DR SHWE SIN

FMHS
 State the underlying aetiology of abnormal
bleeding.
State the laboratory tests used to diagnose
bleeding abnormality.
Describe aetiology, pathogenesis, clinical
features and diagnosis of ITP.
State the common congenital and acquired
coagulation disorders.
Describe the aetiology, pathogenesis, C/F
and laboratory findings of DIC.
This may result from:
1) Vascular disorders (Blood vessel defects)
2) Platelets defect
Thrombocytopenia (Reduction in platelet
count)
Thrombocytopathy (Defective platelet
function)
3) Coagulation factors defect
 Platelet/Vessel Coagulation
wall diseases diseases
Mucosal Common Rare
bleeding
Petechiae Common Rare
Deep Rare Characteristic
haematoma
Bleeding from Persistent Minimal
skin cuts
Sex of patient Equal > 80 % males
 Bleeding time (BT) (Abnormal in platelet
defects)
1) Ivy method
2) Duke method
Clotting time (CT)
Platelet counts
Thrombin time (TT) (F I)
Prothrombin time (PT) (F I, II, V, VII, X)
Activated partial thromboplastin time (APTT)
(F I, II, V, X, VIII, IX, XI, XII)
 Heterogeneous group of conditions (inherited
or acquired)
Characterized by easy bruising and
spontaneous bleeding from small vessels
The abnormality is either in the vessels or in
the perivascular connective tissues
Not severe in most cases
The bleeding time and other tests are usually
normal
 Abnormal bleeding can be associated with
Thrombocytopenia or abnormal platelet
function (Thrombocytopathy)

Characterized by spontaneous skin purpura,

mucosal haemorrhage and prolonged
bleeding after trauma
 Reduction in platelet count is termed thrombocytopenia
Normal value: 150-400 x 109/L

Causes of Thrombocytopenia
I. Failure of platelet production
Selective megakaryocyte depression(drugs, chemicals, viral
infections, congenital)
Part of general bone marrow failure (cytotoxic drugs, leukemia,
AA, MDS etc.)
II. Increased consumption of platelets
Immune cause (ITP)
DIC
TTP
III. Abnormal distribution of platelets
Splenomegaly
IV. Dilutional loss (massive transfusion)
 Divided into chronic and acute forms
 Relatively common disorder
Highest incidence in women aged 15-50
years
The most common cause of
thrombocytopenia without anaemia or
neutropenia
May be associated with SLE, HIV infection, H.
pylori infection, CLL, Hodgkin lymphoma or
AIHA
Pathogenesis

Due to formation of platelet auto antibodies

(usually IgG) result in premature removal of
platelets by macrophages of spleen
Platelet lifespan is reduced to a few hours
(normal- 7-10 days)
Megakaryocyte count becomes increased
Clinical Features

Often insidious onset

Tends to relapse and remit spontaneously
Petechial haemorrhage
Easy bruising
Menorrhagia
Mucosal bleeding (epistaxes, gum bleeding)
Intracranial haemorrhage (rare)
Diagnosis

Platelet count- reduced (usually 10-

100x109/L)
Hb% usually normal
White cell count- usually normal
Blood film- reduced numbers of platelets
those often being large
Bone marrow- increased megakaryocytes
Other test- demonstration of antibodies
 Most common in children
75 % of patients follows vaccination or an
infections(chickenpox, infectious
mononucleosis)
Spontaneous remission are usual
But the disease may become chronic (lasting
>6 months)
Morbidity and mortality is very low
 Deficiency of either any coagulation factors

Divided into hereditary causes and acquired

causes

In hereditary causes, haemophilia A ,

haemophilia B and von Willebrand disease
(VWD) are the most frequent
 Most common of hereditary clotting factor
deficiencies (factor VIII deficiency)
Sex-linked
1/3 of patients have no family history and
result from recent mutation
5 times more common than haemophilia B
Clinical features

Profuse haemorrhage after surgery

(circumcision)
Joint and soft tissue bleeding
Excessive bruising
Recurrent painful haemarthroses and muscle
haematoma in severe cases and can lead to
joint deformity and disability
GIT haemorrhage
Intracranial haemorrhage (rare but fatal)
Laboratory findings

Prothrombin time (PT) normal

Bleeding time- normal
Activated partial thromboplastin time
(APTT)- prolong
Factor VIII clotting assay can be done
 Also known as Christmas disease and it is factor
IX deficiency
Identical to those of haemophilia A
The two disorders can only be distinguished by
specific coagulation factor assays

Laboratory findings
Prothrombin time (PT) normal
Bleeding time- normal
Activated partial thromboplastin time (APTT)-
prolong
Factor IX clotting assay can be done
 Due to either a reduced level or abnormal
function of von Willebrand factor (VWF)
VWF is produced from endothelial cells and
megakaryocytes
It promotes platelet adhesion and is also a
carrier molecule for factor VIII
Three types have been described (Type 1, 2 &
3)
Clinical features
Mucous membrane bleeding
Excessive blood loss from cuts and abrasions
Operative and post-traumatic haemorrhage

Laboratory findings
Bleeding time test- abnormal
F VIII/VWF binding assay- low
APTT- prolong
VWF level- low
Platelet count usually normal
 More common than inherited
disorders
Unlike the inherited disorders,
multiple clotting factor
deficiencies are usual
Common causes- Vitamin K
deficiency, liver diseases, DIC
 May present in the newborn (haemorrhagic
disease of the newborn) or in later life
Deficiency caused by inadequate diet,
malabsorption or inhibition by drugs
(warfarin)

Laboratory findings
PT prolong
APTT - prolong
 Multiple
haemostatic
abnormalities contribute to a
bleeding tendency

Mayexacerbate haemorrhage
from oesophageal varices
Causes
Biliary obstruction leads to impaired vitamin
K absorption (decreased synthesis of factors
II, VII, IX and X).
In severe cases, reduced levels of factor V,
fibrinogen (factor I) and increased amount of
plasminogen activator
Thrombocytopenia (reduced thrombopoietin
production)
Hypersplenism (portal hypertension)
DIC may be related
 Widespread inappropriate
intravascular deposition of fibrin
with consumption of coagulation
factors and platelets causing
widespread endothelial damage or
platelet aggregation.
I. Infections (Gram (-) ve infections)
II. Malignancy (Adenocarcinoma, AML M3)
III. Obstetric complications (50%)
IV. Hypersensitivity reactions
V. Widespread tissue damage
VI. Vascular abnormalities
VII. Miscellaneous (Heat stroke, snake bite, liver
disease)
 DIC may be initiated by widespread
endothelial damage and collagen exposure
(e.g endotoxaemia) (OR) Increased tissue
factor release into circulation from
damaged tissue leading to increased
formation of thrombin (OR) Entry of
procoagulant material into circulation (e.g.
amniotic fluid embolism, mucin)
activate coagulation cascades
 Increased amounts of fibrin coagulation
factors defect
Then intense fibrinolysis FDP+++
Finally, widespread platelet aggregation &
increased consumption of coagulation factors
leading to thrombocytopenia and bleeding
problems

Endothelial damage/ Increased tissue factor/

Procoagulant material Thrombus formation
Bleeding (because of excessive usage of
platelets & coagulation factors) & FDP +++
 Usually dominated by bleeding (venepuncture
sites or wounds)
Generalized bleeding (GIT, oropharynx, lungs,
urogenital tract, vaginal bleeding)
Skin lesions
Renal failure
Gangrene of the fingers or toes
Cerebral ischaemia
 Platelet count- low
Fibrinogen concentration- low
Thrombin time (TT)- prolonged
Fibrin degradation products (FDP)(D-dimers)-
high
PT- prolonged
APTT prolonged
Peripheral blood film- Microangiopathic
haemolytic anaemia (mechanical trauma of
red cells)
 Essential Haematology (A.V. Hoffbrand and
P.A.H.Moss), 6th Edition
Robbins Basic Pathology, 9th Edition