Bleeding

disorders

Vascular Clotting factor

Platelet disorders DIC
abnormalities abnormalities
 BV Injury
Tissue
Neural Factor

Blood Vessel Platelet Coagulation

Constriction Activation Activation
Primary hemostatic plug
Reduced Plt-Fusion Thromibn,
Blood flow Fibrin

Stable Hemostatic Plug

 Hemostasis
Platelets &vessel wall Coagulation &
(Primary hemostasis) thrombosis
(Secondary
Thrombocytopenia hemostasis)
Vonwillibrands disease
Druginducedplateletdysfunction HemophiliaA
HemophiliaB
VitaminKdeficiency
Antiplatelets
Othercoagulationfactors
Aspirin
Deficiency(v,vii,x,xiii,
Thienopyridines(ticlopidine,clopidogrel)
Proteinc,s,antithrombin III
GpIIa/IIIbantagonists(abciximab,eptifibatide,tirofiban)

Anticoagulant
Heparin(UF,LMWH)

Fibrinolytic drugs
STK,Urikinase,TPA
 Primaryvssecondaryhemostasis
Clinical Defects of primary Defects of
manifestation hemostasis secondary
hemostasis

Onset immediate Delayed -hrs/days

site Superficial mucosal Deep joints, muscle,

bleed

Physical finding Petechiae, Hematoma,

ecchymosis hemarthrosis

Treatment immediate, local Require sustain

Measures effective Systemic therapy
response
 DisordersofHemostasis
Vascular disorders
Scurvy,easybruising,HenochSchonlein purpura.
Platelet disorders
Quantitative Thrombocytopenia
Qualitative Plateletfunctiondisorders Glanzmans, von
Willebrand disease
Coagulation disorders
Congenital Haemophilia (A,B)
Acquired VitaminKdeficiency,Liverdisease
Mixed/Consumption: DIC
 HSP/Anaphylactoidpurpura
Selflimitedtypeofvasculitis
Children&youngadults
Purpuric /urticarial rashonextensorsurfaceofarms,legs&
buttocks
Polyarthralgias/arthritis
Colicy abdominalpain
Hematuria (focalglomerulitis)
Coagulationparametersarenormal
Treatment glucocorticoids (symptomatic)
 Thrombocytopenia
Decreased marrow production eg
Marrowaplasia,infiltrationwithmalignantcells,drugs

Splenic sequestration eg
portalhypertension,splenic infiltrationwithtumor
cells,myleloproliferative &lymphoproliferative disorders

Accelerated destruction eg HUS

Immunologicalviral(dengue),bacterialinfection
Drugs,Idiopathic ITP
 Drugscausingthrombocytopenia
Chemothreapeutic agents Carboplatin,alkylating
agents,anthracyclines,antimetabolites
Antibiotic sufonamides,penicillins,cephalosporins
Heparins UF
Antihypertensive thiazide diuretics,ACE inhibitors
Alcohol

Bestproofofdruginducedetiologyisapromptriseinplateletcountwhen
suspecteddrugisdiscontinued.

Treatment stopculpritdrug(recoverwithin710days)
plateletcount<10000&bleeding
glucocorticoids
plasmapharesis/platelettransfusion
 HeparinInducedThrombocytopenia
HIT
Seen in 3-5% of patients treated with unfractionated heparin
thrombocytopenic after 1-2 weeks of Rx
Caused by IgG antibodies against platelet factor 4/heparin
complexes on platelet surfaces
Exacerbates thrombosis, both arterial and venous (in setting
of severe thrombocytopenia)
Antibody binding results in platelet activation and
aggregation.
Rx - cessation of heparin
 Acute ITP
Commoninchildren,followsrecoveryfromviral
exanthem/URTI

Suddenonset&thrombocytopeniaisoftensevere.

60%recoverwithin46wks&>90%within36months

Mechanismisbyformationofimmunecomplexcontaining
viralantigens&formationofantibodiesagainstviralantigens
whichcrossreactswithplatelets&leadtotheirimmunological
destruction
 ChronicITP
Commoninadults(2040yrs) F/M3:1
Insidiousonset&persistforseveralyears
Formationofantiplatelet antibodiessynthesizedinspleen
Sensitizedplateletaredestroyedinspleen
Clinicalfeatures petechiae,hemorrhage,easybrusing,mucosalbleeding
fromgums,malena
Labthrombocytopenia,BFlargeplatelet,
marrownoofmegakaryocyte withlargenonlobulated singlenuclei
Plateletsurvivalsudies lifespan
Coombstestantiplatelet IgG antibody

Treatment
<10%casesrecoverspontaneously
Steroidprednisolone 60mg/dx46wks
Immunosupressive danazole,
azathioprine,cyclophospamide,vincristine,vinblastin,cyclosporin
Splenectomy
IVIg
 ITP
Feature Acute Chronic
Age / Sex Children Adult/Female
Onset Abrupt Gradual
Predisposing Viral infection/ -
Factors vaccine
Duration <2 months >6mnoths
Pathogenesis - IgG against
Platelet GP
Peripheral smear Thrombocytopenia Same
& Giant PLTS
Bone marrow Normal or Same
Megakaryocytes
 ITP
Feature Acute Chronic
Tests Prolonged BT & Same
Normal PT & PTT
Complication (most Intracranial bleed Same
dangerous)
Clinical course Spontaneous No
remission
Treatment
PLT. Transfusion If <20,000 If <50,000
Splenectomy No Yes (refractory
cases)
ThromboticThrombocytopenicpurpura(TTP)
Fulminant oftenlethaldisorderinitiatedbyendothelialinjury&subsequentrelease
ofprocoagulant factorseg Vwf
Causepregnency,metastaticcancer,mitomycin C,Chemothreapy,HIV,drugs like
ticlopidine
Clinicalfeature pentard
hemolyticanaemia
thrombocytopenia
neurologicalfinding
renalfailure
fever
Treatment
Removal/correctppt factors
Exchangetransfusion/intensiveplasmapharesis
Infusionoffreshfrozenplasma
Mostpatientsurvivea/cillnessrecovercompletelywithnoresidualrenalor
neurologicaldisease
 Hemolyticuremicsyndrome(HUS)
Diseaseofinfancy/earlychildhood
Clinicalfeature Tetrad
fever
thrombocytopenia
microangiopathic hemolyticanemia
a/crenalfailure
Onsetisprecededbyminorfebrileviralillness
EpidemicrelatedtoinfectionE.coli (0157H7)
hasbeendocumented
Treatment
Notherapyeffective
Symptomatic dialysisfora/crenalfailure
5%mortalityinchildren
1015%developCRF
 ThromboticMicroangiopathies

HUS Feature TTP

Absent Neurological Prominent

symptoms
Prominent Acute Renal Failure Less prominent
Children Age Adults
Infection Cause Genetic
( E.coli O157 : H7) (vWF metalloprotease-
ADAMTS 13)
deficiency
Supportive Rx. Plasma Exchange

Good in children Prognosis Better with plasma

Bad in adults exchange
 VonWillibrandsdisease
Mostcommoninheritedbleedingdisorder
vonWillibrand factorheterogeneousmultimeric plasma
glycoprotein
Facilitatesplateletadhesion
PlasmacarrierforfactorVIII(antihemophylic factor)
NormalplasmavWF levelis10mg/l
ModestreductioninplasmavWF conc.decreasesplatelet
adhesion&causeclinicalbleeding
Mildcasesbleedingoccursonlyaftersurgeryortrauma
Moreseverelyaffectedpatientshavespontaneousepitaxis or
oralmucosal,git,genitourinary bleeding
 Variants
Type I Type II Type III

Incidence Most Less Least

common common common
inheritance AD AD AR

vWF <50%

RC activity

Multimer N A
pattern
 Lab
BT Prolonged
NPlateletcount
ReducedplasmavWF concentration
Defectiveplateletaggregationwithristocetin.
ReducedfactorVIIIactivity
 Treatment
FactorVIIIconcentrateinfusion(cryoprecipitate)
Duringsurgery/traumafactorVIIIconc.InfusiongivenBDX2
3days
Minorbleedingrespondstosingleinfusion
Desmopressin effectiveonlyintypeI, canbegiven
intravenouslyorbyanintranasalspray(1.5mg/mL).Thepeak
activitywhengivenintravenouslyisapproximately30min,
whileitis2hwhengivenintranasally.Theusualdoseis0.3
g/kgintravenouslyor2squirts(1ineachnostril)forpatients
>50kg(1squirtforthose<50kg).