3. Haemostasis (arrest of blood loss) ---finely regulated dynamic
process of maintaining fluidity of the blood, repairing vascular injury,
and limiting blood loss while avoiding vessel occlusion (thrombosis)
and inadequate perfusion of vital organs.
Either extreme—excessive bleeding or thrombosis—represents a
breakdown of the hemostatic mechanism.
Can be genetic or acquired.
It involves a complex interaction between the injured vessel wall,
platelets and coagulation factors.
4. To arrest bleeding process.
Differentiate between bleeding due to platelet disorders(e.g von
Willebrand ds) and clotting factor disorders(e.g hemophillia –A).
To know the thrombus type.
Treatment of the disorder accordingly.
7. Two in vitro tests ‘activated partial thromboplastin time’ (aPTT) and
‘prothrombin time’ (PT) are employed for testing integrity of the
intrinsic, extrinsic and common pathways of the coagulation
cascade.
8. AGENTS ACTING LOCALLY TRANFUSIONAL AGENTS NON TRANSFUSIONAL
(STYPTICS)
THROMBIN, VIT K(K1,K2,K3)
FAC VIII AND 1X (AHG) ETHAMSYLATE
THROMBOPLASTIN FIBRINOGEN VIT C ,RUTIN
FIBRIN PLASMA /WHOLEBLOOD APROTININ
GEL FOAM RECOMBINANT FACTOR VIIA DESMOPRESSIN
OXIDIZED CELLULOSE ORPHAN DRUGS CONJUGATED ESTROGEN
VASOCONSTRICTORS SCLEROSING AGENTS
ASTRINGENTS
AVITENE
9. Substances used to stop bleeding from a local and approachable site.
e.g. tooth sockets, nasal bleeding, abrasions.
Provide meshwork that activates clotting mechanism and checks
bleeding.
1.THROMBIN
obtained from bovine plasma.
Used as dry powder or freshly prepared solution to bleeding surfaces in
hemophiliacs.
2.THROMBOPLASTIN
powder prepared from lung or brain tissue of rabbit.
Used for determination of prothrombin time and as local hemostatic in
surgery.
3.FIBRIN
Human plasma derivative.
Used in sheet form on bleeding surface.
Used along with thrombin ----- mechanical barrier.
10. 4.GELFOAM
pressed form of gelatin sponge.
Used along with thrombin.
5.OXIDIZED CELLULOSE(OXYCEL)
Surgical gauze treated with nitrogen dioxide.
Promotes clotting by a reaction between Hb and cellulosic acid.
6. MICROFIBRILLAR COLLAGEN HEMOSTASIS (AVITENE)
From bovine collagen.
Used in capillary bleeding cases.
7.VASOCONSTRICTORS
0.1% Adr solution may be soaked in sterile cotton gauze and packed
in the bleeding tooth socket or nose in case of epistaxis to check
bleeding when spontaneous vasoconstriction is inadequate.
8. ASTRINGENTS such as tannic acid or metallic salts are occasionally
applied for bleeding gums, bleeding piles, etc.
11. 1. FIBRINOGEN:
From human plasma.
Used in acute afibrinogenemia, hemophilia.
Can be used with thrombin for local hemostasis.
Dose :FIBRINAL 0.5 g/bottle for i.v. infusion.
2. ANTIHEMOPHILIC GLOBULIN(AHG)
Hemophilia A (VIII) and Hemophilia B(IX) most common hereditary
hemorrhagic states .
ELOCTATE is a factor VIII-Fc domain conjugate that prolongs the
factor VIII half-life and allows twice-weekly dosing in many cases.
HUMATE-P a factor VIII concentrate that is approved by the FDA for
the treatment of bleeding associated with von Willebrand disease.
Fac VIII conc has a t1/2 of 12hrs in hem A pts. Dose: 15-60U/kg.
12. In Hem B –
Fresh frozen plasma is indicated.
IDELVION is a factor IX-albumin conjugate with a half-life of 100 hours is
FDA-approved for prophylaxis or treatment of bleeding in hemophilia B
patients, offering the possibility of once-weekly dosing .
VONICOG ALFA is a recombinant von Willebrand factor product approved
for treatment and control of bleeding in adults with von Willebrand disease.
A four-factor plasma replacement preparation containing vitamin K–
dependent factors II VII, IX, and X (4F PCC, Kcentra) is available for rapid
reversal of warfarin in bleeding patients
3.PLASMA OR WHOLE BLOOD:
FFP is suitable in most clotting disorders.
Whole blood not an ideal replacement as max chances of tranfusion
reactions occur.
13. 4.RECOMBINANT FACTOR VIIa:
approved for treatment of inherited or acquired
hemophilia A or B.
treatment of bleeding associated with invasive procedures
in congenital or acquired hemophilia, or factor VII
deficiency.
Factor VIIa initiates activation of the clotting pathway by
activating factor IX and factor X in association with tissue
factor.
The drug is given by bolus injection.
Off-label indications: bleeding with trauma,
surgery,intracerebral hemorrhage, and warfarin toxicity.
S/E:Increased thrombotic events.
14. ORPHAN DRUGS FOR TREATMENT OF RARE HEREDITARY
COAGULATION DISORDERS
Recombinant factor XIII A-subunit
Factor X concentrate
Protein C concentrate ----------NOW WITHDRAWN.
15. 1.VIT-K
It is a fat-soluble dietary principle required for the synthesis of
clotting factor II, VII, IX and X.
SOURCES: Green leafy vegetables, such as cabbage ,spinach and
liver, cheese, etc.
16. TYPE SOURCE SIDE CHAIN USES
VIT K1 DIETARY SOURCES PHYTYL
(PHYTONADIONE)
NEWBORNS
VIT K2 INTESTINE PRENYL
(MENAQUINONE)
BONE
MINERALISATION
VARICOSE VEINS
VIT K3 SYNTHETIC NO
MENADIONE
NO
17.
18. DAILY REQUIREMENT
It is uncertain, because a variable amount of menaquinone (vit K2)
produced by colonic bacteria becomes available.
for adults: 50–100 μg/day.(appox)
PK PARAMETERS:
Fat-soluble forms of vit K are absorbed from the intestine via lymph
and require bile salts for absorption, while water-soluble forms are
absorbed directly into portal blood.
No significant stores in the body.
Metabolized in liver
Excreted in bile and urine.
DEFICIENCY
liver disease, obstructive jaundice, malabsorption, long-term
antimicrobial therapy which alters intestinal flora.
most important manifestation ------bleeding
19. The only use of vit K is in prophylaxis and treatment of bleeding due to
deficiency of clotting factors in the following situations:
(a) Dietary deficiency: very rare in adults. However, when it occurs 5–10
mg/day oral or parenteral vit K rapidly corrects the defects.
(b) Prolonged antimicrobial therapy: treat in the same way as dietary
deficiency of vit K.
(c) Obstructive jaundice or malabsorption syndromes :(sprue, regional
ileitis, steatorrhea, etc.): vit K 10 mg i.m./day, or orally along with bile salts.
20. (d) Liver disease (cirrhosis, viral hepatitis): poor response to vit K.
Because of hepatocellular damage, synthesis of clotting factors is
inadequate despite the presence of vit K.
It may be of some use if its absorption had been affected due to lack of bile
salts.
(e) Newborns:
All newborns have low levels of prothrombin and other clotting
factors.
Vit K1 1 mg i.m. soon after birth has been recommended routinely..
Menadione (K3) should not be used for this purpose .
21. f) Overdose of oral anticoagulants:
This is the most important indication of vit K.
Phytonadione(K1) is the preparation of choice.
Avoid high doses.
Severe: 10 mg i.m. followed by 5 mg 4 hourly; bleeding generally stops in 6–
12 hours, but normal levels of coagulation factors are restored only after 24 hr.
This dose of vit K will block anticoagulant action for 7–10 days.
Moderate: 10 mg i.m. followed by 5 mg once or twice according to response.
Mild: Just omit a few doses of the anticoagulant
(g) Prolonged high dose salicylate therapy causes
hypoprothrombinemia:
• vit K should be given prophylactically.
• If bleeding occurs—treat as for oral anticoagulants.
22. Adverse effects of vit K:
VIT K1 : Phytonadione injected i.m. or given orally hardly produces
any adverse effect.
• Allergic reactions are rare.
• Severe anaphylactoid reactions can occur on i.v. injection of
emulsified formulation; this route should not be used.
VIT K3:
Menadione and its water-soluble derivatives can cause haemolysis in
a dose-dependent manner.
Patients with G-6-P deficiency and neonates are especially
susceptible.
23. 2. ETHAMSYLATE:
It reduces capillary bleeding when platelets are adequate
,probably corrects abnormalities of platelet adhesion, but does not
stabilize fibrin (not an anti fibrinolytic).
USE: prevention and treatment of capillary bleeding in menorrhagia,
after abortion, PPH, epistaxis, malena, hematuria and after tooth
extraction, but efficacy is unsubstantiated.
Side effects : nausea, rash, headache
DOSE: 250–500 mg TDS oral/i.v.; ETHAMSYL
24. 3. VITAMIN C AND RUTIN:
Vit C effective only in bleeding due to scurvy.
Rutin
plant glycoside claimed to reduce capillary bleeding.
It has been used in a dose of 60 mg oral BD– TDS along with vit C which is
believed to facilitate its action.
Its efficacy is uncertain.
CADISPER-C 60 mg tab.
4.APROTININ:
A polypeptide.
Was used in cardiac cases.
Withdrawn .
5. DESMOPRESSIN :
It releases factor VIII and von Willebrand’s factor from vascular endothelium
and checks bleeding in hemophilia and von Willebrand's disease .
No role in hem B.
25. 6. CONJUGATED ESTROGENS:
Given i.v –0.6mg/kg/day ---improves platelet function---decreases
bleeding time.
7. SCLEROSING AGENTS
These are irritants, cause inflammation, coagulation and ultimately
fibrosis, when injected into hemorrhoids (piles) or varicose vein mass.
They are used only for local injection.
a. Sod. tetradecyl sulfate (3% with benzyl alcohol 2%):
0.5–2 ml at each site. SETROL 2 ml inj.
b. Polidocanol (3% inj): 2 ml; ASKLEROL 2 ml inj.