8/19/2019 tpeniad

1/23

1

Thrombocytopenia

What we will cover today:Normal platelet production and survival

Thrombocytopenic bleedingApproach to thrombocytopeniaITP

DICCases

April 16, 2 1, Dr! D!"ee

8/19/2019 tpeniad

2/23

2

Thrombocytopoiesis

PLURIPOTENTSTEM CELL

COMMITTEDPROGENITOR

CELL

RECOGNIZABLEBONE MARROW

PRECURSOR CELL

MATUREBLOODCELL

myeloblastmonoblast

pronormoblast red cellneutrophilmonocyte

basophil

platelet

CFU-Baso

CFU-Eos

CFU-GMBFU-E/CFU-E

eosinophil

pre-T

pre-B

myeloidproge itor

!ell

lymphoid

lymphoblast

lymphoblast

T-cell

B-cell& plasma cell

MI"EDPROGENITOR

CELL

C#U$Meg mega%aryo!ytepl&ripote t'tem !ell

8/19/2019 tpeniad

3/23

3

Platelet formation

megakaryocyte formation ofdemarcationmembranes

platelets

(pro)platelets

8/19/2019 tpeniad

4/23

4

Platelets in the circulation:Influx, efflux, and redistribution

CIRCULATINPLAT!L!T"

"PL!!N

#!"TRUCTI$Nor R!%$&AL

PR$#UCTI$N

platelet count( ) thrombopoietin

!"#

$"#

8/19/2019 tpeniad

5/23

5

Thrombopoietin

increased

normal

t(rom)o!ytope ia

*TPO+ ,ree

*TPO+total normal

normal

ormal platelet !o& t

platelet

T%

plasma

8/19/2019 tpeniad

6/23

6

Thrombocytopenic bleedin'

#is$ o% bleedingplatelet countcause o% thrombocytopenia

comorbid diseasedrugs

Clinical mani%estationspetechiaepurpura, ecchymoses

mucosal bleedingmenorrhagiaintracranial bleeding

Ris( of thrombocytopenichemorrha'e in A%L

)

*)

+)

)

-)

) +) -) .) /) *))

Platelet count 0x *)123L4

5 d a y s 6

i t h ' r o s s

h e m o r r

h a ' e

8/19/2019 tpeniad

7/237

Approach to thrombocytopenia

' aplasia' in iltration' ine ecti e me*a+aryopoiesis e*, M .' selecti e impairment o plateletproduction

Causes o splenome*aly' in ection' in lammation' con*estion' mali*ancy' red cell disorders' stora*e diseases

' immune auto-immune ( T%0 .1E dru*s in ections allo-immune' non-immune sepsis C0 TT%0 2U. hypertensi e disorders o pre*nancy

loo+ or splenome*aly bone marro3 in esti*ationre ie3 meds

loo+ or underlyin* disordersre ie3 meds

T-ROMBOC.TOPENIA

r&le o&t p'e&dot(rom)o!ytope ia

SE/UESTRATION PRODUCTION DESTRUCTION

8/19/2019 tpeniad

8/238

ITP

idiopathic autoimmune plateletdestruction

&1 cause o% isolated thrombocytopenia inother'ise healthy young personsa diagnosis o% e(clusion

8/19/2019 tpeniad

9/239

ITP: Clinical features

occurs in any age or se(, but typicallyyoung %emale

can be preceeded by viral in%ectionsigns and symptoms depend on plateletcountonset usually insidious

8/19/2019 tpeniad

10/23

10

ITP: Laboratory features

ITP I) A DIA*N+)I) + -.C"/)I+Nno sensitive and speci0c test %or ITP

isolated thrombocytopeniaincreased Pnormal PT, PTT

bone marro' investigation not essential instraight%or'ard cases

8/19/2019 tpeniad

11/23

11

ITP: TreatmentPatient is not bleedin'

plt 3 4 5 #( not indicatedplt 2 4 5 #( usually not needed, monitor

closelyplt 7 2 5 #( indicated 'ith one or more o%5prednisoneI I*

anti D i% #h possplenectomy i% relapsing severe ITP

8No role %or prophylactic platelet trans%usion, even i% plt 9 :

8/19/2019 tpeniad

12/23

12

ITP: TreatmentPatient is bleedin'

or serious bleeding 8eg! CN),retroperitoneal, *I:

Prednisone and I I* Trans%use plateletsconsider urgent splenectomyProvide other supportive;resuscitative care as needed

8/19/2019 tpeniad

13/23

13

ITP: Pro'nosis

Children5 usually permanent remission

Adults5 usually relapsing 8chronic ITP:, butcourse is relatively benign!

8/19/2019 tpeniad

14/23

14

#isseminated Intra7ascularCoa'ulation 0#IC4

DIC is characteri

8/19/2019 tpeniad

15/23

15

Causes of #IC

In%ection bacterial sepsis, viralin%ections

Neoplasm A ", adenocarcinoma+bstetrical disorders retained dead %etus,abruption, etc

Trauma;surgery brain in=ury, crush, burns, etc!

+thers acute hemolytic trans%usionreaction, etc!

8/19/2019 tpeniad

16/23

16

depletion of clotting factorsprolonged PT, PTT

increased FDP and D-dimer

thromboctyopenia (consumption)

LA8$RAT$R9%ANI !"TATI$N"

microangiopathic hemolytic anemia

decreased fibrinogen

depletion of physiologic anticoagulants

tissue factor release

activation of intrinsicpathway of coagulation

(systemic thrombingeneration)

generali ed intravascular fibrin deposition

underlying disorder

activation offibrinolytic system(systemic plasmin

generation)

PAT;$P;9"I$L$ IC!&!NT"

Pathophysiolo'y of #IC

hemorrhage

thrombosis!infarction

CLINICAL%ANI !"TATI$N"

8/19/2019 tpeniad

17/23

17

Treatment of #IC

treat the underlying diseasereplacement therapy

cryoprecipitatePplatelet concentratepac$ed red cells

consider additional pharmacologic therapycontroversial or investigational agents> AT, APC, PC concentrate, heparin, anti0brinolytic

agents!

8/19/2019 tpeniad

18/23

18

The most important stuff toremember:

Approach to thrombocytopeniaITP diagnosis and management

?hen to 'orry about a lo' platelet count

8/19/2019 tpeniad

19/23

19

Thrombocytopenia: Case *

A previously healthy 23 year old female competitive lacrosse player presents to your office with a three day history of increased ruisin! and petechiae" #er only medications are napro$en and anoral contraceptive" %hysical e$am shows petchiae on the le!s andseveral small ruises on the e$tensor surfaces"

&eu'ocytes ($ 10 9)&* 6"8 +4"0 , 11"0-#emo!lo in (!)&* 130 +120,160-

./ (f&* 87 +80 , 100-%latelet count ($ 10 9)&* 11 +150 , 450-.% (f&* 12.5 +7"4 ,10"4-

8/19/2019 tpeniad

20/23

20

Thrombocytopenia: Case *

#ow do you approach this pro lem dia!nostically

#ow you mana!e this patient and what do you advise hera out her activities and medications

8/19/2019 tpeniad

21/23

21

Thrombocytopenia: Case +A / / comes ac' on a 75 year old man who is new to your practice"

&eu'ocytes ($ 10 9)&* 3.6 +4"0 , 11"0-#emo!lo in (!)&* 127 +140 , 180-./ (f&* 101.5 +80 , 100-%latelet count ($ 10 9)&* 56 +150 , 450-.% (f&* 8"1 +7"4 ,10"4-

eticulocytes ($ 10 9)&* 86 +18 , 94-

eutrophils ($ 10 9)&* 1.3 +2,7"5"0-

&ymphocytes ($ 10 9)&* 1"6 +1"5,4"0-.onocytes ($ 10 9)&* 0"7 +0"2,0"8-

osinophils ($ 10 9)&* 0 +0,0"7-asophils ($ 10 9)&* 0 +0,0"1-

o platelet clumps are seen on the peripheral lood film"

8/19/2019 tpeniad

22/23

22

Thrombocytopenia: Case +What is the differential diagnosis?

12 folate deficiencyhypersplenismalcoholmedicationsmyelodysplasiaother one marrow patholo!y

How do you sort this out?

tain a history and e$amine the patient"ltrasound of the a domen (spleen si e*"

:erum 12 / folate one marrow investi!ation"

8/19/2019 tpeniad

23/23

23

Thrombocytopenia

What we hopefully have covered today:Normal platelet production and survival

Thrombocytopenic bleedingApproach to thrombocytopeniaITP

DICCases