Hemostatic Disorders

Components of Hemostasis
5 components
Blood Vessels
Platelets
Coagulation
Fibrinolytic System
Inhibitors of Coagulation

Hemostasis:
BV Injury
Tissue
Factor

Neural

Blood Vessel
Constriction

Platelet
Aggregation

Coagulation
Cascade

Primary hemostatic plug

Reduced
Blood flow

Platelet
Activation

Stable Hemostatic Plug

Fibrin
formation

Haemostasis

Red blood cel

Platele

Red blood cel

Platele

Red blood ce
Platel
Von Willebrand fact

Red blood cel

Platele
Von Willebrand facto

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact

Red blood ce
Platel
Von Willebrand fact
Fibrin polym

Red blood ce
Platel
Von Willebrand fact
Fibrin polym

Red blood ce
Platel
Von Willebrand fact
Fibrin polym

Coagulation cascade
Intrinsic system (surface contact)
XII

Extrinsic system (tissue damage)

XIIa

Tissue factor
XIa

XI
IX

IXa
VIII

VIIa

VIIIa
X

Vitamin K dependant factors

VII

Xa
V

Va
II

Fibrinogen

IIa

(Thrombin)
Fibrin

Coagulation Cascade
Intrinsic Path
(XII,XI,IX,VIII)

Extrinsic Path
(VII)

(aPTT)

(PT)

(Factor X)
Common
Path
(V,II)

(TT)

(Thrombin)

Fibrinogen Fibrin

(Fibrin & FDP)

Platelets

Contractile, adhesive, cell fragments

BM Megakaryocytes
Store coagulation factors & enzymes
Surface Binding sites for fibrinogen
Surface Glycoprotein Ags
Glycoprotein IIb/IIIa
Glycoprotein Ib/IX mediates binding of vWF
with platelets
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Disorders of Hemostasis
Vascular disorders
Scurvy, easy bruising

Platelet disorders
Low number or abnormal function

Coagulation disorders
Factor deficiency

Mixed/Consumption: DIC

22

Clinical Features of Bleeding Disorders

Platelet

Coagulation

Skin
tissue
Mucous membranes
(epistaxis, gum,
vaginal, GI tract)

Deep in soft

Petechiae

Yes

No

Ecchymoses (bruises)

Small, superficial

Large, deep

Hemarthrosis / muscle bleeding

Extremely rare

Common

Bleeding after cuts & scratches

Yes

No

Bleeding after surgery or trauma

Immediate,
usually mild

Delayed (1-2days),
often severe

Site of bleeding

(joints,muscles)

23

Platelet
Petechiae, Ecchymoses

Coagulation
Joint bleeding
24

Petechiae & Echymoses -Platelet count

25

Sub Conjuctival Haemorrhage

BLEEDING
DISORDERS

Assessment of Primary Hemostasis

Platelet
Complete blood count (CBC)
Bleeding time
Platelet aggregation study

Blood vessel
Bleeding time

von Willebrand factor (vWF)

Bleeding time
vWF Antigen, vWF: RCO, vWF multimer, FVIII

Bleeding Time
Bleeding time 2-9 minutes
Time taken by a standard skin puncture to stop
bleeding
Prolonged defect in platelet number or function

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Bleeding Time

Thrombocytopenia
Platelet number
Normal platelet count: 150,000 400,000/uL
> 100,000/uL
Bleeding unlikely
< 20,000/uL
risk for spontaneous
bleeding
Must exclude pseudothrombocytopenia

Assess for platelet morphology

Etiology of Thrombocytopenia
Decreased Production
Hypoproliferation

Aplastic Anemia, Amegakaryocytic

thrombocytopenia, infection, toxins,
drugs

Ineffective Thrombopoiesis Infiltrative marrow disease, TAR

Megaloblastic anemia
Increased Destruction
Alloimmune, Autoimmune: ITP, SLE
Immune
Non-immune

DIC, TTP, HUS

Others
Splenic sequestration

Hypersplenism

Dilutional

Massive blood transfusion

Thrombocytopen
ia
Giant
platelet

Bernard-Soulier Syndrome

Pseudothrombocytope
nia

Idiopathic Thrombocytopenic Purpura

(ITP)

ITP
Thrombocytopenia secondary causes are
excluded
destruction of platelets immune
mechanism

Types
Acute - <6mths
Chronic - >6mths

Acute ITP
Most often in children 2 6 yrs
Most often 1 3 wks after viral infection eg; chicken
pox, rubella, CMV, viral hepatitis
Platelet count < 20 x 10 9 / l
Abrupt onset of bleeding
Self limited
Therapy- none
steroids ( severe thrombocytopenia)

Chronic ITP

Adults 20 40 yrs
F: M = 3 : 1
Onset insidious
Antecedent infection unusual
Platelet count 30-60 x 10 9 / l
BT-prolonged
Therapy- Steroids
Splenectomy
Spontaneous remission uncommon

Acute vs Chronic ITP

Acute
Children 2-8yrs
M::F
Usually ellicited
in most cases

Chronic
Adults 20-45yrs
M:F :: 1:3
-

Onset
Duration
Spontaneous
remission

Suddden
2-8 wks
85-90% cases

Insidious
Months yrs
Rare, need
therapy

Platelet Count

<20,000 usually

30-60,000

Age
Sex
H/o preceeding
viral infection

Pathogenesis

Molecular Mimicry:
VZV

Platelet

MHCII

Macrophage
(APC)

1.
Phagocytosis

MHCII

Macrophage
(APC)

2.

Destruction

1.
Phagocytosis

MHCII

Macrophage
(APC)

Infection, Cytokines (e.g. TNF, IFN)

APC Activation
2.

Destruction

1.
Phagocytosis

MHCII

Macrophage
(APC)

Infection, Cytokines (e.g. TNF, IFN)

APC Activation
2.
1.

Destruction

Altered
processing

Phagocytosis

MHCII

Macrophage
(APC)

Infection, Cytokines (e.g. TNF, IFN)

APC Activation
2.
1.

Destruction

Altered
processing

Phagocytosis

Peptides

3.
Macrophage
(APC)

MHCII

Infection, Cytokines (e.g. TNF, IFN)

APC Activation
2.
1.

Destruction

Altered
processing

Phagocytosis

Peptides

MHCII

3.
Macrophage
(APC)

4.
Abnormal
Presentation

Infection, Cytokines (e.g. TNF, IFN)

APC Activation
2.
1.

Destruction

Altered
processing

Phagocytosis

Peptides

CD4+ T cell
Activation
MHCII TcR

3.
Macrophage
(APC)

4.
Abnormal
Presentation
of a platelet
autoantigen

Clinical features
Bleeding into skin, mucous membrane
Menorrhagia adult females
Easy bruising
Intracranial hemorrhage platelet count < 10,000
Splenomegaly & lymphadenopathy rare

Hematological Findings
Platelet count -low
Bone marrow
Megakaryocytic hyperplasia
immature forms+

BT Prolonged
PT & PTT normal

Thrombotic Microangiopathies
Thrombotic Thrombocytopenic Purpura (TTP)
Hemolytic Uremic Syndrome (HUS)

TTP

Fever
Thrombocytopenia
Microangipathic anemia
Renal dysfunction
Seizures

TTP
Endothelial injury bacterial infections
Release of procoagulants & vWF thrombosis
Platelet count 5,000 100,000
PT, APTT-Normal
Platelet transfusion is contraindicated

HUS

Fever
Diarrhea
Microangiopathic HA
Thrombocytopenia
Renal failure

Defective platelet function

Bernard-soullier
syndrome
gp Ib-IX
Glanzmanns
thrombasthenia- IIbIIIa

6/17/15

Thrombocytopenia

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