Salwa Hindawi

Salwa Hindawi

Salwa HindawiMSc, MRCPath, CTM RCPEDirector of Blood Transfusion ServicesKing Abdulaziz University HospitalJeddah, Saudi Arabia

Salwa Hindawi

PLATELETS

Produced from megakaryocytes in the bone marrow

Mean survival: 8-10 daysRemoved from circulation by cells of the

monocyte-macrophage system1/3 of the total platelet mass is found in the

spleen

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Electron Micrscopy of Platelet

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DEFINITION<150,000 platelets/microliter (nml 150,000-

400,000)2.5 % of the nml population have thisIf platelet count >20,000, usually no serious

spontaneous bleedingIf less than <10,000, risk of bleeding

increases and may necessitate transfusion

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MECHANISMS OF THROMBOCYTOPENIADecreased platelet production

Increased platelet destruction

Dilutional/distributional

Pseudothrombocytopenia

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MEDICATIONS

QuinidineQuinineRifampinBactrimMethyldopaAcetaminophenDigoxinDiclofenac

AmphotericinVancomycinAmiodaronePiperacillinSulfasalazineEthambutolLithiumheparin

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MEDICATIONSMethicillinINHMinoxidilNitroglycerine

HaldolTamoxifenDiazepamGold

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ITPAutoimmune etiology (IgG antibody to

platelets)Etiology

30% drug related30% underlying disease (connective tissue

disorders, lymphoma, CLL)30% idiopathic10% viruses (HIV)

Platelets are hyperfunctional (spontaneous bleeding is rare)

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Idiopathic Thrombocytopenic Purpura (ITP)

Autoimmune disease of children and adults Sustained Low platelet countNo other causes )exclusion)

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Pathophysiology

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

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Platelet destruction Low bleeding + by platelet through mucusplatelet acrophages count membranesAuto Ab RES

Pathophysiology

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Clinical Features of ITP in Children and Adults

Feature Children Adults

Occurrence Peak age (yr) 2-4 15-40 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 109/L Most <20 x 109/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

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APPROACH TO DIAGNOSIS

HISTORY AND PHYSICAL EXAMINAIONRecent viral historyDiagnosed hematological diseaseFamily historyRecent live virus vaccination (measles)Poor nutritional statesMedicationsPregnancy

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Diagnosis

Diagnosis by Exclusion

1 – Clinical finding

Bleeding and /or purpura

Isolated thrombocytopeniaNo evidence of other disease

2 – peripheral blood smear3 – platelet antibody test

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4-Auto-immune ProfileAntiphospholipid syndrome

5-B.M.A. in the presence of Atypical clinical features or no response to Rx better before initiation of steroid therapy

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PERIPHERAL BLOOD SMEAR

“GOLD STANDARD”Check for platelet clumping, platelet size,

RBC morphology, presence of immature WBCs

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Deferential DiagnosisSpuriousCongenital ThrombocytopeniaFanconi anaemiaAplastic anaemiaAcute leukemiaAutoimmune diseases (SLE)HypersplenismMicroangiopathy

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Management

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Important Points to consider:

Observation & follow upLet the treatment fit the patient (treat cases

individually)Evidence based medicine through randomized

controlled trials and or clinical practice

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Goal of the treatment Not to achieve a normal platelet count but

to prevent bleeding 2 options:

1. Counseling and observation2. or Rx if: low platelet and/or bleeding

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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 50-75 ug/kg High dose Dexamethasone 40mg/Kg x 4 days for

6 cycles

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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 104/L

SplenectomyIntroduced in 1916Two thirds of patients achieve remissionineffective medical management or/and therapy

associated toxicity

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• Oral prednisone (dose as pre-splenectomy)

• IVIg 0.8-1.0 g/kg; repeat once if platelet

response at 48-72 hours inadequate

• IV anti-D IV (Rh(D)-positive patients only),

50-75g/kg • Other (eg, azathioprine,

cyclophosphamide, vincristine, danazol).

Medical therapy after failed Medical therapy after failed splenectomysplenectomy or refusal to allow splenectomyor refusal to allow splenectomy

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

Emergency therapy

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

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Azathioprine, cyclosporine Vincaalkaloid, cyclophosphamide

Immunosuppressive & Chemotherapy

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Platelet Transfusion

Evaluate the case

Life threatened emergency

IVIG

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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.

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ConclusionsLearn from our mistakesObserve the patients, treat only when it is

really needed.Treat individual cases.Platelet transfusion is contraindicatedEvidence based medicine randomized control

trials for management of ITP.

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References Immune Thrombocytopenic Purpura Let the

treatment fit the patient, George, et alEditorial – New England Journal of Medicine January 13,2004.

Initial Treatment of Immune Thrombocytopenia Purpura with high-dose dexamethasone Cheng, et al, January 13, 2004.

Guidelines for the Investigation & Management of Idiopathic Thrombocytopenic Purpura in adult, children and in pregnancy, British Journal of Haematology 2003.

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Pathogenesis and Management of Chronic Idiopathic Thrombocytopenic Purpura An Update, Renchiyang, Zhong Chao Han; International Journal of Haematology , Aug. 1999.

Blanchette V, Freedman J, Garvey B., Management of Chronic ImmuneThrombocytopenic Purpura in Children and Adults, Semin Haematol, 1998.

Idiopathic Thrombocytopenic Purpura: A Concise Summary of the Pathophysiology and Diagnosis in Children and Adults. James N. George & Gary E. Raskob; Seminars in Haematology 1998.

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.

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