Platelet disoders

Platelet Disorders done by Dr.Lalitha AP,Department of Pediatrics

1. PLATELET DISODERS DR LALITHA M Assistant Professor, Department of Paediatrics

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

3. 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 : vessel wall platelets coagulation proteins anticoagulant proteins and fibrinolytic system

4. General sequence of events leading to hemostasis Arteriolar vasoconstriction Primary hemostatic plug formation Secondary hemostatic plug formation Clot stablisation and resorption

5. Coagulation cascade

6. PLATELET DISORDERS

7. 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.

8. Thrombocytopenia Thrombocytosis decreased platelets < 150000/mm3 increased platelets > 400000/mm3 Quantitative Platelet disorders

9. Diagnostic Tools Bleeding time(3-12min) Peripheral blood smears-platelet number & morphology In vitro platelet function analyzer 100 Platelet aggregation tests Bone marrow examination

10. INFECTIONS- Dengue,malaria,scrub typhus

11. 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.

12. 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)

13. 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

14. E xamination 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 )

15. SEVERITY OF ITP T he 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

16. D iagnosis 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

17. T reatment 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

18. For emergency treatment : intravenous methyl prednisolone or oral prednisolone 1 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

19. Acquired Abnormalities of Platelet Function

20. Congenital disorders of platelet function

21. Bernard- S oulier 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.

22. 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 .

23. 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

24. Thrombocytosis Primary thrombocytosis Secondary thrombocytosis

25. Thrombocytosis –secondary causes Iron deficiency; Inflammation, cancer, or infection (reactive thrombocytosis); or An underlying myeloproliferative process [essential thrombocythemia or polycythemia vera or, rarely, myelodysplastic process. 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

26. 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

27. 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

28. 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

29. Thank you

30. 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