HEPARIN INDUCED THROMBOCYTOPENIA

1. HEPARIN INDUCED THROMBOCYTOPENIA GALILA ZAHER MBB ch, dip C Path, MRC Path

2. Heparin induced thrombocytopenia(HIT) • HIT: is an immune mediated side effect which can be life threatening . • Incidence : 1-3%of patient receiving heparin.

3. Heparin induced thrombocytopenia • Higher risk for HIT *Therapeutic > prophylactic doses . *Bovine lung extract > porcine heparin *Unfractunated heparin > LMWH. • HIT *IV , SC, hepsal flush , extra corporal blood circuit & heparin coated materials.

4. Pathogenesis • Heparin treatment release platelet factor 4 . • Heparin can bind to PF4 on platelet surface & vascular endothelium. • Antibodies are directed against heparin-PF4 (H-PF4). • Antibodies involved in HIT are usually IgG , but IgA & IgM have been reported.

5. Type 1 HIT • The most common form of HIT. • Early onset (3-5d). • Mild thrombocytopenia(80-100x109/l). • Direct effect of heparin . • Reversible • Asymptomatic .

6. Type II HIT • Less frequent than type I HIT • Delayed onset (5-14d). • Plt count is <60x109/L • Can be life threatening 29% mortality rate (HITT) . • Immunological reaction . • Requires clinical intervention & immediate discontinuation of heparin.

7. Ice burg model: Multiple thrombosis 0.01-0.1% Isolated thrombosis 30-80% Symptomatic thrombocytopenia 30-50-% HIT-IgG seroconversion 0-10% HIT-IgG

8. Clinical presentation of type II HIT • Males and females are equally affected. • All ages. • Venous thrombosis more common than arterial . • Patient who develop skin lesions at heparin injection sites are at increased risk of thrombosis. • CVDarterial . • Post operativevenous thrombosis .

9. Clinical presentation *Venous thrombosis : DVT&PE. Warfarin induced venous limb gangrene. Cerebral sinus thrombosis . Adrenal hemorrhagic infarction . *Arterial thrombosis: lower limb (distal aortic or iliofemoral). Stroke & Myocardial infarction. *Acute plt activation syndrome : *Skin lesions

10. Laboratory diagnosis of HIT Existing lab methods do not distinguish between HIT & HITTS. * 14C Seratonin release assay . * H-PF4 ELISA . * The platelets aggregation assay. * Flow-cytometric assay. Until improved laboratory diagnosis of HIT clinical impression are best used to direct therapy in patient with suspected HIT

11. Flow cytometry in diagnosis of HIT • Provides rapid diagnosis . • 100% specificity and sensitivity . • Reproducible . • flow cytometric assay of CD62P can distinguish HIT from HITTS.

12. Heparin therapy • Regular platelets count . • Type I HIT syndrome -observation . • Type II HIT syndrome : *D/C heparin *no platelet concentrate *no warfarin during the acute phase *no LMWH *Heparinoid

13. Thrombin inhibitors HIRUIDIN: *Natural hiruidin : The leech salivary extract (hirudo medicinalis). *synthetic hirudin (argatroban). *recombinant (r- hiruidin) . Danaparoid. Hirulogs.

14. PLASMAPHERESIS • Removal of plasma &replacement with normal plasma or colloids. • It has been done on 3 consecutive days. • Early treatment (4 days) reduces the incidence of mortality • It dose not affect the number of the thrombotic events .

15. Extremity Arterial Thrombosis & Stroke . • Digits only : *Argatroban . • Entire extremity : *Thrombolytic therapy, *Continue argatroban, *Plasmapharesis. • Stroke with no evidence of hemorrhage: *Argatroban • Stroke with evidence of hemorrhage : *Plasmapheresis.

16. Laboratory diagnosis .ctd • Combined results of the three assays enhances the positive response to 83%of the total population with HIT. • The combination of the three testing with multiple samples offers the best chance of confirming a positive diagnosis of HIT . • Clinical event & a positive reliable laboratory test confirms the diagnosis of HIT.

17. 14C serotonin release assay • The gold standard for diagnosis. • It is a biologic assay. • It requires the use of radioactive materials. • It has a sensitivity of 55%. • The complexity & the slow turn around time of the assay compromise its practical usefulness for immediate treatment decisions.

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