Coagu|opath|es and 8|eed|ng D|sorders

karl 1homas, Mu
D|sc|osure and Contact Informanon
karl 1homas, Mu
ulvlslon of ulmonary and Crlucal Care Medlclne
ueparLmenL of lnLernal Medlclne
unlverslLy of lowa Carver College of Medlclne
karl-Lhomas[ulowa.edu

ulsclosures:
up1ouaLe
Cb[ecnves
laLeleL ulsorders and laLeleL 1ransfuslon
Lxplaln causes and lmpllcauons of LhrombocyLopenla
uescrlbe lndlcauons for plaLeleL Lransfuslon
8ecognlze cllnlcal syndromes of Pl1, l1, 11, PuS
Coagulauon lacLor ulsorders and ComponenL use
uescrlbe lndlcauons for ll and cryopreclplLaLe use
8ecognlze and manage ulC and Masslve 1ransfuslon
Manage bleedlng compllcauons assoclaLed wlLh
warfarln and novel oral coagulauon lnhlblLors
Lxplaln problems assoclaLed wlLh use of lvlla
1hrombocytopen|a
Convenuonal denluon < 130,000/mm3
Change ln plaLeleL counL ls lmporLanL even lf absoluLe
number ln normal range
up Lo 43 of all general lCu pauenLs
CounLs fall wlLh acuLe lllness and reach nadlr by
day 3-4
auenLs who have LhrombocyLopenla whlch perslsLs
longer have lncreased morLallLy
Akca, CrlL Care Med, 2002, 30:733
SLrauss, CrlL Care Med, 2002, 30:1763
1hrombocytopen|a: Imp||canon of Dynam|c kesponse
nl[sLen, CrlL Care Med,
2000, 28:3843
Survlvors
nonsurvlvors
1hrombocytopen|a: Cutcome Assoc|anons
1hrombocyLopenla assoclaLed wlLh lncreased lCu
LCS, hosplLal LCS, morLallLy
vanderschueren,
CrlL Care Med, 2000
28:1871
WhlLe bars: dlsLrlbuuon
of plL counL
Crey bars: morLallLy by
plL counL
DDx: 1hrombocytopen|a
lnfecuon, sepsls and chronlc llver dlsease accounL for
abouL 1/2 of all lCu pauenLs wlLh LhrombocyLopenla
uecreased producuon
lnfecuons (L8v, Plv, parvovlrus, mumps, varlcella, rubella, Pep C,
rlckeusla)
urugs/Loxlns (chemoLherapy, alcohol)
nuLrluonal declency (812, folaLe)
Myelodysplasuc / myeloprollferauve dlsease
lncreased desLrucuon
lmmune vs. non-lmmune
lnfecuon, sepsls, ulC, 11, l1, Pl1, drug-lnduced, posL-Lransfuslon
purpura
ulluuonal, rapld exLravascular loss or sequesLrauon
Masslve hemorrhage + Lransfuslon, hypersplenlsm
Ind|canons for |ate|et 1ransfus|on
Acuvely 8leedlng auenLs - lmprove conLrol of
bleedlng ln pauenLs wlLh LhrombocyLopenla or
dysfuncuonal plaLeleLs
lnLracranlal or lmmedlaLely llfe-LhreaLenlng bleedlng:
Lhreshold for Lransfuslon -100,000/mm3
MosL bleedlng slLuauons - 30,000/mm3
laLeleL funcuonal defecLs - any or normal plaLeleL counL
CongenlLal - Clanzman, 8ernard-Souller
Acqulred (medlcauon relaLed)
ASA, nSAlu, dlpyrldamole, clopldogrel, uclopdlne
abclxlmab, epumaude, uroban
|ate|et 1ransfus|on 1hresho|d for
|anned rocedures or Surg
neurosurg, ma[or vascular : -100,000/mm3
Ceneral surglcal: -30,000-100,000/mm3
Lndoscopy: -30,000/mm3 wlLh blopsles and Lherapeuuc
lnLervenuons, - 20,000/mm3 for dlagnosuc procedures
CvC, Lumbar puncLure, Lhora/paracenLesls, bone
marrow blopsy: 20,000/mm3
Zeldler, 1ransfuslon, 2011, 31:2269
vavrlcka, Ann PemaLol 2003, 82:370
rophy|acnc |ate|et 1ransfus|on
8educe rlsk for sponLaneous bleedlng
8one marrow suppresslon: <10,000
Leukemlas: <10,000
AcuLe promyelocyuc leukemla: <30-30,000
Cllnlcal ad[usLmenL: lncrease Lhreshold for
lever and lnfecuon
Comblned coagulopaLhy
uebaLed - dose, prophylaxls v. Lherapeuuc
Schler, ! Clln Cncol, 2001, 19:1319
LsLcourL, Cochrane uaLabase Sys 8ev, 2012
rophy|acnc |ate|et 1ransfus|on
SLanworLh eL.
al. nL!M,
2013,
368:1771
600 pauenLs
wlLh
hemaLologlc
mallgnancy
8C1 Lo
prophy. aL
10k or only
wlLh bleedlng
?ou are consulung on a 68 y.o. posLoperauve CA8C pauenL
on posL-op day 6 ln SlCu wlLh perslsLenL CPl LreaLed wlLh
dlureucs, ACL-l and unfracuonaLed heparln. She ls
bedbound. She has unllaLeral leg edema wlLh doppler
ulLrasound showlng uv1. ln8 ls 1.3, a11 31 seconds.
PemaLocrlL decreased from 37 Lo 32 slnce admlsslon.
Change ln plaLeleL counL from 290,000 Lo 117,000. 8un/Cr
36 / 3.3.
?ou sLop Lhe sc. heparln. WhaL ls Lhe slngle besL nexL sLep?
A) lnserL lvC lLer
8) lnluaLe conunuous unfracuonaLed heparln lnfuslon
C) lnluaLe subcuLaneous low molecular welghL heparln
LreaLmenL
u) 8egln conunuous argaLroban lnfuslon
L) erform caLheLer LrombecLomy
nepar|n Induced 1hrombocytopen|a
41s: 1hrombocyLopenla, 1lmlng, 1hrombosls,
al1ernauve dlagnoses excluded - good negauve
predlcLor
2. reLesL
probablllLy
1. Cllnlcal
ManlfesLauons
presenL?
3. LaboraLory
Lesung
Pl1 Cllnlcal
ulagnosls
+
Cuker, 8lood, 2012, 120:4160
retest robab|||ty of nI1
Ma[or 8lsk facLors (C8 >3)
Peparln durauon >4 days
8ecenL heparln (pasL 100 days)
use of unfracuonaLed heparln
8lsk > 1
osL op pauenL wlLh ulP (prophylacuc or Lherapeuuc) > 4 days
8lsk 0.1 - 1.0
Medlcal / obsLeLrlc pauenLs ulP >4 days
osL-op pauenL wlLh LMWP > 4 days
8lsk < 0.1
Medlcal / obsLeLrlc pauenLs LMWP > 4 days
Any pauenL recelvlng ulP or LMWP < 4days
Warkenun 2008, ChesL, 133:340S - 380S
nI1 C||n|ca| I|nd|ngs
laLeleL counL fall > 30 from basellne
Speclc Lemporal pauern (3-14 days aer heparln
exposure)
AbsoluLe plaLeleL counL < 130,000 / mm3 - less speclc
ApproxlmaLely 1/4 of pauenLs Lhrombosls precedes
LhrombocyLopenla
varlauons
8apld onseL Pl1 - 1 -3 days followlng heparln - ln pauenLs recenLly
exposed Lo heparln
uelayed onseL Pl1 - 3 - 3 of pauenLs - beglns several days aer
heparln sLopped
Warkenun 2008, ChesL, 133:340S - 380S
Laboratory tests for nI1
LvaluaLe for oLher causes of LhrombocyLopenla
(coags, perlpheral smear)
AnuplaLeleL Anubody assays - sensluve buL noL
speclc
ueLecLs lgC, lgM, lgA
Cood sensluvlLy, buL lower speclclLy
luncuonal plaLeleL assays - besL speclclLy
Assay for acuvauon of plaLeleL by lmmunoglobulln
blndlng Lo plaLeleL lc recepLor
SeroLonln release assay
Plgher speclclLy Lhan anubody assay
1reatment of nI1
lmmedlaLely dlsconunue all heparln
Anucoagulauon
WP?: A1 8lSk lC8 1P8CM8CSlS
lv 1hrombln lnhlblLors - argaLroban, leplrudln,
blvallrudln conunuous lnfuslon uLraLed Lo a11
1.3-2.3x basellne
Long-Lerm anucoagulauon wlLh warfarln
Warfarln should noL be used alone as lnlual 1x
Warfarln should noL be lnluaLed unul plaLeleL counL
subsLanually recovered, mlnlmum overlap 3 days
non-heparln lv anucoagulanL should be conunued
unul warfarln dose sLable
A 22 yo woman presenLs wlLh headache, faugue x 3 days.
She has focal neuro sympLoms buL ls somnolenL. normal
pulse and 8, 1 38.0. She does noL have nuchal rlgldlLy or
phoLophobla. Skln has peLechlae on mucosal membranes
and legs. 8un/Cr 61/3.3, LuP 842, W8C 10.7, Pgb - 8.9
g/dL, laLeleL 19,000/mm3. ln8 1.1, a11 24 seconds.
Lumbar puncLure wlLh 2 lymphocyLes/ hpf. 1here are
schlsLocyLes on perlpheral smear.
WhaL LreaLmenL would you pursue rsL?
A) lasma exchange
8) lasma lnfuslon
C) laLeleL Lransfuslon
u) Cerlaxone and vancomycln
L) Plgh dose corucosLerolds and lv lmmnoglobulln
Immune 1hrombocytopen|c urpura
lsolaLed LhrombocyLopenla
no abnormallues ln coagulauon umes
no abnormallues ln W8C or 88C
8esulLs from anubodles Lo plaLeleL glycoproLelns
ldlopaLhlc (prlmary)
Secondary - collagen vascular dlsease, medlcauons
1reaLmenL
remove oendlng agenL lf known
CorucosLerolds
lv lg
1hrombonc 1hrombocytopen|c urpura
(11)
1exLbook feaLures:
1hrombocyLopenla wlLh or
wlLhouL purpura
Anemla (mlcroanglopaLhlc
hemolysls)
8enal fallure / lnsumclency
neurologlc ndlngs:
headache, alLered menLal
sLaLus, selzures
lever
MorLallLy 10-33
ueclency of AuAM1S-13
hup://w3.ouhsc.edu/plaLeleLs/laLeleL
20lcs/laLeleLs2.[pg
Laboratory Ieatures and 1reatment of 11
Severe LhrombocyLopenla (<30,000 k / mm3)
Pemolyuc anemla wlLh schlsLocyLes
Consumpuon of coagulauon proLelns nC1 a feaLure
Coagulauon abnormallues mlld
ulerenual dlagnosls:
PuSAuLolmmune hemolyuc anemla, malarla, PLLL syndrome,
anuphosphollpld Ab, ulC, valvular hearL dlsease, dlssemlnaLed carclnoma,
Lvans syndrome - congenlLal AlPA + l1
1reaLmenL
lasma exchange. Conslder sLerolds + rlLuxlmab ln relapse
slLuauon or fallure Lo respond Lo ex.
11 - |asma exchange
CuLcome of severe adulL Lhrombouc mlcroanglopaLhles ln Lhe lCu,
ene eL.al., 2003, lnLenslve Care Med, 31:71-78
nemo|ync Urem|c Syndrome
MlcroanglopaLhlc hemolyuc anemla - overlaps wlLh 11.
1erm 11-PuS oen used Lo descrlbe dlsease ln adulLs
PuS used mosL commonly Lo descrlbe chlldren wlLh
LhrombocyLopenla, bloody-dlarrhea syndrome and renal dlsease.
1rlggered by Loxln-medlaLed endoLhellal damage and dluse
acuvauon of complemenL sysLem
AssoclaLed wlLh enLerohemorrhaglc e.coll whlch produces veroLoxln
(shlga-llke Loxln).
C137:P7 - classlc LPLC
C104:P4 - Lurope 2011 CuLbreak
832 cases of PuS, 32 deaLhs
8oLh adulLs and chlldren aecLed
SLomach cramps, vomlung, dlarrhea (bloody), low fever
hup://www.cdc.gov/ecoll/2011/ecollo104/
Atyp|ca| nUS
Also a mlcroanglopaLhlc hemolyuc anemla wlLh
LhrombocyLopenla, organ dysfuncuon
Ceneuc predlsposluon Lo hyperacuvauon of
complemenL sysLem
8are, descrlbed more oen ln chlldren
llare/presenLauon of dlsease wlLh nonspeclc
lnfecuon prodrome or sLress, noL necessarlly
dlarrhea
Conslder ecullzumab - anu C3 monoclonal anubody
- uaLa - lndlvldual case reporLs
norrls, naL 8ev nephrol, 2012, 8:622
11 vs. 11-nUS vs. Atyp|ca| nUS
11: AuAM1S-13 declency medlaLed
LreaL wlLh plasma exchange
PuS and 11-PuS: Shlga-Loxln medlaLed
1reaLmenL supporuve ln classlc PuS ln CPlLu8Ln (renal fallure/
lnsumclency, bloody dlarrhea, LhrombocyLopenla and hemolyuc
anemla). Pemodlalysls may be requlred
11-PuS ln AuuL1S oen ln Lhe absence of hemorrhaglc dlarrhea,
-LreaLmenL: plasmapheresls
aPuS: congenlLal defecL ln complemenL
Chlldren > adulLs
Conslder ecullzumab
hup://l.lmgur.com/v8M0v.[pg?7660 Accessed 6/2/2013
?ou are called for consulL on a 78 yo man Laklng warfarln for
aLrlal brlllauon who complalned of brulslng. Pe has
shorLness of breaLh. Pe has no eplsLaxls, hemaLemesls,
hemaLochezla. P8 90's, noL hypoLenslve. 1here are crackles
on lung exam and 2+ perlpheral edema. Pls warfarln was
held for 1 day. Admlsslon ln8 7.1 now 6.8, hemoglobln has
decreased from 12.3 aL basellne Lo 11.9 g/dL.
Was lnlual approach Ck?
WhaL should be done now?
A) 10 mg lv vlLamln k + 3 ml/kg ll
8) 10 mg lv vlLamln k alone
C) 10 - 13 mg/kg ll alone
u) acuvaLed lvll slngle dose
L) 2 mg oral vlLamln k
Iresh Irozen |asma: Ind|canons
CorrecL lnadequaLe hemosLasls ln bleedlng pauenL
LlevaLed 1/ln8, a11 (>1.3 - 2.0 x normal)
nC1 ln a pauenL wlLh facLor declency (hemophllla)
Wherever posslble, admlnlsLerlng speclc facLor replacemenL should
be rsL prlorlLy
rophylacuc or prlor Lo lnvaslve procedure
Plgh rlsk of bleedlng compllcauons based on planned surgery
Anu
CoagulopaLhy (ln8 > 1.3)
C8
rlor Lo any lnvaslve procedure when severe coagulopaLhy
ln8>2.0 - 2.3
Dose and D|mcu|nes w|th II
- 10 - 13 ml / kg - resLores coagulauon
facLors Lo 20-30 normal
1 unlL of ll Lyplcally 230 - 300 ml
Managlng volume ls lmporLanL
ln pauenLs wlLh ln8 1.1 Lo 1.83 who recelved ll,
less Lhan 1 had correcuon of 1 - ln8 and only
13 had 1-ln8 correcLed half-way Lo normal
Abdel-Wahab, 1ransfuslon, 2006, 46:1279-1283
Ind|canons and Dos|ng for Cryoprec|p|tate
Correcuon of hypobrlnogenemla ln crlucally lll
pauenLs aL rlsk for hemorrhage
Masslve Lransfuslon
Consumpuve coagulopaLhy (ulC)
1argeL and monlLorlng
Serum brlnogen > 100 mg/dL
lnlual uose
3 - 10 pooled unlLs
SubsequenL doses should be based on
measuremenLs of serum brlnogen
D|ssem|nated Intravascu|ar Coagu|anon
non-locallzed clomng acuvauon / Lhrombosls followed by
sysLemlc brlnolysls. 8esulL ls LhrombocyLopnela and
depleuon of clomng enzymes and brlnogen.
Causes
Masslve ussue ln[ury
vascular endoLhellal ln[ury
Shock
Amnlouc uld or faL embollsm
1raumauc braln ln[ury
Mallgnancy
Severe lnfecuon
DIC C||n|ca| and Lab Ieatures
ulsungulshed from 11 (whlch also has
schlsLocyLes) by abnormal coags, brlnogen and
cllnlcal scenarlo
Can have Lhrombosls (assoclaLed wlLh
mallgnancy)
ulC Scorlng sysLems
laLeleL counL
roLhrombln ume
llbrlnogen
u-dlmer
Cando, CrlL Care Med, 2006
1reatment |n DIC
1reaL underlylng dlsorder
PeLerogeneous cllnlcal group, general rules problemauc
88C Lransfuslon lf physlologlcally slgnlcanL anemla
rophylacuc blood componenLs
Conslder only lf planned lnvaslve procedure
Acuve Mucosal 8leedlng or Pemorrhage
laLeleL lf <30,000/mm3
CryopreclpuaLe lf brlnogen <100 mg/dl
ll/plasma - ln hemodynamlcally slgnlcanL hemorrhage
slLuauon and severely prolonged a11 (>2-3x normal)
Coumad|n: approach to supratherapeunc INk
no cllnlcally slgnlcanL bleedlng
ln8 < 3 - hold nexL dose, follow
ln8 > 3 - glve 1 - 2 mg oral vlL k
ln8 > 10 or exLreme elevauon - 3 - 10 mg oral vlL k
Any level of ln8 wlLh hemodynamlcally slgnlcanL
bleedlng
10 mg slow lnLravenous lnfuslon vlL k
ll unless conLralndlcauon based on volume sLaLus
Ansell, 2008, ChesL, 133:160S-198S
Nove| Cra| Coag Iactor Inh|b|tors
ulrecLly lnhlblL Lhrombln (dablgaLran), or acuvaLed
facLor x (rlvaroxlban, aplxaban)
lnLenslLy of anucoagulanL eecL noL rellably assessed
by Lradluonal coagulauon umes
uablgaLran - prolongs 11
use noL monlLored wlLh coagulauon LesLs
8leedlng compllcauons can occur
1reaLmenL supporuve
LlmlLed lnformauon on use of proLhrombln complex
concenLraLe
Mlesbach, 1hromb PaemosL, 2012, 108:623
Mass|ve 1ransfus|on
Masslve 1ransfuslon
8eplacemenL of >30 blood volume / 24 hr
8eplacemenL 100 blood volume/12 hr
> 10 u 88C / 24 hours
MonlLor 1, a11, brlnogen and plaLeleL counL every 3 Lo
10 unlLs of blood admlnlsLered
8lood producLs glven based on resulLs of Lesung
ln8 a11 >1.3-2, plL <100,000, brlnogen < 100 mg/dL
roLocols for replacemenL of x unlLs of 88C Lo ? unlLs
plaLeleLs Lo Z unlLs of ll" - may be beneclal ln masslve
Lrauma pauenLs, buL noL valldaLed ln general medlcal
populauon.

Mcuanlel, ! Am Coll Surg, 2013, 216:1103
kecomb|nant Iactor VIIa
Approved lndlcauon for LreaLmenL of bleedlng
hemophlllac pauenLs wlLh anubody lnhlblLors of
facLor vlll or lx or ln congenlLal vll declency
MeLa-analysls and sysLemauc revlews:
C label lndlcauons: no beneL for morLallLy and
lncreased rlsk for Lhromobosls
?ank, 2011, Ann lnLern Med, 134:329
Lln, Cochrane uaLabase SysL 8ev, 2011: Cu003011
MorLallLy 8lsk ulerence
for o-label lacLor vlla
lndlcauons
1hromboembollsm 8lsk
ulerence for o-label lacLor
vlla lndlcauons
?ank, 2011, Ann lnLern Med
134:329
1he 8ouom L|ne
erslsLenL LhrombocyLopenla ls a negauve prognosuc
lndlcaLor
l1 - lsolaLed LhrombocyLopenla
11 and PuS - mlcroanglopaLhlc hemolyuc anemla
ulC - comblned coagulopaLhy
uose of ll - 13ml/kg
noL all warfarln levels requlre lnLravenous vlL k
MonlLor coag's and plaLeleL counL ln masslve Lransfuslon
Adhere Lo approved lndlcauon for facLor vlla