Heparin-induced thrombocytopenia 69.52

Heparin-induced thrombocytopenia type I (non-immunological): Reduction of the platelet count in the early phase of treatment. The drop in platelet count is significantly less than 50%, but without progression despite continuation of treatment with heparin.

Heparin-induced thrombocytopenia type II (immunological).

Occurs in about 1-5% of cases during treatment with unfractionated heparin. In treatment with low-molecular-weight heparin, occurrence in < 1% of cases.

In HIT II, a heparin-induced antibody binds to the IgG-Fc receptor of the thrombocytes and leads to the activation of thrombocytes. Consecutively, procoagulatory microparticles are generated. In addition, platelet proteins (platelet factor 4) are released, which neutralize free heparin. These platelet proteins bind to heparan sulphate, which is present in the endothelial cell membrane. The complex attaches the autoantibodies and activates the endothelial cells, which increases thrombin formation and ultimately results in thrombocytopenia. There is a risk of limb loss due to thrombotic events. There is also a potential danger to the patient's life!

The occurrence of HIT II depends on the duration and dose of heparin treatment as well as the size of the active substance molecule. Longer-chain, unfractionated heparin has a two to three times higher risk of HIT II than low-molecular-weight heparin.

Initially succulent, red-blue to blue-black, painful spots that can develop into large plaques. Formation of hemorrhagic blisters possible.

In about 40% of cases, arterial or venous vascular occlusion occurs (also known as white clot syndrome ).

Note: the presence of HIT can be assessed using the 4T score: thrombocytopenia, timung, thrombosis and other causes of thrombocytopenia, each with a score of 0-2 points. With a value <4, the score has a high negative predictive value.

Detection of antibodies against the platelet factor 4-heparin complex(PF4/heparin complex antibodies) using ELISA.

Performance of a HIPA test.

A functional confirmation test is the heparin-induced platelet aggregation (HIPA) test, which is highly recommended for HIT type II.

Regular laboratory checks.

• Heparin-induced thrombocytopenia type I: self-limiting course with continuation of heparin therapy; spontaneous regression of thrombocytopenia within a few days
• Heparin-induced thrombocytopenia type II: immediate discontinuation of heparin; alternatively, if there is an indication for anticoagulation, treatment should be continued with either the heparinoid danaparoid sodium (Orgaran) or the recombinant hirudin preparation lepirudin (refludan; 0.4 mg/kg bw as a bolus, then continuous infusion 0.15 mg/kg bw).
• If necessary, argatroban (synthetically produced direct thrombin inhibitor) initially 0.5-2 µg/kg bw/min. i.v.; regular laboratory checks!

Remember! Any platelet drop to less than 50% of the initial value or to absolute values < 100,000 platelets/µl must always be considered as heparin-induced thrombocytopenia type II until proven otherwise!

1. Greinacher A et al (2003) Heparin-induced thrombocytopenia. Dtsch Ärztebl 100: 2220-2229
2. Greinacher A et al (1991) A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb haemost 66: 734-736
3. Helbig D et al (2007) Skin and mucosal ulcerations in heparin-induced thrombocytopenia (HIT II). Dermatologist 58: 774-778
4. Warkentin TE et al (2006) Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 108: 2937-2941