Salwa Hindawi

MSc, MRCPath, CTM RCPE Director of Blood Transfusion Services King Abdulaziz University Hospital Jeddah, Saudi Arabia

Salwa Hindawi PLATELETS Produced from megakaryocytes in the bone marrow Mean survival: 8-10 days Removed from circulation by cells of the monocyte- macrophage system 1/3 of the total platelet mass is found in the spleen

Salwa Hindawi Electron Micrscopy of Platelet

Salwa Hindawi DEFINITION <150,000 platelets/microliter (nml 150, ,000) 2.5 % of the nml population have this If platelet count >20,000, usually no serious spontaneous bleeding If less than <10,000, risk of bleeding increases and may necessitate transfusion

Salwa Hindawi MECHANISMS OF THROMBOCYTOPENIA Decreased platelet production Increased platelet destruction Dilutional/distributional Pseudothrombocytopenia

Salwa Hindawi MEDICATIONS Quinidine Quinine Rifampin Bactrim Methyldopa Acetaminophen Digoxin Diclofenac Amphotericin Vancomycin Amiodarone Piperacillin Sulfasalazine Ethambutol Lithium heparin

Salwa Hindawi MEDICATIONS Methicillin INH Minoxidil Nitroglycerine Haldol Tamoxifen Diazepam Gold

Salwa Hindawi ITP Autoimmune etiology (IgG antibody to platelets) Etiology 30% drug related 30% underlying disease (connective tissue disorders, lymphoma, CLL) 30% idiopathic 10% viruses (HIV) Platelets are hyperfunctional (spontaneous bleeding is rare)

Salwa Hindawi Idiopathic Thrombocytopenic Purpura (ITP) Autoimmune disease of children and adults Sustained Low platelet count No other causes )exclusion)

Salwa Hindawi Pathophysiology Immune Mediated Mechanism  increase HLA-DR expression defects in cellular and humoral immunity  specific autoantibody production to GpIIb/IIIa and Gp16-IX Antigens

Salwa Hindawi Platelet  destruction  Low  bleeding + by platelet through mucus platelet acrophages count membranes Auto Ab RES Pathophysiology

Salwa Hindawi Clinical Features of ITP in Children and Adults Feature Children Adults Occurrence Peak age (yr) Sex (F:M) Equal 2:6:1 Presentation Onset Acute (most with symptoms < 1 week) Insidious (most with symptoms <2 months) Symptoms Purpura (<10% with severe bleeding) Purpura (typically bleeding not severe) Platelet count Most <20 x 10 9 /L Most <20 x 10 9 /L Course Spontaneous remission 83% 2% Chronic disease 24%43% Response to splenectomy 71%66% Eventual complete recovery 89%64% Morbidity and mortality Cerebral hemorrhage <1%3% Hemorrhagic death <1%4% Mortality of chronic refractory 2%5% disease

Salwa Hindawi APPROACH TO DIAGNOSIS HISTORY AND PHYSICAL EXAMINAION Recent viral history Diagnosed hematological disease Family history Recent live virus vaccination (measles) Poor nutritional states Medications Pregnancy

Salwa Hindawi Diagnosis Diagnosis by Exclusion 1 – Clinical finding Bleeding and /or purpura Isolated thrombocytopenia No evidence of other disease 2 – peripheral blood smear 3 – platelet antibody test

Salwa Hindawi 4-Auto-immune Profile Antiphospholipid syndrome 5-B.M.A. in the presence of Atypical clinical features or no response to Rx better before initiation of steroid therapy

Salwa Hindawi PERIPHERAL BLOOD SMEAR “GOLD STANDARD” Check for platelet clumping, platelet size, RBC morphology, presence of immature WBCs

Salwa Hindawi Deferential Diagnosis Spurious Congenital Thrombocytopenia Fanconi anaemia Aplastic anaemia Acute leukemia Autoimmune diseases (SLE) Hypersplenism Microangiopathy

Salwa Hindawi Management

Salwa Hindawi Important Points to consider: Observation & follow up Let the treatment fit the patient (treat cases individually) Evidence based medicine through randomized controlled trials and or clinical practice

Salwa Hindawi Goal of the treatment Not to achieve a normal platelet count but to prevent bleeding 2 options: 1. Counseling and observation 2. or Rx if: low platelet and/or bleeding

Salwa Hindawi Management of ITP Prednisone1-2 mg/kg daily 60-80% achieve remission Intravenous immunoglobulin 0.4 g/kg daily x 5 days, or 1 g/kg/d x 2 days I.V. Anti-D ug/kg High dose Dexamethasone 40mg/Kg x 4 days for 6 cycles

Salwa Hindawi High dose methyle prednisolone (HDMP) Oral 7 days course (30 mg/kg/d/3 days then 20 mg/kg/d x 4 days) x 6 courses  platelet count by day 7 > 50 x 10 4 /L Splenectomy Introduced in 1916 Two thirds of patients achieve remission ineffective medical management or/and therapy associated toxicity

Salwa Hindawi Oral prednisone (dose as pre- splenectomy) IVIg g/kg; repeat once if platelet response at hours inadequate IV anti-D IV (Rh(D)-positive patients only),  g/kg Other (eg, azathioprine, cyclophosphamide, vincristine, danazol). Medical therapy after failed splenectomy or refusal to allow splenectomy or refusal to allow splenectomy

Salwa Hindawi IV methylprednisolone 30 mg/kg/d (maximum, 1g) for 3 consecutive days IVIg (1-2 g/kg over 2 days) Platelet trasfusion Emergency therapy

Salwa Hindawi Rarely used therapies Interferon-  Cyclosporine A Combination chemotherapy Plasma exchange Staphylococcal protein A immunoadsorption Dapsone Ascorbic acid Colchicine Mabthera Danazol

Salwa Hindawi Azathioprine, cyclosporine Vincaalkaloid, cyclophosphamide Immunosuppressive & Chemotherapy

Salwa Hindawi Platelet Transfusion Evaluate the case Life threatened emergency IVIG

Salwa Hindawi Follow-up Clinical severity in addition to platelet count, CBC should be repeated within 7-10 days of diagnosis and only when there is a clinical indication or signs of resolution of clinical symptoms.

Salwa Hindawi Conclusions Learn from our mistakes Observe the patients, treat only when it is really needed. Treat individual cases. Platelet transfusion is contraindicated Evidence based medicine randomized control trials for management of ITP.

Salwa Hindawi References Immune Thrombocytopenic Purpura Let the treatment fit the patient, George, et al Editorial – New England Journal of Medicine January 13,2004. Initial Treatment of Immune Thrombocytopenia Purpura with high-dose dexamethasone Cheng, et al, January 13, Guidelines for the Investigation & Management of Idiopathic Thrombocytopenic Purpura in adult, children and in pregnancy, British Journal of Haematology 2003.

Salwa Hindawi  Pathogenesis and Management of Chronic Idiopathic Thrombocytopenic Purpura An Update, Renchiyang, Zhong Chao Han; International Journal of Haematology, Aug  Blanchette V, Freedman J, Garvey B., Management of Chronic ImmuneThrombocytopenic Purpura in Children and Adults, Semin Haematol,  Idiopathic Thrombocytopenic Purpura: A Concise Summary of the Pathophysiology and Diagnosis in Children and Adults. James N. George & Gary E. Raskob; Seminars in Haematology  George JN, Woolf SH, Raskob GE, et al: Idiopathic Thrombocytopenic Purpura. A Practice Guideline Developed by Explicit Methods For American Society of Haematology Blood;88:3-40,1996.

Salwa Hindawi