the bleeding limb or area above ’ s heart . This will reduce the amount of blood flow to the wound.  MONITOR – Periodically Monitor the Individual as they may go into shock due to blood loss..
  • 14. MECHANICAL METHODS  PRESSURE  Firm pressure should be applied over the bleeding site using either fingers or gauze for at least 5 to 10 minutes.  This would control most hemorrhages by counteracting the hydrostatic pressure of the bleeding vessel.  HAEMOSTAT  Application of haemostat at the bleeding point helps in direct occlusion of the bleeding vessel METHODS OF ACHIEVING HEMOSTASIS
  • 15. SUTURES AND LIGATION • Severed blood vessels may be tied with ligatures. A ligature replaces the hemostat as a permanent method of effective hemostasis. • For large pulsatile artery, a trans – fixation suture to prevent slipping is indicated. • Non – resorbable sutures such as silk and polyethylene are used as they evoke less tissue reaction.
  • 16.
  • 17. SURGICEL / OXYCEL  Oxidized cellulose polymer obtained by dissolving pure alphacellulose in an alkaline solution.  Absorbable hemostatic material is manufactured by controlled oxidation of cellulose using nitrous dioxide.  Cellulosic acid present in it has affinity for hemoglobin which leads to the formation of artificial sticky gelatinous clot.  Should be applied on the dry surface as the acid formed during the wetting process inactivates the thrombin.  Applied surgicel resorbs from the site in 4 to 8 weeks.  Disadvantage is that the surgicel clot is not formed by normal physiological mechanism.
  • 18. SURGICEL FIBRILLAR:  Modified surgicel or oxidised regenerated cellulose in layers that can be adapted to irregular surfaces and inaccessible areas.  Complete resorption occurs in 2 weeks. GELATINE SPONGE OR GELFOAM OR SURGIFOAM:  Formed from purified pork skin gelatin.  Completely absorbable material.  Has the capacity to absorb 45 times its weight in blood.  Resorbs completely in 4 to 6 weeks.
  • 19. MICROFIBRILLAR COLLAGEN  Collagen derived from bovine skin.  Results in activation of platelet aggregation.  Absorption time is 3 months. FIBRIN GLUE  Biological adhesive which contains thrombin, fibrinogen, factor XIII, aprotinin.  Thrombin converts fibrinogen to unstable fibrin clot, factor XIII stabilizes the clot and aprotinin prevents its degradation.
  • 20. STYPTICS & ASTRINGENTS  Precipitates protein & arrests bleeding.  Commonly used styptics & astringents are Monsel’s solution containing ferric subsulfate & tannic acid.  Thrombin & gelatin sponge are now widely used. ALGINIC ACID  Placed over the bleeding sites, a protective film is formed over the bleeding site, this film compresses the capillaries & stabilizes the blood clot. NATURAL COLLAGEN SPONGE  White sponge material, fully absorbable. It stimulates the platelet  aggregation thereby enhancing hemostasis.  Activates coagulation factors XI & XIII.  Preferred in patients who are susceptible for hemorrhage after dental surgical procedures.
  • 21. Adrenaline Tranexamic acid FIBRIN SPONGE Obtained from bovine material. Applied on the bleeding site especially in post extraction socket. Fully absorbed by the tissues within 4-6 weeks.
  • 22. OSTENE  New bone hemostatic agent, made of water-soluble alkylene oxide copolymers.  Showed no incidence of adverse response in the cortical defect site, medullary cavity or the surrounding tissue. BONE WAX  Sterilized, non – absorbable mix of waxes.  Consists of seven parts by weight of wax (white bees wax, paraffin wax & an isopropyl ester of palmitic acid), two parts of olive oil and one part of phenol.  Indicated in cases of bleeding from the bone or from chipped edges of bone.  Bone wax is softened with the fingers to desired consistency & then applied over the bleeding site.  Mechanism - Mechanical obstruction of the osseous cavity containing the bleeding vessels.
  • 23. Systemic Agents: WHOLE BLOOD:  Fresh whole blood refers to blood that is administered within 24 hours  of its donation.  Whole blood transfusion indicated when there is excessive blood loss.  Contains all factors for coagulation.  Must be checked for HIV, hepatitis B, C viruses. PLATELET RICH PLASMA:  Platelets can be collected from donated whole blood.  Platelet concentrates are viable for 3 days when stored at room  temperature.  Must be infused quickly via short i.v. tranfusion set.  One unit raises platelet count by approx 7,000 to 10,000 cells per cu mm.
  • 24. FRESH FROZEN PLASMA:  Unit of fresh frozen plasma is collected from one donor and contains all coagulation factors.  Stored at -30°C, should be infused within 2 hours once defrosted. CRYOPRECIPITATE:  Stored at -30°C.  Each bag is derived from single donor and is not treated to inactivate viruses.  Associated with a substantial risk of viral transmission.
  • 25. THERMAL AGENTS Heat achieves hemostasis by denaturation of proteins. CAUTERY:  Heat is transmitted from instrument by conduction directly to the tissues.  Electro – cautery has replaced direct heat application.  Most widely used.  Can be applied directly to bleeding point.  Cautery point is touched to the hemostat, causing sealing of vessel through action of heat.  Dental burnisher like instrument can be directly heated over flame and applied directly to the bleeding point.
  • 26. Advantages:  Permits any degree of hemorrhage control.  Provides clear and improved view.  Increases efficiency.  Reduces chair side time.  Effective and convenient way of controlling hemorrhage Disadvantages:  Tissue destruction producing burning smell and smoke during application
  • 27. CRYOSURGERY:  Extreme cooling has been used for hemostasis.  Temperature ranging from -20°C to -180°C are used.  Tissues, capillaries, small arterioles and venules undergo cryogenic necrosis.  Acts by dehydration and denaturation of lipid molecules. LASERS:  Lasers usually result in bloodless surgery.  Effectively coagulate the small blood vessels during cutting of tissues.
  • 28. DRUGS &OTHER HAEMOSTATICS Drugs used for haemostatic therapy can be classified as: I. Agents acting locally II. Transfusional agents such as specific coagulation factors III. Non transfusional agents
  • 29. AGENTS ACTING LOCALLY These agents control oozing of blood from minute vessels but are not effective in controlling bleeding from large vessels.  Thrombin - obtained from bovine plasma.  Thromboplastin powder  Fibrin: Obtained from human plasma used in dehydrated form as sheets When used in combination with a thrombin solution, it acts as a mechanical barrier and holds thrombin in position over the bleeding area.
  • 30. FIBRINOGEN: Fibrinogen. a sterile fraction from human plasma, is used for restoring normal fibrinogen levels in haemorrhage Fibrinogen & thrombin may be employed together for local haemostasis. ANTIHAEMOPHILIC GLOBULIN (AHG) : Antihaemophilic globulin or concentrate of factor VIII (AHG) is highly effective in the treatment of classical haemophilia-A prepared by recombinant DNA technique.
  • 31. COAGULATION FACTORS: Pure recombinant factor VIII, factor IX and factor VII are available. Very expensive and associated with a greater risk of inducing inhibitor formation (IgG antibodies for VIII), thus reducing the efficacy of specific therapv. FRESH FROZEN PLASMA: FFP is suitable for the treatment of most coagulation disorders, since it contains all the clotting factors. Concentrate of factor VIII (purified) and partially purified preparation containing factors II, VII, IX and X are also available for specific deficiencies.
  • 32. Laboratory Tests for Screening  Bleeding time  Clotting time  Platelet count  Prothrombin time  Partial thromboplastin time
  • 33. BLEEDING TIME (BT)  Bleeding time – Measure of duration of bleeding after injury.  Usually there is linear relationship between platelet count and bleeding time. Patients with bleeding time more than 10 minutes have increased risk of bleeding.  Various methods of measuring bleeding time, e.g. Ivy (2-9 min), Duke method (1-3 min) etc
  • 34. PLATELET COUNT  Normal platelet count is 1,50,000 to 4,50,000 per cubic millimetre of blood.  When count becomes 50,000 to 1,00,000 there is mild prolongation of bleeding time  Patients with platelet count below 20,000 have spontaneous bleeding, which may be intracranial or any other internal bleeding.  Minor oral surgical procedure can be safely done, if platelet count is above 80,000 to 1,00,000/cubic millimeter of blood, if not patient will need transfusion of platelet rich plasma.
  • 35. PROTHROMBIN TIME (PT)  Screens the extrinsic coagulation pathway (Factors V, VII and X) and factors I, II and V.  Normal PT is usually 12-14 second  INR [international normalized ratio which is patient’s PT to control PT] should be 1.0 to 1.5. PARTIAL THROMBOPLASTIN TIME (PTT)  Screens the intrinsic coagulation pathway and tests for the adequacy of factors VIII, IX, X, XI, XII of intrinsic system and factors I, II, V of the common pathway. It is prolonged in haemophiliacs. Normal value: 20-35 sec.
  • 36. NON-TRANSFUSIONAL AGENTS Vitamin K: Vitamin K comprises three distinct fat soluble, naphthoquinone compounds which participate in the biosynthesis of factors VII, IX and X . Aprotinin: It Is a polypeptide enzyme which inhibits serine protease and thus inhibits plasmin, kallikrein and trypsin activity thus It inhibiting fibrinolysis Epsilon Amino Caproic Acid: Water soluble lysine analog which binds to the lysine binding sites inhibits binding of plasmin to fibrin