Coagulation course

( 5 lectures)

1: Haemostasis & role of platelets

2: Haemostasis, role of coagulation proteins
3: Bleeding disorders/ role of platelets & blood
vessels
4: Bleeding disorders due to coagulation defects
5: Thrombophilia
 Hemostasis
Components involved:

1: Platelets
2: Coagulation Factors
3: Blood Vessels
4: Fibrinolysis
5: Coagulation Inhibitors ( anticoagulants)
Coagulation /Haemostatic Disorders

1. Bleeding tendency disorders

2.Thrombotic tendency disorders

Abnormal bleeding results from:
1: vascular disorders

2: platelet disorders ( number / function)

3: defective coagulation
Vascular Disorders

A group of conditions
characterized by easy bruising
and spontaneous bleeding from
small blood vessels
Vascular Disorders
Bleeding is mainly into the skin causing
petechiae or ecchymoses
Vascular Disorders
Inherited
Hereditary Hemorrhagic Telangiectasia (HHT)
Collagen (eg., Ehlers-Danlos, Ostogenesis
Imperfecta, Marfans)
Acquired
Vasculitis
Scurvy, etc.
Acquired Vascular Disorders
* Simple bruising that occurs in women of

child-bearing age
* Senile purpura
* associated with infections
* Henoch-Schonlein purpura
* Vit-C def (scurvy)
Vascular disorders – Senile Purpura
Bruising and
purpura in hand
and arm of an
elderly patient due
to poor
vasculature
Vit C deficiency
Peri-follicular petechiae
Thrombocytopenia = reduced platelet number

Normal platelet count 150-400 x 109/L

Hemorrhages are grouped roughly according to size
Petechiae 1 to 2 mm in Skin Mucous Membranes or serosal
Surfaces ( Due to Increased intravascular Pressure, Low
Platelets Count or Function and Clotting Factors Deficits)
Purpura Larger (=> 3 mm)hemorrhages (As Above
Causes+trauma, vasculitis &increased Vascular Fragility eg
amyloidosis
Ecchymoses Larger (1 to 2 cm) subcutaneous hematomas
(bruises) usually due to trauma
Larger accumulation of blood in body cavities are called
hemothorax, hemopericardium or hemarthrosis depending on
location
e
Causes of Thrombocytopenia

I: Decreased production

•Leukemias

•Myeloproliferative disorders

•Aplastic anemia

•Drugs (e.g. chemotherapy)

Bone marrow in
myelofibrosis
Infiltration
of bone
marrow
with
malignancy
Treat with

Platelet
transfusions
Causes of thrombocytopenia

II: Increased destruction / consumption

Autoimmune ( ITP)
Disseminated Intravascular Coagulation (DIC)
Thrombotic Thrombocytopenic Purpura (TTP)
Viral infections
Neonatal alloimmune purpura
Post transfusion purpura
Immune (idiopathic)
Thrombocytopenic
Purpura = ITP
Immune Thrombocytopenic Purpura
(ITP)

Pathophysiology: auto-antibodies
produced by the body that attack and
destroy platelets
 ITP

Acute Chronic
 Acute ITP

• In children
• Follows infection / vaccination
• Most cases resolve spontaneously, 5-10%
may become chronic
• No treatment needed
 Chronic ITP

* A common disorder
* Mostly in women (15 – 50 yrs)
* May be part of other diseases e.g. SLE, Evan’s
syndrome, CLL, HIV ..
* Runs a chronic course
ITP - Signs & symptoms :
Skin & mucous membrane bleeding
[nose (epistaxis) and mouth bleeds]

Menorrhagia in women

Intracranial hemorrhage is rare (functionally active

platelets)
Immune Thrombocytopenic purpura in a patient showing acute
purpuric rash - note tiny lesions (petechiae), small purple spots
(purpura) and larger coalescences
Diagnosis of ITP
1: low plt count
Diagnosis of ITP
2: normal / increased No. of megakaryocytes in BM
ITP - Rx:
Observation
Steroids
I.V. immunoglobulins
Splenectomy
Immunosuppressive agents
Disseminated intravascular coagulation (DIC)
Pathophysiology:

Release of procoagulant material into the circulation

or
endothelial cell damage generalized activation
of the coagulation and fibrinolytic pathways

widespread fibrin deposition in the circulation, and

consumption of platelets and coagulation factors with
increased fibrinolysis

Microvascular thrombus can lead to organ damage esp.

kidneyes, lungs and brain
DIC - Pathophysiology
DIC is a disease that is caused by a large

number of different conditions which lead

to the generation of intravascular thrombin

with consequent consumption of the

cellular (plts) and humoral (coag. prs.)

components of the hemostatic system

Causes of DIC
•Shock
•Metastatic adenocarcinoma
•Sepsis
•Viremia
•Major intravascular hemolysis
•Obstetric complications (eg dead fetus,
amniotic fluid embolism...)
•Snake bites
•Massive trauma
•Acute brain injury
•Acute promyelocytic leukemia (M3)
 Laboratory abnormalities in DIC

Thrombocytopenia ( plts)
Prolonged PT, APTT, TT,
Raised D-dimer ( or FDP’s)
Reduced fibrinogen
Blood film: shows microangiopathy
(fragmented red cells)
Treatment of DIC

•First and most important: TREAT THE

UNDERLYING CAUSE

•Replace consumed factors and platelets with

blood component therapy
•Heparin - ~ 5% of cases (eg., acute
promyelocytic leukemia, organ ischemia,
amniotic fluid embolism, etc.)

antithrombin & Protein C concentrates

TTP, showing fragmented red cells
Management of TTP:
The mainstay of treatment is plasma exchange
with FFP or cryoprecipitate – poor plasma
Qualitative Platelet Defects
( Plt dysfunction)

normal platelet count with abnormalities of

adhesiveness and aggregation.

Diagnose with bleeding time, platelet

aggregometry and more sophisticated
studies
 Qualitative Platelet Defects
( Plt dysfunction)

AQUIRED

INHERITED
HIT
Heparin Induced
Thrombocytopenia
 Qualitative Platelet Defects
( Plt dysfunction)
INHERITED:
–Thrombopathies (e.g. storage
pool disease)
–Glanzmans Thrombasthenia
(abnormal or absent GP IIb-
IIIa)
–Bernard Soulier Syndrome
(abnormal or absent GP Ib-IX)
Summary:

Bleeding
Abnormalities in

Coag. Platelets Blood

proteins vessels

Function
Number