PLATELET DISODERS

DR LALITHA M

Assistant Professor,

Department of Paediatrics

OBJECTIVES

What is hemostasis Sequence of events Platelet normal morphology and counts Thrombocytopenia Immune thrombocytopenic purpura Platelet function disorders Thrombocytosis

HEMOSTASIS

Hemostasis is an active process that clots blood in areas of blood vessel injury and limit the bleeding

Over time, the clot is lysed by the fibrinolytic system, and normal blood flow is restored

The main components of the hemostatic process are :

i. vessel wall

ii. platelets

iii. coagulation proteins

iv. anticoagulant proteins and

v. fibrinolytic system

General sequence of events leading to hemostasis

Arteriolar vasoconstriction

Primary hemostatic plug formation

Secondary hemostatic plug formation

Clot stablisation and resorption

Coagulation cascade

Prothrombotic effects of endothelial cells

Antithrombotic effects of endothelial cells

PLATELET DISORDERS

PLATELETS

Platelets are disc shaped anucleate cell fragments They are shed from megakaryocytes in the bone marrow

into the bloodstream. Their function depends on several glycoprotein receptors

and two types of cytoplasmic granules: Alpha-Granules AND Dense (or ) delta granules

Main regulator of its production is the hormone thrombopoietin (TPO), which is synthesized in the liver.

Normal platelet count = 150,000–400,000/mm3. Circulate with an average life span of 7–10 days.

Disorders of platelets

Disorders in the number of platelets

Functional Disorders (Qualitative)

Thrombocytopenia Thrombocytosis

decreased platelets< 150000/mm3

increased platelets> 400000/mm3

Quantitative Platelet disorders

Diagnostic Tools

Bleeding time(3-12min)

Peripheral blood smears-platelet number & morphology

In vitro platelet function analyzer 100

Platelet aggregation tests

Bone marrow examination

INFECTIONS-Dengue,malaria,scrub typhus

IMMUNE THROMBOCYTOPENIC PURPURA

The most common cause of acute onset of thrombocytopenia(<100 000/mm3) in an otherwise well child

Occurs due to production of autoantibodies against the platelet glycoprotein complexes, αIIb-β3 and GPIb.

After binding of the antibody to the platelet surface, circulating antibody-coated platelets are recognized by the Fc receptor on splenic macrophages and destroyed.

Current definitions

Newly diagnosed ITP : From diagnosis to 3 months

Persistent ITP : 3-12 months after diagnosis

Chronic ITP : >12 months after diagnosis (previously defined as >6 months after diagnosis)

Clinical features

A previously healthy child presents with sudden onset of generalized petechiae and purpura

There may be bleeding from the gums and mucous membranes

Usually there is a history of a preceding viral infection 1-4 wk before the onset of thrombocytopenia

Rare below 2 years of age

Examination

Findings on physical examination are normal, other than the finding of petechiae and purpura

The presence of abnormal findings such as: hepatosplenomegaly, bone or joint pain, remarkable lymphadenopathy ,other cytopenias, or congenital anomalies suggests other diagnoses (leukemia, syndromes)

SEVERITY OF ITP

The severity of bleeding in ITP is based on symptoms and signs, but not platelet count:

1. No symptoms

2. Mild symptoms: bruising and petechiae, occasional minor epistaxis, very little interference with daily living

3. Moderate: more severe skin and mucosal lesions, more

troublesome epistaxis and menorrhagia

4. Severe: bleeding episodes—menorrhagia, epistaxis, malena— requiring transfusion or hospitalization, symptoms interfering seriously with the quality of life

Diagnosis

Complete blood count and blood film examination are usually sufficient

large platelets are seen on a peripheral blood and an adequate or increased number of megakaryocytes in the BM

Indications for bone marrow aspiration/biopsy : - abnormal WBC or differential count

- unexplained anemia as well as findings on history and physical examination suggestive of a bone marrow failure syndrome or malignancy.

Rule out infections especially if child is febrile

Treatment

The majority of children achieve spontaneous remission and do not suffer major bleeding complications

The expectant ‘watch and wait’ policy of management is recommended for such patients

Platelet transfusion in ITP is usually contraindicated unless life-threatening bleeding is present

Only in life threatening bleeds like intracranial hemorrhage transfusion of platelets is recommended

For emergency treatment : intravenous methyl prednisolone or oral prednisolone1 mg/kg PO × 7 d &taper over 3 wk OR

4 mg/kg PO for 4 d or IVIG(1 g/kg IV single dose) anti-D(50-75 ug/kg IV single dose)

Antifibrinolytics such as tranexamic acid 10-15 mg/kg intravenously 6-hourly are useful to control bleeding

Splenectomy is the definitive treatment when refractory to above treatment

In chronic refractory ITP: immunosuppressants (rituximab), thrombopoeitin antagonists (eltrombopag) are used

Acquired Abnormalities of Platelet Function

MYELOPROLIFERATIVE DISEASE

DYSPROTEINEMIA

CARDIOPULMONARY BYPASS

UREMIA

LIVER DISEASE

DRUG INHIBITION

Congenital disorders of platelet function

Von Willebrand Disease

Glanzmann’s Thrombasthenia

Bernard-soulier Syndrome

Bernard-Soulier Syndrome

Occurs due to defect in the genes forming the GPIb complex of glycoproteins Ibα, Ibβ, V, and IX resulting in defective platelet adhesion

This syndrome is characterized by thrombocytopenia, with giant platelets and markedly prolonged bleeding time (>20 min)

Platelet aggregation tests show absent ristocetin-induced platelet aggregation but normal aggregation to all other agonists.

Glanzmann’s Thrombasthenia

caused by deficiency of the platelet fibrinogen receptor αIIb-β3 resulting in defective platelet aggregation

Platelets have normal size

PFA-100 or bleeding time are markedly abnormal

Aggregation studies show abnormal or absent aggregation with all agonists used except Ristocetin

.

Treatment

In all but severe platelet function defects, desmopressin

(0.3 μg/kg IV/nasal) may be used for mild to moderate bleeding

platelet transfusions of 1 unit/5-10 kg may be life saving in severe bleeding

Thrombocytosis

Primary thrombocytosis

Secondary thrombocytosis

Thrombocytosis –secondary causes

1. Iron deficiency;

2. Inflammation, cancer, or infection (reactive thrombocytosis); or

3. An underlying myeloproliferative process [essential thrombocythemia or polycythemia vera or, rarely, myelodysplastic process.

4. Medications that can cause reactive thrombocytosis include: Epinephrine (Adrenalin Chloride, EpiPen) Tretinoin Vincristine

Patients should be evaluated for underlying inflammation or malignancy,

and iron deficiency

Usually does not cause any symptoms

Essential thrombocythaemia (ET) is a condition affecting the cells in the bone marrow leading to overproduction of platelets, leading to an increased propensity to thrombosis formation and blockage of blood vessels

Some people have a change (mutation) in a gene, called the JAK2 gene

Rare in children

Signs and Symptoms of essential thrombocytosis

Heart attack or stroke

Headache

Burning or throbbing pain, redness, and swelling of the hands and feet

Bruising

Gastrointestinal bleeding or blood in the urine

Treatment

Low-dose aspirin -- may treat headache and burning pain in the skin

Hydroxyurea or anagrelide -- reduces number of blood cells.

Aminocaproic acid -- reduces bleeding. This treatment may be used before surgery to prevent bleeding

Thank you

QUESTIONS

Write the sequence of events in hemostasis What is the normal platelet count What is thrombocytopenia Platelets deficiency manifest with: a) superficial bleed

b) deep bleed?? Write four important causes of thrombocytopenia in

children What is the only Indication for platelet transfusion in

ITP Name platelet function disorders