The Physiology Of Blood

HEMOSTASIS

By Dr. M. Anthon y Davi d.MD . NOMAD:2005:BP:Hemostasis

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HEMOSTASIS: INTRODUCTION   

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Hemo : Bl oo d Stasi s : Ke ep i n th e same state . Hemo stasi s r efers to th e var io us mechan isms exist in g to k ee p b lood i n t he liqui d state an d w ith in th e intr av asc ular com par tm ent. Th ey includ e:   

The int act e nd othe lium. In viv o antico ag ulants . Proco ag ulant mechani sm s. NOMAD:2005:BP:Hemostasis

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HEMOSTASIS: SEQUENCE OF EVENTS   

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VASC UL AR SPA SM . PLAT ELET PLUG FO RMAT ION. BL OOD CLOT FORMA TI ON: COA GUL AT ION. CL OT RE TRA CTIO N . FIBRI NOL YS IS . REO RGA NISAT IO N. REP AI R & RE GE NERA TION. NOMAD:2005:BP:Hemostasis

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VASCULAR SPASM

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VASCULAR SPASM    

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Als o c all ed Va soc onst ricti on. Is spontaneou s . Imme diate bu t tempo rary. Last s f or a m ax imu m o f 30 mi nutes . Ca us e: 

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My oge nic: from th e sm ooth musc les Neur oge nic: fro m th e ner ves NOMAD:2005:BP:Hemostasis

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VASCULAR SPASM

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PLATELET PLUG FORMATION 

Ca us ed by e xpos ure o f bl oo d to:  

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Br oke n e ndoth elium Underl ying col lage n.

St eps in P P Forma tion: P la tel et …     

Acti vatio n Adh es io n Agg regatio n Cohesi on Temp orary & perm anent p lug NOMAD:2005:BP:Hemostasis

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COAGULATION OF BLOOD

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COAGULATION: BASIC THREE STEPS 

FORMATION OF PROTHROMBIN ACTIVATOR.

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FORMATION OF THROMBIN.

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CONVERSION OF FIBRINOGEN TO FIBRIN. NOMAD:2005:BP:Hemostasis

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PROTHROMBIN ACTIVATOR FORMATION 

Begins in response to:  

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Rupture of a vessel. Damage to blood.

A series of reactions result in the formation of a chemical complex. This complex activates Prothrombin. This can be formed either by an extrinsic or intrinsic pathway. NOMAD:2005:BP:Hemostasis

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CONVERSION OF PROTHROMBIN TO THROMBIN 

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Prothrombi n Ac ti va tor is th e cata lyst . Usu ally it is the Ac ti va te d F act or X , along wi th t he Fa cto r V & Phosphol ipi ds, whic h f orms the Act ivator. It he lps c onve rt P rothrombi n. Res ul ts i n t he f orma tion o f Thrombi n . NOMAD:2005:BP:Hemostasis NOMAD:2005:BP:Hemostasis

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FIBRIN FORMATION  

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Thrombi n a cts now as the c at al ys t. It c onve rts t he pl as ma pr ote in Fibri nogen i nto Fibrin . Fibri n m onome r is c onverte d to a pol yme r by Fa cto r XI II or FS F . Thes e f ibr in threa ds fo rm a mes hwo rk . Bl ood c el ls g et e nta ngled in i t to form the ClotNOMAD:2005:BP:Hemostasis or Coa gulu m .

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C O A G U L A T I O N: B A S I C S T E P S

PRO THROMBIN

TH ROMBI N FI BRI NOG EN

FI BRI N MON OMER

FIBRI N POL YMER( THREADS) CO AGUL UM FORMED

CEL LS EN TAN GLED

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HEMOSTATIC HOMEOSTASIS P R O C O A G U L A N T S

A N T I C O A G U L A N T S NOMAD:2005:BP:Hemostasis

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COAGULATION FACTORS: PROCOAGULANTS

I

FIBRIN OGEN

II

PRO THROMBI N MW: 69,0 00

III

TI SS UE TH ROMBOPL AS TIN

IV

FRE E CA LCI UM I ON S

V

VI

MW:3,50,00 0

Ca ++

PROACCE LERI N, LABI LE FACTOR,ACC EL ERATOR GL OBUL IN AB SEN T I N SE RUM NO S UC H F ACTOR NOMAD:2005:BP:Hemostasis

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COAGULATION FACTORS: PROCOAGULANTS

VI I VI II

SE RUM PROTH RO MBI N CON VERS ION ACCEL ERATOR (SPCA AN TI H EMOPH IL IC) FACTOR A

IX

CH RI STMAS F ACTOR

X

STUART -P ROWER FA CT OR

XI

PLA SMA THROMBOPL AS TIN AN TECEDEN T (PT A) HAGEMAN F ACTOR , GL AS S CON TACT FACT OR FI BRI N STAB ILIZIN G F ACTOR

XII XII I

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EXTRINSIC PATHWAY: A FLOW CHART TISSU E TRA UMA

VII :SPC A

TISSUE THRO MBO PLAS TIN (I II) GL YCO PRO TEIN + PHOSP HOLI PID

FACTOR X

X a

FACTOR IV : Ca++

FACTOR V

PROTHROMBIN AC TIVATOR PROTHROMBIN

THRO MBI N

FACTOR IV: Ca++

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+v e F E E D B A C K

ONT O THE OTHER TWO ST EP S OF 18 COAGU LAT ION

INTRINSIC PATHWAY: A FLOW CHART TRAUM A TO BLO OD; EXPO SU RE TO COLL AG EN XII XII a HMW KININO GE N PRE KALL IK RE IN XI XIa IX

IXa

VII I Ca ++ THRO MB IN X

Xa

PL AT ELE T PHOSP HOLIP ID S

Ca ++ V

PROTHRO MBIN AC TIVATOR PROTHROMBIN

THRO MB IN NOMAD:2005:BP:Hemostasis

Ca

++

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DIFFERENCES BETWEEN EXTRINSIC & INTRINSIC PATHWAYS 

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EXT RINSIC The e ss enti al, tr iggering s tep is Tiss ue tra um a . Is exp lo sive in na ture. Can be c omp lete d in 15 se cond s . No inhi bito ry mechani sms to count er this p at hway.

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INTRINSIC The trigger is the exposure of Collagen in the vascular wall to Factor XII & Thrombocytes. Is slow to proceed. Can take 2 to 6 minutes. Many inhibitory or antagonistic mechanisms exist in the blood.

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IN VIVO ANTICOAGULANTS 

IN VI VO:       

Smoo th an d i ntact e ndoth elium. Hepar in . Th rom bin Pro stacycli n Th rom bax an e A2 An tiTh rom bin II I Th rom bomo dul in Plasm inoge n Sy ste m( Fi brinoly si ns) NOMAD:2005:BP:Hemostasis

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IN VITRO ANTICOAGULANTS  

HEPARI N. VI TAM IN K AN TAGON ISTS(MOA:  VI I, I X &X)   

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Dic oumarol Warfarin Dip he nad io ne.

CA LC IU M C HEL ATORS    

Po tass ium-A mm onium O xalat e. Sod ium/P otass ium Oxalate Sod ium C itrate 3.8% s ol utio n. Ethylene D iamine T etra A cet ic A cid . ( EDTA) NOMAD:2005:BP:Hemostasis

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HEMOSTASIS: APPLIED ASPECTS 

ST AT ES OF D ECREASE D C LOTTI NG: 

VI TAMIN K DEF ICI ENCY.

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HEMOPH ILIAS

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TH ROMB OCYT OP EN IA: I TP TH ROMB ESTH EN IA AF IBRINO GEN EMI A: Abse nce o f Fibrinoge n i n th e Plasm a.Co agul ati on not poss ib le . Ve ry rar e.

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HEMOSTASIS: APPLIED ASPECTS 

ST AT ES OF E XCESSI VE COA GUL AT ION:  

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At her osc lero si s, Thromb osi s. Di sse mi nate d In travasc ul ar Clo tti ng (DIC ) Th rom boem bolism

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HEMOPHILIAS   

Bl eedi ng D isorde rs. Se en e xc lu sive ly i n M ales . Ca us es : 

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Fac to r VII I d eficiency: “ Cl assi cal Hemo philia” 85% cases. Fac to r IX deficiency: “C hr istm as Di se ase” 15 %.

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HEMOPHILIAS 

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Gen eti call y t ran sm itte d by a gen e on th e recessi ve X chromo so me . Femal es can b e ca rriers, m aki ng t heir so ns dise ase d! Sym ptom s: 

Unst op pab le b le ed ing :  

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Fr om wo unds. Into jo ints, e tc.

Invest igati on: P rol onged Cl otti ng Time. Tr eatme nt: Now , Ge neti cal ly engin eered Pure Factor VI II or IX as need ed. NOMAD:2005:BP:Hemostasis

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THROMBOCYTOPENIA: ITP 

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Norma l T hro mboc yte Cou nt: 1. 5 – 4. 0 Lakh s/C u.mm. Crit ic al T hrom bocyte Count: <5 0, 000/Cu .m m. Sympt oms :  

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Bl eeding te ndency incr eases. Small pun cta te h emo rrhage s un der t he sk in. Called Pur pur a .

So it i s c alle d Throm bocytope nic NOMAD:2005:BP:Hemostasis pu rpura

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P U R P U R A NOMAD:2005:BP:Hemostasis

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THROMBOTIC DISORDERS 

ATH EROSCL EROSI S: TH ROMBOS IS:   

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Cor on ary Cer ebral Pulm on ary

DISSE MINA TED I NTRAV ASCU LAR CL OT TING: D IC: C ONSUMP TION COA GUL OP AT HY :   

To xi ns from Bacte ri a Pro stati c Can ce r Acute My elo id Leuk emi a

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THROMBOTIC DISORDERS 

TH ROM BOE MBOL IS M:      

Thr omb i ar e fo rme d. Bits of it m ay b e d etac hed. They are called emb oli . Embol i mo ve up in the circulating They o bst ruct so me ve ss els . Can cause ‘em bol ism’:   

b lo od .

Cor ona ry Ce rebr al Pulm ona ry NOMAD:2005:BP:Hemostasis

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