4. Bleeding
• Bleeding disorder is defined as inability to form a
normal clot after an exposure to trauma, injury,
surgery or menstruation which leads to extensive
bleeding and might be a life threatening condition.
• The treatment of bleeding disorders depends on the
type and severity of the bleeding.
• Anti-hemorrhagic agents are used to stop bleeding;
they are also known as hemostatic agents.
5. Stopping Bleeding
• External bleeding is usually stopped by
– Manual pressure
– Cotton-gauze pressure pack
– Suturing
– Cold compress
– Use of Cautery (internal bleeding)
Control of bleeding may be aided by local
hemostatics/ styptics- substances used to stop
bleeding from a local and approachable site
6. Coagulants
• The substances which promote coagulation, and are
indicated in hemorrhagic states.
• Clotting factor deficiency states- best treated with
fresh whole blood or plasma.
• Drugs used for coagulation purpose:
• Vitamin K1– Phytomenadione (Plants)
• Vitamin K2 –Menadione (GI bacteria)
• Tranexamic acid
• Ethamsylate
• Desmopressin
7. Hemostatic agents
Hemostatic agents used in medicine are either:
Locally-acting hemostatic agents (styptics): They
work by causing vasoconstriction or promoting platelet
aggregation
Systemic drugs: They work by inhibiting fibrinolysis or
promoting coagulation. These include
Vitamin K,
Antifibrinolytics (e.g., aminocaproic acid ),
Fibrinogen, and
Blood coagulation factors
8. Styptics
Styptics are a specific type of hemostatic
agents that work by contracting tissue to
seal injured blood vessels.
They are particularly useful in oozing
surfaces:
Tooth socket,
abrasions, etc.
9. Styptics
• Fibrin (Prepared from human plasma and dried as
sheet or foam)
• Gelatin foam (Porcine or bovine gelatin)
• Oxidized cellulose (Strips which can be cut and
placed in the wound)
• Thrombin (Obtained from bovine plasma)
• Adrenaline applied locally
• Astringents like tannic acid, Ferric Chloride, Ferric
Sulfate (concentrated forms)
10. Styptics
• Styptics like fibrin, gelatin foam and oxidized
cellulose provide a meshwork for activation of
clotting mechanisms and checks bleeding.
• Left in situ
• Get absorbed in 1-4 weeks times without causing
allergic reactions
• Thrombin may be applied as dry powder or freshly
prepared solution to the bleeding surface in
haemophiliacs.
11. Fibrin
• Obtained from human plasma
• Dehydrated form as sheets- cut to size
• When used in combination with thrombin solution,
acts as a mechanical barrier and holds thrombin in
position over the bleeding area.
12. Gelatin foam/sponge
• Porous pressed form of gelatin sponge
• Used in conjunction with thrombin to control oozing
of blood from surface wounds.
• Usually moistened with sterile, isotonic saline before
use
• Completely absorbed in 1- 4 weeks, when left in
place after suturing the wounds
• Available in different shapes and sizes
13. Oxidized cellulose
• Surgical gauze treated with nitrogen dioxide
• Promotes clotting by a reaction between cellulosic
acid and hemoglobin
• When wet with tissue fluids, oxidized cellulose
becomes sticky, gummy and offers mechanical
blockade which simulates an artificial clot over the
wound surface.
• Absorbed completely within 2-10 days
• Interferes with bone regeneration
14. Thrombin
• Obtained from bovine plasma
• Stable in dried powder form @ 2-8oC.
• Inactive below pH 5.
• Use restricted to local application in oozing of blood
• Also used, mixed with plasma, to anchor skin grafts
in place
15. Styptics- Vasoconstrictors
• Vasoconstrictors like 0.1% Adr solution may be
soaked in sterile cotton-gauze and packed in:
– bleeding tooth socket or
– nose in case of epistaxis
• to check bleeding when spontaneous
vasoconstriction is inadequate.
– Epinephrine (1:200,000/1:100,000/1:50,000),
– Levonordefrine (1:20,000) and
– Norepinephrine (1:30,000)
19. Deficiency
– Newborns – higher risk
• Rare in adults (Biliary obstruction, malabsorption)
– Patients with liver damage or disease
– Those with eating disorders
– Those taking vitamin K antagonists (warfarin)
–
• Signs/symptoms
– Heavy menstrual bleeding, anemia, nose bleeds,
osteoporosis, coronary heart disease
– Gum bleeding, GI bleeding, blood in urine
– In infants - intracranial hemorrhage
20. Physiological Effects of Vitamin K
Vitamin K serves as an essential
cofactor for a carboxylase that
catalyzes carboxylation of
glutamic acid residues on
vitamin K-dependent proteins.
These proteins are involved in:
1) Coagulation
2) Bone Mineralization
3) Cell growth
21. Biosynthesis of GluGla
Vitamin K-dependent
carboxylation of
glutamic acid (Glu)
residues forms
γ-carboxyglutamic
acid (Gla).
Gla residues aid in the
chelation of calcium
ions and ensure these
clotting proteins can
bind to platelets and
endothelial cells.
+ CO2
22. Hemorrhagic Disease of Newborns
Newborns are prone to vitamin K deficiency because…
1. Vitamin K pass by simple diffusion across placental barrier (less)
2. Prothrombin synthesis in the liver is an immature process in
newborns, especially when born premature.
3. The neonatal gut is sterile, lacks the bacteria that is necessary in
menaquinone synthesis.
4. Breast milk is not a good source of vitamin K
• Results in a haemorrhagic disease called vitamin K deficiency bleeding
(VKDB) or Hemorrhagic disease of newborns (HDN)
• HDN- often fatal condition- diffuse hemorrhage of normal infant
• Incidence 2.5-17 per 1000s of live births not given Vit K prophylactically
• IM administration 0.5-1mg within first 6 hours after birth or orally over
first 4 weeks after birth.
23. Vitamin K Dependent Coagulation
• Certain clotting factors/proteins require calcium to bind for
activation
• Calcium can only bind after gamma carboxylation of specific
glutamic acid residues in these proteins
• The reduced form of vitamin K2 (vitamin KH2) acts as a cofactor
for this carboxylation reaction.
• These proteins are known as “Vitamin K dependent” proteins
25. Recycling of Vitamin K
• Very minimal body stores
• Must have regular dietary intake
• Recycles so that the same vitamin K can be cycled and
re-used many times (decreasing need in dietary intake)
• Warfarin -- Vitamin K antagonist
• Warfarin blocks vitamin K recycling and activation (by
inhibiting 2 reductase) therefore, carboxylation of
glutamic acid cannot occur at a normal rate
• This decreases blood coagulation.
– anticoagulant.
26. Warfarin Blocks 2 Pathways
(1) Blocks Quinone
Reductase
Vitamin K’s
activation to
Vitamin K
hydroquinone
(2) Blocks Vitamin K-epoxide
reductase
Vitamin K (epoxide)
recycling to Vitamin K
27. Clinical Uses
• In the prophylaxis and treatment of bleeding due to
deficiency of clotting factors.
1. Dietary deficiency
2. Prolonged antimicrobial therapy
3. Obstructive jaundice or malabsorption syndromes
(sprue, regional ileitis, steatorrhoea, etc.)
4. Liver disease (cirrhosis, viral hepatitis)
5. Newborns-HDN
6. Overdose of oral anticoagulants
7. Prolonged high dose salicylate therapy causes
hypoprothrombinemia; Vit K should be given
prophylactically.
28. Vitamin K – A/E
– Not common except with over-supplementation
– Phylloquinone and menaquinone are relatively nontoxic
• Jaundice; brain damage
– Menadione toxic to skin and respiratory tract in high
doses
– Reports of hemolysis in G6PD deficiency noted
– Rapid i.v. injection of emulsified vit K produces flushing,
breathlessness, a sense of constriction in the chest, fall in
BP; few deaths are on record.
– It is probably due to emulsion form of the preparation.
29. Aminocaproic acid
It is water soluble analogue
of aminoacid lysine.
Oral administration
• MOA
They occupy the lysine binding sites on plasminogen
Results in inhibition of fibrin binding to plasminogen
Activation of plasminogen to plasmin is inhibited
Impaired fibrolysis; de-stabilization of clot
30. Aminocaproic acid- Uses
Useful in preventing hyperplasminemic bleeding state
following damage to tissue rich in plasminogen activator.
Major trauma with risk of bleeding
Upper GI bleeding
Primary menorrhagia
Prostatic surgery
Bleeding following dental extraction (coagulation
disorder)
Bleeding associated with thrombocytopenia and PPH
32. Aminocaproic acid- Dosing
Half life: 2 hrs
Loading dose:
• Given in a dose of 100 mg/kg up to 10 gm, and 50
mg/kg up to 6 gm 6 hrly for 2-3 days.
• Dose should not exceed 30 gm in 24 hrs.
• Contraindicated in patients with subarachnoid
bleeding because it may induce vasospasm and
ischemic stroke.
33. Tranexamic Acid
• Lysine derivative
• 10x more potent than Aminocaproic acid
• Longer DOA , half life 3 hrs
• Dose: 1-1.5 gm, 3-4 times daily
• Uses like aminocaproic acid
• A/Es: nausea, diarrhoea and hypotension
• Contraindicated in patients with subarachnoid
bleeding because it may induce vasospasm and
ischemic stroke.
34. Desmopressin
• Analogue of arginine vasopressin
• IV or SC
• Increases for a short time plasma concentration of
– factor VIII in hemophiliacs and (DOC in Hemophilia Type A)
– von Willebrand factor (adhesive factor) in VW Disease- Type I
– Shortens or normalizes bleeding time in patients with
congenital defects of platelet function.
– Useful in acquired bleeding disorders-like uremia following
drugs like aspirin
– Used in acute variceal bleeding
– A/E: headache, water retention, hyponatremia
