heparin induced thrombocytopenia

Heparin-Induced Thrombocytopenia

A disease of 100 days

Define

1. A decrease in the platelet count of more than 50% from the highest platelet count value after the start of heparin

2. An onset 5 to 10 days after the start of heparin

3. Hypercoagulability

4. Presence of heparin-dependent, platelet-activating IgG antibodies(PF4 antibody)

• A strongly positive test for Antibody against PF-4 (optical density, >1.5) or positive platelet-activation assay would strongly support the diagnosis of HIT

This definition may change for Type I/II/III/IV HIT

Science

HIT simulates to a bacterial host defence mechanism. PF4 is released from platelet αgranules binds to polyanions such as heparin or polyanions on the surface of bacteria and undergoes a conformational change(super antigen). This immunogenic super antigen stimulate production of IgG. These antibodies bind to PF4–heparin complexes, forming immune complexes. The Fc parts of the IgG bind to platelet Fcγ RIIa receptors, resulting in Fcγ receptor clustering and consequent strong platelet activation and aggregation. This intravascular platelet consumption causes a decrease in the platelet count and the production of platelet derived micro particles that accelerate thrombin generation. HIT antibodies activate monocytes and endothelial cells, inducing additional tissue factor expression. The resulting increase in thrombin generation leads to an increased risk of thrombosis among patients with HIT, providing a rationale for treatment that reduces thrombin generation.

Anti PF4 antibody

• Routine screening for PF4–heparin antibodies is strongly discouraged, patients at intermediate or high risk should undergo this testing. A positive anti–PF4–heparin IgG enzyme immunoassay is necessary for the diagnosis of HIT but is nonspecific. A strongly positive test (optical density, >1.5) or positive platelet-activation assay would strongly support the diagnosis of HIT. Antibodies disappears by 50 to 85 days. Regeneration of antibodies requires at least 5 days (no earlier anamnestic response).Sometimes ,a single bolus within 100 days of previous exposure causes anaphylactic HIT. Heparin within the previous 90 days (especially, ≤30 days), there may be persistent circulating anti–platelet factor 4 (PF4)–heparin antibodies, and HIT can start abruptly on reexposure to heparin (rapid-onset HIT); in this case, HIT is sometimes complicated by an

The drop

4T SCORING

4T score ≥4

Indicates higher pretest probability of HIT and mandates PF4-Heparin IgG antibody quantification .A value ≥2 by optical density raises sensitivity and specificity to higher level.

Difference between HIT & other platelet consumption states

HIT • paradoxical prothrombotic state

• 1 in 5000 hospitalized patients

• 7 to 10 days after Heparin are at the highest risk

• 50% of HIT –thrombotic :DVT/PTE/MI/cerebral sinus thromosis

Others • Marked by bleeding

Thrombosis VS. Bleeding

Variants of typical

• Typical :Between 5 and 10 days after heparin is started, both in 1ST time and reexposure users

• Variants • Sometimes 5 to 10 days after surgery in patients who have been

undergoing haemodialysis for a long time

• Anaphylactic reaction: within 30 minutes after a heparin bolus.

• Delayed onset :Thrombosis up to 3 weeks after the start of heparin

• A disease of 100 days :Even a single 2nd bolus within 1st 100 days after 1st exposure

Guidelines

• ACCP/European guidelines• Low-grade evidence

• Use scoring system

• Probability of HIT before PF4 antibody testing

• Alternative anticoagulation

• ACCP:Patients at high risk (>1%) for HIT ,monitor platelet count every 2 to 3 days between day 4 and day 14

Conclusion

• Suspect HIT when a decrease in the TPC > 50% and thrombosis after 5 to 10 days of heparin

• Then use 4T score for pretest probability of HIT.

• PF4–heparin antibody tests if clinical features reasonably suggest HIT.

• STOP heparin

• START argatroban, danaparoid, fondaparinux, or bivalirudin

• Warfarin should be avoided in patients with acute HIT.

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