Thrombocytopenia & Thrombotic

thrombocytopenic purpura

Dr Ahmad Abu al-samen MD

 Thrombocytopenia
 Is characterized by spontaneous bleeding, a prolonged bleeding time,
and a normal PT and PTT. A platelet count of 100,000 cells/μL or less

Relationship between platelet &bleeding

 Normal range 150 – 400,000 X10

 Level above 60 X10 will not causing bleeding
under normal condition
 Level below 20X10will cause
petechiae , mucosal bleeding & post-
traumatic bleeding,
 Level below 5 X10will cause
fatal CNS or GIT hemorrhage
Thrombocytopenia

 Most bleeding tends to occur from small, superficial blood vessels and
produces petechiae or large ecchymoses in the skin, the mucous
membranes of the gastrointestinal and urinary tracts, and other sites.

 Hemorrhages into the central nervous system are a major hazard in

patients with markedly depressed platelet counts.
Causes of Thrombocytopenia
Decreased Production of Platelets :
Generalized disease of bone marrow: 
- Aplastic anemia: congenital and acquired:
  - Marrow infiltration:
- leukemia, disseminated cancer

Selective impairment of platelet production 

- Drug-induced:
alcohol, thiazides, cytotoxic drugs
- Infections: measles, HIV
- infectionIneffective megakaryopoiesis
 - Megaloblastic anemia
- Paroxysmal nocturnal hemoglobinuria
Causes of Thrombocytopenia
Decreased Platelet Survival
Immunologic destruction 
Autoimmune:
immune thrombocytopenic purpura

Isoimmune:
post-transfusion and neonatal:
Drug-associated: quinidine, heparin, sulfa compounds
 Infections: infectious mononucleosis, HIV ,CMV
Nonimmunologic destruction:
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura
Microangiopathic hemolytic anemias
Sequestration
Hypersplenism
Immune thrombocytopenic purpura
(ITP)

Is defined as isolated thrombocytopenia for more than 6 months with no known

associated conditionst hat cause reductions in platelet count

There are two clinical subtypes of primary ITP:

Acute ITP
A self-limited form that is most commonly seen in
children with an equal incidence in boys and girl
 The interval between viral infection & thrombocytopenia is 2 months
 In 75% it follow vaccination or post viral infections as measels ,chickenpox
,infectious mononucleosis.
 It should last less than 6 months
 Spontaneous remission is the usual but in 15% the disease become chronic
Chronic Immune
thrombocytopenic purpura (ITP)
 A relatively common disorder that tends to affect adult
females between the ages of 20 and 40 years
 Most common cause of thrombocytopenia without anemia &
leukopenia

Pathogenisis

 Platelet antibodies adirected against antigens including

GPIIb/IIIa and GPIb-IX. can be identified in 80% of patients
with chronic ITP.
 The spleen is an important site of antiplatelet antibody production
and the major site of destruction of the IgG-coated platelets.
Chronic Immune
thrombocytopenic purpura (ITP)
Clinical features:

 There may be bruising, particularly purpura in the forearms, petechia

(pinpoint hemorrhages on skin and mucous membranes), nosebleeds
and/or bleeding gums. Petechiae

* Hemorrhages after minor trauma.

* Menorrhagia in the women
* Serious intracerebral or subarachnoid
hemorrhages Occur much less commonly
* Spleen is usually normal in siz and No
lymphadenopathy
Immune thrombocytopenic
purpura (ITP)
Diagnosis
 The diagnosis rests on the clinical features, the presence of
thrombocytopenia, examination of the marrow, and the exclusion of
secondary ITP.

 Tests for antiplatelet antibodies

 The bone marrow usually contains increased numbers of

megakaryocytes, a finding that is common to all forms of
thrombocytopenia that are caused by accelerated platelet destruction.

 A marrow examination can be helpful in excluding marrow failure as a

cause of the thrombocytopenia. splenectomy, which normalizes the
platelet count and induces a complete remission in more than two-thirds
of patients
Immune thrombocytopenic
purpura (ITP
Treatment
1-Steroid : 80% of the patient response on high
dose steroid therapy
2- Splenectomy
3- High dose IV immunoimmunoglobulin
4- Immunosuppressive therapy

Post transfusio thrombocytopenia

 Occurs 10 days post blood transfusion
 It due to antibodies in the recipient developing against antigen (Ag) on
(donor)platelet
Thrombotic thrombocytopenic
purpura
 Is a rare disorder of the blood-coagulation system, causing extensive
microscopic thromboses to form in small blood vessels throughout the body
(thrombotic microangiopathy).

 The term thrombotic microangiopathies include thrombotic thrombocytopenic

purpura (TTP)and hemolytic-uremic syndrome

 (HUS) is a rare disorder of the blood coagulation system, causing multiple blood
clots to form in blood vessels also associated with microangiopathic hemolytic
anemia and thrombocytopenia

 Distinguished from TTP by the

*Absence of neurologic symptoms,
*The dominance of acute renal failure, and
*An onset in childhood .
Thrombotic thrombocytopenic
purpura

 Fundamental to both of these conditions is the widespread formation of

hyaline thrombi in the microcirculation that are composed primarily of
dense aggregates of platelets surrounded by fibrin.

 The consumption of platelets leads to thrombocytopenia, and the

narrowing of blood vessels by the thrombi results in a microangiopathic
hemolytic anemia.
Thrombotic thrombocytopenic
purpura

 The incidence of TTP is about 4-6- per million people per year.

 Most cases of primary TTP arise from inhibition of the enzyme

ADAMTS13, which is responsible for the breakdown of the so-called
von Willebrand factor this leads to
* Hemolysis
* End-organ ischemic damage,
Thrombotic thrombocytopenic
purpura

Signe &symptom

 Fluctuating neurological symptoms, behavior, altered mental status, s

 Stroke or headache) 65%
 Kidney failure (46%

 Fever 33%

 Thrombocytopenia (low platelet count), leading to bruising or purpura

 Microangiopathic hemolytic anemia (anemia ,jaundice and a characteristic

blood film.
 A patient may notice dark urine from the hemolytic anemia.
Thrombotic thrombocytopenic purpura

The combination of the symptoms and a routine blood film

often lead to the detection of
schistocytes (fragmented red cells) and "helmet cells" on the
.blood film

This is indicative of breakdown of red blood cells through

factors in the small blood vessels
Thrombotic thrombocytopenic purpura
Secondary TTP
It comprises about 40% of all cases of TTP.
[:Predisposingfactors are

Cancer -
Bone marrow transplantation -
Pregnancy -
:Medication use -
Quinine
HIV-1 infection
The mechanism of secondary TTP is poorly understood, as
ADAMTS13 activity is generally not as depressed as in
.idiopathic TTP, and inihibitors cannot be detected
Thrombotic thrombocytopenic
purpura

Prognosis
 The mortality rate is approximately 95% for
untreated cases, but the prognosis is reasonably favorable (80-90% for
patients with idiopathic TTP diagnosed and treated early with
plasmapheresis.
 Secondary TTP still has poor prognosis, with mortality rates despite
treatment being reported as 59% to100 %

Treatment
 plasmapheresishas become the treatment of choice for TTP.
 This is an exchange transfusion involving removal of the patient's
blood plasma and replacement with donor plasma (fresh frozen plasma