1

25 Trillion RBCs most abundant cells in the body Total body cell counts to 100 trillion. All the blood in the circulation traverses the entire circuit of the circulation an avera e of once each minute !hen the body is at rest" and as many as si# times each minute !hen a $erson becomes e#tremely active. The avera e blood volume of adults is about %& of body !ei ht" or about 5 liters. About '0& of blood is $lasma and (0& is RBCs. Hemorrhage : The esca$e of blood from the vessels or bleedin . Classification : a) Accordin to si*e i. ii. iii. iv. tissue b) Accordin to ty$es 1. 2. co$ious flo!. 3. oo*e. (. 5. '. +rimary hemorrha e 4econdary hemorrha e Reactionary hemorrha e Ca$illary hemorrha e . Bri ht red" often ra$id Arterial hemorrha e . Reco ni*ed as bri ht red blood" s$urtin as a /et !hich rises and falls in time !ith $ulse. 0enous hemorrha e . 1ar2 red blood" study +etechias $in $oint +ur$hra u$ to 1 cm ,cehymosis lar er -amatoma massive accumulation of blood !ithin a

Hemostasis and blood coagulation:

The term hemostasis means $revention of blood loss. 5henever a vessel is severed or ru$tured" hemostasis is achieved by several mechanisms. 1) 0ascular s$asm 2) 6ormation of $latelet $lu 3) formation of a blood clot as a result of blood coa ulation () eventual ro!th of fibrous tissue into the blood clot to close the hole in the vessel $ermanently. 1) Vascular constriction: The trauma to the vessel !all causes the vessel to contract7 this instantaneously reduce the flo! of blood from the vessel ru$ture. The contraction results from nervous refle#es" local humoral factors from the traumati*ed tissues and blood $latelets. 2) Formation of platelet plug : 8any very small vascular holes do develo$ 9thousands) thou ht the body each day it is often sealed by $latelet $lu rather than by a blood clot. +latelet re$air of vascular o$enin s is based on several im$ortant functions of the $latelet it self. 5hen $latelets come in contact !ith a dama ed vascular surface" such as colla en fibers in the vascular !all" the $latelets themselves immediately chan e their characteristics drastically. They be in to s!ell" they assume irre ular forms !ith numerous irradiatin $seudo$ods $rotrudin from their surfaces7 their contractile $roteins contract forcefully and cause the release of ranules that contain multi$le active factors. They become stic2y so that they adhere to colla en in the tissue and to a $rotein called von !illebrand factor that s$reads throu h the $lasma7 they secrete lar e :uantities of A1+7 and their en*ymes form thrombo#ane A2. The A1+ and thrombo#ane act on the nearby $latelets to activate them as !ell and the stic2ness of these additional

$latelets cause them to adhere to the ori inally activated $latelets. Therefore" at the site of any rent in a blood vessel !all" the dama ed vascular !all or e#travascular tissues. ,licit activation of successively increasin numbers of $latelets that themselves attract more and more additional $latelets" thus formin $latelet $lu . ;n the subse:uent $rocess of blood coa ulation" fibrin threads form" these attach ti htly to the $latelets" thus constructin a unyieldin $lu . ;f there is a lar e hole a blood clot in addition to the $latelet $lu is re:uired to sto$ bleedin . 3) Blood coagulation in the ruptured vessel: The third mechanism for hemostasis is formation of the blood clot. The colt be ins to develo$ in 15 to 20 seconds if the trauma to the vascular !all has been severe and in 1 to 2 minutes if the trauma has been minor. Activator substances from" traumati*ed vascular !all" from $latelets and from blood $roteins adherin to the traumati*ed vascular !all initiate the clottin $rocess. Mechanism of blood coagulation: 8ore than 50 im$ortant substances that affect blood coa ulation have been found n the blood and in the tissues. Clotting factors in blood and their s non ms: 6actor ; . 6ibrino en. 6actor ;; . +rothrombin. 6actor ;;; . Tissue thrombo$lastin or tissue factor. 6actor ;0 . Calcium. 6actor 0 . +roacceleria or labile factor 6actor 0; . 4erum $rothrombin conversion accelerator or $ro convertin or stable factor 6actor 0;; . Antihemo$hilic factor 9A-6) or antihemo$hilic factor A.

6actor 0;;; . +lasma thrombo$lstin com$onent 9+TC) or christmas factor or antihemo$hilic factor B. 6actor ;< . 4tuart factor 6actor < . +lasma thrombo$lastin anticedent 9+TA) or antihemo$hilic factor C. 6actor <; . -a eman factor. 6actor <;; . 6ibrin stabili*in factor. 6actor <;;; . 6letcher factor. 6actor <;0 . -i h molecular !ei ht 2inino en. 6actor <0 . +latelets. a) 4ome that $romote coa ulation called $rocoa ulants. b) =thers that inhibit coa ulation called anticoa ulants. 5hether blood !ill coa ulate de$ends on the balance bet!een these t!o rou$ of substances. ;n the blood stream the anticoa ulants normally $redominate" so that blood does not coa ulate !hile it is circulatin in the blood vessels. But !hen a vessel is ru$tured" $rocoa ulants in the area of the tissue dama e become >activated? and override the anticoa ulants and then a clot does develo$. ;n the field of blood coa ulation it is acce$ted fact that clottin ta2es $lace in three essential ste$s" they are 1. ;n res$onse to ru$ture of the vessel or dama e to the blood itself" a com$le# cascade of chemical reactions occur in the blood involvin more than a do*en blood coa ulation factors. The net result is formation of a com$le# of activated substances collectively called $rothrombin activator. 2. The $rothrombin activator cataly*es the conversion of $rothrombin in to thrombin.

3. The thrombin acts as an en*yme to convert fibrino en in to fibrin fibers that enmesh $latelets" blood cells and $lasma to form the clot.

1) !nitiation of coagulation : formation of prothrombin activator : 8echanism that initiate the clottin in first $lace" are" set into $lay by a) Trauma to the vascular !all and ad/acent tissues. b) Trauma to the blood or c) Contact of blood !ith dama ed endothelial cells or !ith colla en and other tissue elements outside the blood vessel. ;n each instance this leads to the formation of $rothrombin activator" !hich then causes $rothrombin conversion to thrombin and all subse:uent clottin ste$s. +rothrombin is a $lasma $rotein an al$ha2 lobulin. ;t is $resent in normal $lasma in a concentration of about 15 m @dl. ;t is a unstable $rotein that can s$lit easily into smaller com$ounds" one of !hich is thrombin. +rothrombin is formed continually by the liver" vit. A is re:uired by liver for normal formation of $rothrombin. ,ither lac2 of vit. A or R the $resence of liver disease that $revents normal $rothrmobin formation can cause the $rothrmbin level so lo! that a bleedin tendency results. +rothombin activator is enerally considered to be formed in t!o !ays" althou h" in reality" the t!o !ays interact constantly !ith each other" 1) By the e#trinsic $ath!ay that be ins !ith trauma to the vascular !all and surroundin tissues and 2) By intrinsic $ath!ay that be ins is blood itself.

'

1) "#trinsic path$a for initiating blood clotting : ; ;; T;44B, TRAB8A

T;44B, 6ACT=R 0;; 0;;a < CaCC Activated < CaCC

+latelets $hos$holi$ids ;;; +rothrmobin

+rothrmobin activator Thrmobin CaCC

a) %elease of tissue factor : Traumati*ed tissue releases a com$le# of several factors called tissue factor" that functions mainly as a $roteolytic en*yme. b) &ctivation of factor ' : The tissue factor further com$le#es !ith blood coa ulation factor 0;; and in the $resence of calcium ions" acts en*ymatically on factor < to form activated factor < 9<a). c) "ffect of activated factor ' ('a) to form prothrombin activator :

The

activated factor

< combines

immediately

!ith tissue

$hos$holi$ids that are $art of tissue factor or 5-D additional $hos$holi$ids released from $latelets" as !ell as !ith factor 0 to form com$le# called $rothrombin activator. 5ithin a fe! seconds" in the $resence of calcium ions this s$lits $rothrombin to form thrombin. =nce the clottin $rocess is be un activated factor 0 becomes a additional stron accelerator of $rothrombin activation. This is 2no!n as $ositive feed bac2 effect of thrombin in acceleratin the entire $rocess. !ntrinsic path$a for initiating clotting : The second mechanism for initiatin the formation of $rorthmbin activator and therefore for initiatin be ins !ith trauma to the blood itself or e#$osure of blood to colla en in a traumati*ed vascular !all and continues throu h the follo!in reactions" Blood trauma or contact !ith colla en <;; Activated <;; 9-85 2ino en" $re2alli2erin) <; Activated <; CaCC ;< 0;;; Thrombin < Activated ;< CaCC Activated < CaCC

+latelet $hos$hali$id and factor ;;;

+rothrombin activator +rothrombin CaCC Thrombin

a) &ctivation of factor '!! and release of platelet phospholipids : Trauma to the blood or e#$osure of the blood or e#$osure of the blood to vascular !all colla en alters t!o im$ortant clottin factors in the bloodEfactor <;; and the $latelets. 5hen factor <;; is disturbed it ets converted in to $roteolyte en*yme called activated factor <;;. 4imultaneously the blood trauma also dama es the $latelets" either because of adherence to colla en or to a !ettable surface and this releases $latelet $hos$hali$id containin li$o$rotein called $latelet factor 3 !hich also $lays a role in subse:uent clottin reactions. b) &ctivation of factor '! : The activated factor <;; acts en*ymatically on factor <; to activate this as !ell" !hich is the second ste$ in the intrinsic $ath!ay. This reaction also re:uires -85 2inino en and it is accelerated by $re2alli2rein. c) &ctivation of factor !' b activated factor '! : The activated factor <; then acts en*ymatically on factor ;< to activate this factor also. d) &ctivation of factor ' ) role of factor V!!! : The activated factor ;<" actin in concert !ith factor 0;;; and !ith the $latelet $hos$holi$ids and factor 3 from the traumati*ed $latelets activates factor <. it is clear that !hen either factor 0;;; or $latelets are in short su$$ly this ste$ is deficient. 6actor 0;;; is the factor that is missin in the $erson !ho has classic hemo$hilia. +latelets are the clottin factor that is lac2in in the bleedin disease called thrombocyto$enia. e) &ction of activated factor ' to from prothrombin activator ) role of factor V :

This ste$ in the intrinsic $ath!ay is the same as the last ste$ of the e#trinsic $ath!ay i.e. activated factor < combines !ith factor 0 and $latelet or tissue $hos$holi$ids to from the com$le# called $rothrombin activator. The $rothrombin activator initiates !ithin seconds the cleava e of $rothrombin to from thrombin" there by settin clottin $rocess. %ole of calcium ions in to intrinsic and e#trinsic path$a : ,#ce$t for first t!o ste$s in the intrinsic $ath!ay calcium is re:uired for all the reactions" therefore in the absence of calcium blood clottin !ill not occur. ;n livin $erson calcium ion concentration rarely falls lo! enou h to affect si nificantly 2inetics of clottin . 5hen blood is removed from body" it can be $revented from clottin by reducin calcium ion concentration belo! threshold level for clottin either by deioni*in or by a. Reactin !ith substances li2e citrate ions. b. +reci$itatin calcium !ith substances li2e o#alate ions. !nteraction bet$een intrinsic and e#trinsic path$a : Clottin is initiated simultaneously by both $ath!ays. The tissue factor initiates e#trinsic $ath!ay" factor <;; and $latelets contact !ith colla en initiates intrinsic $ath!ay. Another im$ortant interaction bet!een the t!o systems is caused by $roteolytic effects of thrombin to activate en*ymes in the intrinsic $ath!ay. ;ntravascular clottin intrinsic $ath!ay. , . Anti en antibody reaction. 1ru s or debris that enter circulation. ;n im$ortant difference bet!een the 2 $ath!ays is that the e#trinsic $ath!ay can be e#$losive in nature" once initiated its s$eed of occurrence is limited only by amount of tissue thrombo$lastin released and :uantities of factor <" sometimes results from factors that activate in to motion the final

10

0;; and 0 in blood !ith severe tissue trauma clottin can occur in as little as 15 seconds. =n the other hand" intrinsic $ath!ay is much slo!er to $roceed" usually re:uires 1 to ' minutes to cause clottin . *+&," ) 2 : Conversion of prothrombin into thrombin : +rothrombin activator converts $rothrombin into thrombin is the $resence of calcium. Thrombin itself can accelerate this reaction by $ositive feed bac2 mechanism. 9i.e. activation of factor 0 !hich inturn accelerates formation of both e#trinsic and intrinsic $rothrombin activator). *+&," 3 : Conversion of fibrinogen into fibrin : Thrombin is a $rotealytic en*yme and converts soluble fibrino en into insoluble fibrin by removin ( lo! molecular !ei ht $e$tides from each molecule of fibrino en formin a molecule of fibrin monomer that has automatic ca$ability of $olymeri*in from lon fibrin threads. ;nitially the fibrin monomer molecules are held to ether by !ea2 noncovalent hydro en bondin and no cross lin2a e" therefore clot is !ea2 and easily bro2en. This is modified later into a dense ti ht a thrombin" covalent bonds and multi$le cross lin2a e ta2es $lace. Fibrinogen : ;t is a hi h molecular !ei ht $rotein 93"(0"000) Cone in blood 100 to %00 m @dl. 6ormed in liver re ate by fibrin stabili*in factor in the $resence of calcium ions and activation by !ith other monomer molecules to

11

Thrombin 6ibrino en Activated fibrino en +olymeri*ation

Hoss of ( $oly$e$tides Hoose strands of fibrin CaCC 6ibrin 9Ti ht clot)

6ibrin stabili*in factor

+rothrombin activatin factor

6actor < CaCC 6actor 0 Thrombin

+rothrombin Blood clot :

The fibrin threads run in all directions to form a mesh!or2 !hich entra$e RBCs" 5BCs and $latelets. The entire mass of fibrin mesh!or2 and the blood cells entra$$ed !ithin this is called blood clot. This clot adheres to the o$enin $revents blood loss. Clot retraction : of dama ed blood vessels and

12

A fe! minutes after clot is farmed" it be ins to contract and e#$ress a stra! colored fluid called serum !ithin 20 to '0 min. 4erum differs from $lasma as it lac2s fibrino en and other clottin factors and hence cant clot. +latelets are necessary for clot retraction and failure of clot retraction indicates that number of $latelets in circulatin blood is lo!. ,lectron micro ra$hs of $latelets in the blood clot sho! that they become attached to the fibrin threads to ether. 6urther more" $latelets entra$$ed in the clot continue to release $rocoa ulant substances" one of !hich is fibrin stabili*in factor" !hich causes more and more cross lin2in bonds bet!een the ad/acent fibrin threads. ;n addition the $latelets themselves contribute directly to clot contraction by activatin the $latelet thrombosthenin" actin and myosin molecules" !hich are contractile $roteins and cause stron contraction of the $latelet s$icules attached to fibrin. As the clot retracts" the ed es of the bro2en blood vessel are $ulled to ether" thus $ossibly or $robably contributin to the ultimate state of hemostasis. - ses of blood clot: The lyses of blood clot inside the blood vessel are called fibrinolysis. This occurs by a substance 2no!n as $lasma or fibrinolysin. The $roteins contain a en obulin called $lasmino en or $rofibrinolysin. 5hen a clot is formed" a lar e amount of $lasmino en is tra$$ed alon !ith other $lasma $roteins. The in/ured tissues and vascular endothelium release a $o!erful activator called tissue $lasmino en activator that a day or later after bleedin sto$s" convert $lasmino en to $lasmin. ;t di ests the fibrin threads and other substances in the surroundin blood" such as fibrino en" factors 0" 0;;; and <;; and $rothrombin. Therefore $lasmin causes lysis of clot and also destruction of many clottin factors" these by causin hy$ocoa ulability of blood.

13

.lasmins inhibitor : 4mall amount of $lasmin is formed in the blood all the time" !hich could seriously im$ede the activation of clottin system" blood also contains another factor 2 anti$lasmin" that bonds !ith $lasmin and inhibits it. Therefore the rate of $lasmin formation must raise above a certain clinical level before it becomes effective. The lysis of blood clot allo!s slo! clearin 9over several days) of e#traneous clotted blood in the tissue and allo!s reo$enin vessels. Hemorrhage/ -emorrha e in dental $ractice is commonly encountered after e#tractions" and durin endodontic thera$y is noticed in the follo!in situations. Acts as a si n of vital $ul$ 4i n of $erforation =ver instrumentation 1urin treatment of C sha$ed canals +erforatin internal resor$tion 6rom $erforations" durin access o$enin $re$arations ,ndodontic sur eries There are four methods by !hich the dentist can detect the $atient !ho may have a bleedin $roblem 1) a) b) c) d) Histor Bleedin $roblems in relatives Bleedin $roblems follo!in o$erations and tooth e#tractions Bleedin $roblems follo!in trauma 9cuts" etc) 8edications that may cause bleedin $roblems E As$irin E Anticoa ulants E Hon E term antibiotic thera$y. of clotted

1(

e)

+resence of illnesses that may have associated bleedin $roblems EHeu2emia E Hiver disease E -emo$hilia E Con enital heart disease

f) 2) a) b) c) d) e) f) ) 3) a) b) 35 sec c) d) e) 0)

4$ontaneous bleedin from nose" mouth" ears etc. .h sical e#amination Iaundice" $allor 4$ider an iomas ,chymoses +etechiae =ral ulcers -y$er$lastic in ival tissues -emarthrosis *creening laborator tests +TE $rothrombin time E normal 11 to 15 sec. A+TTE activated $artial throbo$lastin time normal is 25 to TT thrombin time normal is G to 13 sec BT bleedin time normal 1 to ' minutes +latelet count normal 1(0"000 to (00"000@m3 *urgical procedure e#cessive bleedin follo!in sur ery may be

first clue to underlyin bleedin $roblem.

C1&,2-&3+*
These are a ents !hich $romote coa ulation" and are indicated in hemorrha ic states.

15

6resh 5hole Blood or +lasma $rovide all the factors needed for coa ulation and are the best thera$y for the deficiency of any clottin factor7 also they act immediately. =ther dru s used to restore hemostasis are .E 1. 0itamin A A1 9from $lants) A2 9 $roduced by bacteria) A3 9 synthetic) 2. 8iscellaneous 6ibrino en Anti hemo$hilic factor Rutin Adrenochrome 8onosemicarba*one 1aily re:uirement of 0it A of adult 50 to 100 m @ day.

-1C&- H"M1*+&+!C* (*+4.+!C*)

1efE These are substances used to sto$ bleedin from a local a$$roachable site. They are $articularly effective on oo*in surfaces , . Tooth soc2et =$en !ounds They should never be in/ected , . 1. Thrombin . hemo$hilia" neurosur ery" s2in raftin E s$rayed on the bleedin surface. 2. 6ibrin . +re$ared from -uman $lasma and dried and used as sheets @ foam for coverin or $ac2in bleedin substances and ets absorbed in the body. 3. Delatin 6oam . it is s$on y elatin" available in various sha$es. ;t is moistened !ith saline and used for $ac2in !ounds" ets absorbed in 1 to 2 months. (. Russels vi$er venom . a$$lied locally" acts as thermo$lastin. 5. 0asocomtrictors lile 1& sol of Adrenaline may be soa2ed is sterile cotton ua e and $ac2ed" sto$s e$ita#is and other similar bleedin s.

1'

'. Astrin ents . li2e tannic acid is used for bleedin =ther substances !hich hasten clottin are. E E E factor

uns.

,#tracts of Hun s and Thymus E they have thrombo$lastin !hich causes ra$id coa ulation. 4odium or Calcium Al inate enhance clottin by activatin ha eman factor =#idi*ed cellulose causes clottin by activatin ha eman ;t is normal for blood to see$ from the site of a sur ical $rocedure for

several has after o$eration cloane the mouth !ith a mild rise 91@2 salt" J lass !ater -2=) tal2in # stron mouth rinses may stimulate bleedin should be controlled for fe! days. ;t bleedin continues a becomes $rofuse" try to locate the e#act s$ot the blood is comin from by ently flushin the mouth clean loo2in is a mirror. =nce you determine !here it is comin from" hold a $rice of au e" some to!elin or a tea ba a ainst the tissue and bone" a$$ly firm but entle $remise for 10 min !ith out movin the fin er a!ay from the site. 1o this is a sittin $osition. ;f heavy bleedin continues" call the sur eons office.

&3+!C1&,2-&3+*
5ef : These are substances !hich $revent or $ost$one coa ulation. They may act inside body 9is vivo) 7 outside body 9 in vitro) or used both in vivo and in vitro. 1/ E Heparin ;t is a naturally $roduced anticoa ulant" a con/u ated $olysaccharide" it is $roduced in mast cells and baso$hiles. 8ast cells are situated immediately outside the ca$illaries in lar e no of tissues or

1%

or ans !hich contain more connective tissue. These !anderin cells are abundant in liver and lun s. E Commercial he$arin is $re$ared is almost $ure form. ;t is e#tracted from liver and other or ans of animals. Mechanism of &ction ;t $revents clottin by its antithrombin activity. ;t also combines !ith antithrombin ;;; 9a $rotease inhibitor $resent in circulation) and a) b) <;" <;;. c) Clinical use ;ntravenous in/ection of he$arin 90.5 to 1 m .@ 2 body !t) causes bleedin time to increase from normal ' min to 30 or more minutes. The action of he$arin lasts a$$ 3 to ( hrs till it is destroyed by an en*yme in the blood 2no!n as he$arinase. ;n clinics hy$arin is used is .E 1) 2) 3) () To $revent intravascular blood clottin durin sur ery. 1urin dialysis !hen blood is $assed throu h artificial 2idney. 1urin cardiac sur ery" !hich involves $assin blood throu h heart lun machine After collectin blood from donor" if transfusion into the reci$ient is delayed" it is used as an anticoa ulant. 1urin treatment if too much is administered and serious bleedin crises occurs" then $rotamine acts s$ecifically as an antihe$arin"by inactivatin he$arin because it carries stron $ositive electrical char es" !hereas he$arin carries stron ne ative char es. Bse in laboratory ;t also activates antithrombin ;;;. Bses . as a anticoa ulant both in vivo and in vitro. Removes thrombin from circulation ;nactivates the active form of other clottin factors li2e ;<" <"

1F

As an anticoa ulant !hile collectin blood for various investi ations. 2/ Coumarin 5erivatives 1icoumoral and 5arfarin are the derivatives of coumarin. Mechanism of action ;t com$etes !ith 0it A for reactive sites is the en*ymatic $rocesses for formation of $rothrombin factors 0;;" ;<" < all of !hich form in the liver and re:uire 0it A. ;t bloc2s the action of 0it A. After effective dose is administered" the coa ulant activity decreases to a$$ro#imately 50 & of normal at end of 12 hrs and to 20& at end of 2( hrs. The $rocess is not bloc2ed immediately must a!ait consum$tion of $ro thrombin and other factors already $resent in $lasma. Kormal coa ulation returns 1 to 3 days after discontinuin thera$y. Bses they are used as oral anticoa ulants in clinical $ractice. 3/ E "5+& ,thylene 1iamine Tetra Acetic acid or sodium salt of ,1TA is a stron anticoa ulant. 8echanism of Action E 2ses E E 0/ E Administered intravenously in case of lead $oisonin Also used as anticoa ulant in lab 9in vitro). 1#alate Compounds ;t $revents coa ulation by formin calciumo#alate" !hich is $reci$itated later" thus they reduce blood calcium level. ;t is used as in vitro anticoa ulant. 6/ E Citrates 4odium" Ammonium or +otassium citrate can be used as anticoa ulants in lab 9invitro). Citrate combines !ith calcium is blood by removin calcium from blood

1G

to form calcium citrate and the reduction is calcium level $revents coa ulation. E 7/ Citrate is also used in blood blan2 as Acid Citrate 1e#trose 9AC1) or Citrate +hos$hate 1e#trose 9C+1) to store blood. Heparan -e$aran sul$hate has a !ea2 he$arin li2e activity and is $roduced mainly by vascular endothelium. The 2 macro lobulin is also a thrombin inhibitor. 8/ .rotein C Thrombin can bind !ith a com$ound called thrombomodulin 9$roduced by vascular endothelium) and causes chan es is thrombin" !hich no! acts on $rotein C to convert it into activated $rotein C !hich is an anticoa ulant. ;t acts on 0;;;a" so that factor 0;;; is inactivated. +rotein C is $roduced by the liver. 6or formation of activated $rotein C" a coEfactor $rotein 4 is re:uired. %ole of vit 9/ liver and vascular $all is hemostasis and coagulation/ .h sical methods to prevent clotting 1) 2) Cold . reducin tem$erature to about 50C $ost$ones clottin . Collectin blood in a container !ith smooth surface . li2e a silicon coated container $revents clottin .This is by inhibition of $latelet activation and formation of $ro thrombin activator. Vit 9 E -el$s in synthesis of a) +rocoa ulants" factor 0;;" ;<" ;<" < and $rothrombin b) Circulatory anticoa ulant" $rotein C. E vit A deficiency causes hemorrha ic disorders.

20

-iver :

;t is the site for synthesis of

a) +rocoa ulants li2e factors 0" 0;;" ;<" <" $rothrombin and fibrino en b) Anticoa ulants" he$arin" antithrombin ;;; and $rotein C. E Hiver failure thus can cause si ns and sym$toms of hy$ocoa ulabiity as !ell as hy$ercoa ulability. Vascular :alls a) tri b) 4ub endothelial layer is hi hly thrombo enic. Contact !ith blood ers off coa ulation. ,ndothelial layer is $rimarily o$$osin $rocoa ulants. c) 0asos$asm is an aid to hemostasis clottin as it is a barrier

bet!een blood and subendothelial layer. But also releases some

B-115 C1&,2-&+!13 +"*+*

E BT" CT" $latelet count" $rothrombrin time"thrombin time" activated $artial thrombo$lastin time. 1) Bleeding +ime : This is the time interval from oo*in of blood after a cut or in/ury till arrest of bleedin .Kormal duration is 1E ' mins. ;t is $rolon ed in $ur$ura and by the lac2 of $latelets. 2) Clotting +ime This is the time ta2en by the blood to clot after collectin from body. Kormal duration is ' to 10 min.;t is $rolon ed in hemo$hilia. 3) .rothrombin +ime ;t ives an indication of the total :uantity of $rothrombin in blood. The blood is collected and o#alated so that" the $rothrombin is not converted into thrombin" thus blood clottin is $revented. Then a lar e

21

:uantity of tissue thrombo$lastin !ith calcium is added to this blood. Calcium nullifies the effect of o#alate" and the tissue thrombo$lastin activates $rothrombin and blood clottin occurs. 1urin this $rocedure" the time ta2en by blood to clot after addin tissue thrombo$lastin is called prothrombin time. Kormal duration is about 12 sec. ;t is $rolon ed in deficiency of $rothrombin and other factors ;" 0" 0;; and <. -o!ever" it is normal in -emo$hilia/ The test to measure the $rothrombin time is E ;uic<ies one stage method

B-""5!3, 5!*1%5"%*
1) Bleeding caused b Vit 9 deficienc : E ,#ce$t for fe! most of the clottin factors are $roduced in liver. Therefore liver diseases he$atitis" cirrohosis and acute yello! atro$hy de$ress clottin system E 0it A is needed for formation of $rothrombin"factor 0;;" factor ;<" factor < and $roteinC in liver. Therefore 0it A deficiency causes insufficiency of these factors bleedin . E 0it A is synthesi*ed in D;T by bacteria. ;n D;T disease" deficiency occurs as a result of $oor absor$tion of fats from D;T because 0it A is fat soluble and ordinarily absorbed into blood alon !ith fats. E =ther cause failure of liver to secrete bile into D;T 9due to obstruction of bile duct or liver disease) become lac2 of bile $revents ade:uate fat di estion and absor$tion" therefore $oor 0it A absor$tion. E =rdinarily" if 0it A is iven to deficient $atient ( to F hrs before o$eration and liver $arenchymal cells are at least one half

22

normal in function" sufficient clottin factors !ill be $roduced to $revent e#cessive bleedin . 2) Hemophilia ;t is a se# lin2ed inherited disease" transmitted as a recessive trait. Causes . ;t is caused by deficiency of 6actor 0;;; and ;<. 6actor 0;;; classical hemo$hilia or hemo$hilia A. 6actor ;< Christmas disease or hemo$hilia B. F5& of $eo$le !ith hemo$hilia are affected by -emo$hilia A and remainin 15& by -emo$hilia B. ;t occurs due to lac2 of formation of $rothrombin activator" hence coa ulation time is $rolon ed. Bleedin time and $rothrombin time are normal. Both the factors are transmitted enetically by !ay of female chromosome" therefore they !ill never have hemo$hilia because at least one of her t!o L< chromosomes !ill have a$$ro$riate enes. -o!ever if one of her < chromosome is deficient" she !ill be a hemo$hilia carrier" transmittin the disease to half of her male offs$rin s and transmittin the carrier states to half her female offs$rin s. Bleedin !ill not occur e#ce$t after trauma" but the de ree of trauma re:uired to cause severe and $rolon ed bleedin may be so mild that it is hardly noticeable. Bleedin lasts for literally !ee2s after e#traction of a tooth. 6actor 0;;; is com$osed of 2 se$arate com$onents" a very lar e com$onent !ith mol.!t in millions and another smaller com$onent !ith molecular !ei ht of about 2"30"000 .This small com$onent is most im$ortant in intrinsic $ath!ay of clottin " and its deficiency of this $art of factor 0;;; that causes classical hemo$hilia. -emo$hilia C caused by deficiency of +lasma thrombo$lastin antecedent 9+TA factor <;)

23

E Kot se# lin2ed" transmitted to both male and female decedents by male and $robably females. =ral si ns and sym$toms bleedin from sli ht cause 9tooth brush) lar e clots develo$ around teeth. E 4heddin and eru$tion of teeth may be associated !ith oo*in of blood for days or !ee2s. Tooth e#traction ;st indication of disease +reatment : ;n/ection of $urified factor 0;;;. 9unfortunately cost of factor 0;;; is very hi h and availability is limited because it is athered only from human blood and in e#tremely small :uantities.

5"3+&- M&3&,"M"3+
Heamophilia & Conservative dentistry ;f conservative treatment is not tolerated !ithout anaesthesia"$a$illary or intrali amentary infiltration may achieve sufficient anal esia. Care must be ta2en not to let the matri# band in/ure the $eriodontal tissues 9to be safe rubberdam is used) Endodontics To$ical a$$lication of 10& cocaine to e#$osed $ul$ is choice for vital $ul$ e#tir$ation. TreatmentE re$lacement of missin factors either by $lasma @$lama fractions is $rimary form of thera$y.6actor 0;;; is found in only fresh $lasma"but factor ;< remains stable and active for lon $eriods in stored $lasma.6actor 0;; can also be re$laced by cry$reci$itate9cryofactor 0;;;).,$silonEamino ca$roic acid 9Amicar) a dru that bloc2s action of fibrinolysin has also been found to be hel$ful ad iven $rior to and follo!in dental e#tractions.6actor ;< deficiency can be treated by fresh or stored $lasma as !ell as by the use

2(

of $rothrombin com$le# concentrates that contain factors 0;;";<"<.6actor ;< is re$laced !ith fresh $lasma. 3) Von :illebrand 5isease Characteri*ed clinically by s$ontaneous bleedin from mucous membrane7 from !ounds7 and $rolon ed bleedin time in $resence of normal $latelet count Transmitted as an autosomal dominant disorder. Ty$e ; . reduced :uantity of circulatin 056. 0on 5illebrand factor is a $rotein secreted by endothelial cells and $latelets. This $roteins is res$onsible for adherence of $latelets to endothelium of blood vessels durin hemostasis after an in/ury. Ty$e ;; E 1eficiency of the lar er com$onent of factor 0;;; 0on 5illibrand disease. 0) .urpura -ere bleedin time is $rolon ed" ho!ever clottin time is normal. +ersons have a tendency to bleedin from many small venules or ca$illaries resultin is small $unctuate hemorrha ic s$ots throu h all the body tissues" the s2in dis$lays many small $ur$lish 9+ur$uric) blotches @ s$ots" hence the name $ur$ura. They de$endin on cause . +hromboc topenic purpura ) $latelets are very im$ortant for re$air of minute brea2s is ca$illaries and other small vessels. ;n bone marro! disease" the $latelet $roduction is affected causin deficiency state" the number fallin belo! a value of a$$ 50"000 @ lt 9normal 150"000 to 300"000). The deficiency of $latelets 9thrombocyto$enia) leads to $ur$ura" !hich is called Thrombocyto$enic $ur$ura. Hevels as lo! as 10"000 @ ml are fre:uently lethal. b) +hromboesthenic purpura $ur$ra occurrin due to abnormal $latelets is circulation" althou h the number be normal.

25

c) !diopathic thromboc topenic purpura ;t is the $ur$ura occurrin due to un2no!n causes. The $latelet count is reduced due to develo$ment of s$ecific antibodies !hich may occur after transfusion of blood from another $erson" but usually they result from develo$ment of autoimmunity to the $ersons o!n $latelets the cause is un2no!n. +reatment : Relief from bleedin for 1 to ( days can often be effected is the $atient by ivin fresh !hole blood transfusions. Also" 4$leenectomy is very hel$ful" sometimes effectin almost a com$lete cure"because s$leen removes lar e number of $latelets" $articularly dama ed ones from blood. +hrombosis : 1ef. coa ulation of blood inside the blood vessel is called throbisis or ;ntravascular blood clottin . Complications : Thrombus durin thrombosis" there is occlusion of lumen of blood vessels by solid mass of $latelets" red cells @or clot" !hich is called Thrombus. The thrombsis due to a lutination of RBC is called A lutinative thrombsis. "mbolism and "mbolus ,mbolism is the $rocess in !hich the thrombus or $art of it is detached and carried in blood stream to arrest the blood flo! in any $art or re ion of the body. ,mbolus it is the thrombus or $art of it" !hich causes embolism. e . obstruction of blood flo! in lun s $ulmonary embolism Brain cerebral embolism -eart coronary embolism !nfarction and !nfarct

2'

;nfarction is the sto$$a e of blood su$$ly to any or an or $art of the or an due to embolism. ;nfarct it is the affected area. e . 8yocardial infarction. Causes : a. ;n/ury to blood vessels durin infection or mechanical obstruction the endothelial linin thrombosis. b. Rou hened endothelial linin infection" dama e or arteriosclerosis" the endothelium becomes rou h and initiates clottin . c. 4lu a ishness of blood flo! decreased rate of blood flo! causes re ation of $latelets and formation of thrombosis slo!ness of of bet!een is dama ed and this initiates

blood flo!. occurs in reduced cardiac action" hy$otension and lo! metabolic rate" $rolon ed conferment to led and immobility of lin2s. d. A lutination of RBC it can occur by forei n anti ens or to#ic substances. The clottin a lutination of RBC. occurs inside the blood vessel durin

e. To#ic Thrombosis E it is common due to action of chemical $oisons li2e arsenic com$ounds" mercury" $oisonous mushrooms and sna2e venom. f. Con enital absence of +rotein C +rotein C is a circulatin anticoa ulant" !hich inactivates factors 0 and 0;;;" Thrombosis occurs is the absence of this $rotein. Con enital absence causes thrombosis and death in infancy. 5isseminated intravascular coagulation This occurs due to initiation @ activation of clottin mechanism is !ides$read areas of circulation" resultin thrombo$lastins into the blood. from the $resence of lar e amounts of traumati*ed or dyin tissue in the body that releases tissue

2%

The clots are small but numerous and $lu a lar e share of small $eri$heral blood vessels. This occurs es$ecially is se$tisemic shoc2 in !hich either circulatin bacteria or bacterial to#ins es$ecially endoto#ins activate the clottin mechanisms. The $lu in of small $eri$heral vessels reatly diminishes delivery of o#y en and other nutrients to the tissues a situation that e#acerbates shoc2 $icture. A $articular effect of 1;C that the $atient fre:uently be ins to bleed. The reason for this is that so many of the clottin factors are removed by the !ides$read clottin that too fe! $rocoa ulants remains to allo! normal emostaris of the remainin blood. Clinical considerations 1urin day to day clinical $ractice it is very im$ortant for the dentist to ta2e u$ all the $recautionary measures as !ell as to follo! /udiciously the $rinci$les and ste$s of various treatment modalities to $revent any under hemorrha e to occur. 1) !mmediate %oot fillings : 4ome o$erators" $rovided the $ul$ is vital and !ith out evidence of ross infection" insert a root fillin immediately after $re$aration of canal. This has 2 dra!bac2s or anisms may remain after $re$aration and may survive" later causin $eria$ical disease. 6ollo!in trauma of $ul$ectomy" haemorrha e may occur !hen the vasoconstrictor action of anesthetic solution ceases "the root fillin $revents blood enterin the root canal" hemorrha e into $eria$ical re ion ta2es $lace leadin to a$ical $eriodontitis discomfort si nificantly more $ost o$erative $ain. 2) .revention of 5iscoloration 1iscoloration of tooth subse:uent to RCT can in most instances be $revented by ivin $ro$er attention to various as$ects of treatment.

2F

;t is im$ortant that the o$enin into the $ul$ chamber is lar e enou h to $ermit the removal of all $u$al debris in cro!n.After removal of vital $ul$ all traces of blood should be eliminated from the $ul$ chamber. -aemorrha e should have ceased by the time the $ul$ cavity is dressed and sealed. Har e strands of tissue coronal to level at !hich $ul$ !as severed should not be allo!ed to remain" since they are li2ely to bleed later and the above said may enter the dentinal tubules and discolour the tooth.

3)

5uring *urgical +reatment Dood anesthesia is essential durin sur ical endodontics.+rofound

lon lastin anesthesia can be achieved usin 2& li nocaine 9lidocaine) !ith 1.F0.000 adrenaline 9e$ine$hrine). The vasoconstrictor in such a anesthetic $rolon s the duration of anesthesia heamostasis to $rovide a blood free o$erative site. ;f bleedin from ed e of incision and from cancellous bone is $resent" then $ac2in the bone cavity !ith a len th of ribbon au*e" 1 cm !ide soa2ed is 1@1000 adrenaline should be ti htly $ac2ed into the cavity" the fla$ re$laced" and left for a minute or so. 6ollo!in its removal" locali*ed bleedin is ceased. After sur ery fla$ is returned to ori inal $osition and stabili*ed !ith sutures" firm $ressure is then a$$lied to tissue fla$ !ith au*e soa2ed is saline for several minutes. This minimi*es si*e of blood clot bet!een tissue and cortical bone" so that there !ill be less $ost o$erative s!ellin and discomfort and $ro$er fast healin . 4ome $ost o$erative instructions to $atient to $revent bleedin 1. Avoid strenuous activity until ne#t day" since this tends to ma2e !ound bleed. 2. 1ont smo2e @ drin2 alcohol and hel$s to induces

2G

3. 1ont retract li$ or chee2 to ins$ect re ion as it !ill $ull on tissue fla$. (. Brush normally on other :uadrants" avoid sur ical site till sutures are removed. Measurement of acute blood loss := Assessment and mana ement of blood loss must be related to the $re e#istin circulatin blood volume" !hich can be derived from $atients !ei ht . infant F0 to F5 ml @ 2 adult 55 to %5 ml @ 2 8easurin blood loss E Blood clot if the si*e of clenched fist is rou hly e:ual to 500 ml. E E 4!ellin in closed M 9tibia) 500 to 1500 ml 4!ab !ei hin in the o$eratin theater" blood loss can be measured by !ei hin s!abs after use and subtractin the dry !t. The resultin total obtained 91 N 1 ml) is added to the role of blood collected in suction @ draina e bottles. Treatment E E dressin E E Restore blood volume immediately. +ressure and $ac2in first aid treatment is a $ressure !hich should be bound on ti htly. +ac2in rolls of !ide au*e. +osition and rest elevation of limbs e reca$tured varicose veins" em$loys ravity to reduce bleedin and causes vasoconstriction.

, di ital $ressure 9fore fin er and thumb)" cloth ra 9e$ista#is)

B-115 +%&3*F2*!13
;ndications 1. 8a/or road traffic accident

30

2. chronic blood loss 3. $ost o$erative in $atient !ith mali nancies bleedin disorders (. intra o$erative ma/or sur ery &dvantages : E 0olume re$lacement E ;ncrease =2 carryin ca$acity E Re$lacement of clottin factors

Complication +yre#ia E +latelet saniti*ation E E E+lasma aller y ERenal failures

C13C-2*!13
6or normal e#istence of man the coa ulation of blood is of at most im$ortance as !ithout this function man !ould be to death. -ence it is very im$ortant to record a $ro$er history and ta2e all the caution !hile treatin before its too late" as it is said its better to prevent than to cure.