BLEEDING

DISORDERS
(HEMORRAGIC DIATHESIS)

DEFINITION
A

group of disorders characterized by

defective homeostasis with abnormal
bleeding.

The

tendency to bleed may be

spontaneous in the form of:
Small hemorrhages
Trauma
Surgical procedure

CAUSES
Platelet
Abnormaliti
es

Coagulatio
n Factors

Vascular
Abnormaliti
es

Thrombocytope
nia

Platelet
Abnormalities

Thrombocytosis

Defective
platelet
function

1. THROMBOCYTOPENIA
DEFINITION
A reduction in the
peripheral blood
platelet count below
the lower limit of
normal i.e. below 150
000 / l

1. THROMBOCYTOPENIAS
Associated

with abnormal bleeding that

includes:
Spontaneous

skin purpura
Mucosal hemorrhages
Prolonged bleeding after trauma

However,

spontaneous hemorrhagic
becomes clinically evident only after
severe depletion of platelet count to level
below 20 000 / l

CAUSES OF THROMBOCYTOPENIA
1. IMPAIRED PLATELET PRODUCTION
a) Generalized bone marrow failure
e.g. Aplastic anemia, leukemia, megaloblastic anemia, marrow
infiltrations
b) Selective suppression of platelet production
e.g. Drugs (anticancer drugs, heparin, diclofenac), alcohol intake.
2. ACCELERATED PLATELET DESTRUCTION
a) Immunologic thrombocytopenia
e.g. ITP, neonatal and post-transfusion
b) Increased consumption
e.g. DIC, TTP, giant hemangiomas, microangiopathic hemolytic
anemia.
3. SPLENIC SEQUESTRATION
Splenomegaly
4. DILUTIONAL LOSS
Massive transfusion of old stored blood to bleeding patients.

DRUG-INDUCED
THROMBOCYTOPENIA
Drugs

can induce thrombocytopenia

through:
I.
II.

Direct effects on platelets

Secondary to immunologically mediated
platelet destruction

Associated

with many commonly used

drugs:
.Chemotherapeutic

agents

.Antibiotics
.Drugs

used in cardiovascular diseases

.Diclofenac
.Heparin

DRUG-INDUCED
THROMBOCYTOPENIA
HEPARIN-INDUCED
THROMBOCYTOPENIA

Is
i.
ii.

distinct from other drugs because:

Thrombocytopenia is not so severe to fall to level
< 20 000/l
Not associated with bleeding but instead are more
prone to develop thrombosis

Mechanism:
Formation
of Ab
against (PF4)-heparin
complex
Occurs in a small

Activates
the
endothelial
cells

Initiates
thrombus
formation

proportion of cases after the

patient has received heparin for 5-10 days.

IMMUNE THROMBOCYTOPENIC
PURPURA (ITP)
Characterized by:
I.
Immunologic destruction of platelets
II. Normal or increased megakaryocytes in the
bone marrow

A. BLOOD
FILM

B. BONE
MARROW

IMMUNE THROMBOCYTOPENIC
PURPURA (ITP)
ACUTE
ITP
Self-limited

disorder
Most frequently in children recover from:
viral

illness.
an upper respiratory illness.
Onset:

Sudden and severe

thrombocytopenia
Recovery: a few weeks to 6 months

IMMUNE THROMBOCYTOPENIC
PURPURA (ITP)
Mechanism
Formation of
immune
complexes
containing viral
antigens
Cross-react
with platelets
Formation of
antibodies against
viral antigens

Immunologic
destruction

IMMUNE THROMBOCYTOPENIC
PURPURA (ITP)
CHRONIC
ITP
More

commonly in adults
Develops insidiously
Persists for several years
Idiopathic
oSimilar

immunologic thrombocytopenia may be

seen in association with SLE, AIDS,
autoimmune thyroiditis

IMMUNE THROMBOCYTOPENIC
PURPURA (ITP)
Pathogenesis

Formation of
anti-platelet
autoantibodi
es (IgG)

Directed
against target
antigens on
the platelet
glycoprotein
(Gp IIb-IIa and
Gp Ib-IX
complex)

Sensitized
platelet are
destroyed
mainly in the
spleen

Rendered
susceptible to
phagocytosis
by cells of the
reticuloendothe
lial system

Clinical Features
Acute ITP
Develop abruptly
Petechial
hemorrhages
Easy bruising
Mucosal bleeding
Nasal bleeding
Bleeding from
gums
Intracranial
hemorrhages

Chronic ITP
Onset may be
insidious
Splenomegaly
Hepatomegaly

THROMBOTIC
THROMBOCYTOPENIC PURPURA
(TTP)
TTP is characterized by:
Thrombocytopenia
Microangiopathic hemolytic anemia
Formation of hyaline fibrin microthrombi
Widespread

presence of microthrombi is
responsible to thrombocytopenia due to:
Increased

consumption of platelets
Microangiopathic hemolytic anemia
Protean clinical manifestations

Pathogenesis
Endothelial
injury

Release of
von
Willebrand
factor and
other
procoagulan
t material

Formation
of
microthrom
bi

Trigger for the endothelial injury comes from

immunological damage by diverse conditions
e.g. pregnancy, metastatic cancer, high-dose
chemotherapy

Clinical Features

Thrombocytope
nia

Microangiopathi
c Hemolytic
Anemia

Fever

Transient
Neurologic
Deficits

Renal Failure

Splenomegaly

Thrombocytope
nia

Platelet
Abnormalities

Thrombocytosis

Defective
platelet
function

2. THROMBOCYTOSIS
Definition:
Causes

platelet count in excess of 4 000 000 / l

bleeding or thrombosis

Types:
i. Primary thrombocytosis (Thrombocytaemia)
ii. Secondary thrombocytosis

2
Thrombocytos
is

Occurs in response to:

.Chronic

infection
.Hemorrhage
.Post-operative state
.Chronic iron deficiency
.Malignancy
.Rheumatoid Arthritis
.Post-splenectomy

Thrombocytope
nia

Platelet
Abnormalities

Thrombocytosis

Defective
platelet
function

3. DEFECTIVE PLATELET
FUNCTION
Suspected in patients who show:
i.
Skin and mucosal hemorrhages
ii. Prolonged bleeding time but a normal platelet
count

HEREDITARY
DISORDERS
A.

Defective Platelet Adhesion

I.

II.

Bernard-Soulier Syndrome: autosomal recessive

disorder with inherited deficiency of a platelet
membrane glycoprotein
von Willebrands disease: defective platelet
adhesion an deficiency of factor VIII

3. DEFECTIVE PLATELET
FUNCTION
B. Defective Platelet Aggregation
I.

Thrombasthenia (Glanzmanns disease) :

failure of primary platelet aggregation with
ADP or collagen due to inherited deficiency in
two of platelet membrane glycoproteins

C. Disorders of Platelet Release Reaction

.Characterized

by normal initial aggregation of

platelets with ADP or collagen.
.Subsequent release of ADP, prostaglandins and
5-HT is defective due to complex intrinsic
deficiencies.

3. DEFECTIVE PLATELET
FUNCTION
A.

ACQUIRED
DISORDERS
Aspirin Therapy

Prolonged

lea

use of aspirin
easy bruising and
d
abnormal bleeding time.
suppresse
Aspirin inhibits the enzyme cyclooxygenase
s
the synthesis of prostaglandins which are
involves in:
Platelet aggregation
Release reaction
Clinically applied in preventing major
thromboembolic disease in recurrent myocardial
infarction

3. DEFECTIVE PLATELET
FUNCTION
B. Others
Associated

with various disorders in platelet

function at different levels.
Include:
i. Uremia
ii. Liver disease
iii. Multiple myeloma
iv. Waldenstrms macroglobulinemia
v. Various myeloproliferative disorders