Heparin-induced thrombocytopenia

Heparin -induced thrombocytopenia (HIT ) is a disease in which drops by the administration of heparin, an agent for inhibiting blood coagulation, platelet count ( platelets). There are two types of HIT.

Heparin -induced thrombocytopenia type I

HIT type 1 manifests itself in the first days of heparin treatment. It presents itself in a moderate decrease in the number of platelets, which regresses spontaneously after a few days. This error is due to this phenomenon, a direct activation of platelets by the drug. No treatment is necessary. In general, the platelets are not covered by 80.000/μl.

Heparin -induced thrombocytopenia type II

HIT type II is based on antibody formation against heparin / protein complexes. Due to its negative charge of the drug binds to numerous proteins. As the most important disease- triggering factor of the complex of heparin and platelet factor 4 is considered. Platelet Factor 4 is a highly positively charged protein, which is released from blood platelets. Against the drug / protein complex - the antigen - antibody develop some patients. After binding to the complex, the antibodies bind with their Fc portion to a receptor on the platelets. Thereby, the platelets clump to each other and are activated. From this result thrombosis in the venous and arterial system. Extremely rare can also be an inactivation of coagulation with bleeding tendency. First antibodies are measurable six to twenty days after the start of heparin administration.

The incidence of HIT type II depends on the duration of heparin treatment, under-five days, it occurs less frequently. Similarly, a high dose promotes the risk of this complication. Furthermore, the molecular size of the active ingredient by a factor of greater chain length dar. In more platelet factor may be bound per molecule of heparin, which in turn enhances the immunogenicity of the complex. For longer chain, unfractionated heparin has an up to thirty -fold increased risk of HIT type 2 as a low molecular weight heparin. The origin of heparin may refer to the emergence of a HIT influence. Thus, the antibody formation in the extraction of heparin from porcine occurs more frequently than active agent from cattle. Similarly, studies indicate an increased risk in patients female. In the therapy with unfractionated heparin for the occurrence of a HIT type 2 is between 0.5 and 5% from an administration period of five days.

Diagnosis

At first contact with heparin occurs after the latency period in the course of one to two days to a rapid drop of the platelet count to less than half the initial value. Had the patient been previously recognized contact with heparin and antibodies, this may go without latency and with even faster progress on. The diagnosis is divided using a product developed by Greinacher scores clinically probable or improbable. Here, the extent of platelet drop, the duration between the start of heparin administration and the beginning of the platelet drop, the extent of complications, as well as other causes of platelet drop to 0, 1 or 2 points will be provided. The confirmation of the diagnosis with laboratory testing is not possible in principle, but there are, inter alia, ELISA assay with which the antibodies can be detected in about 90-95 % of cases. However, the cases antibodies are also detected in 5-50% depending on the test without ever were to occur a HIT. A new method is the lateral flow immunoassay with the similar ELISA antibodies are found in apparently fewer false-positive results .. The reference method shall be the serotonin release assay. This donor platelets are incubated with radiolabeled C14 - serotonin, which they absorb. Thereafter, the mixture with patient serum and heparin is mixed. The measured radioactivity of the release of serotonin acts as an indicator for the presence of antibodies HIT. In Germany, the heparin -induced platelet activation assay ( HIPA ) has next to naturalized. In this test, just as donor platelets are incubated with patient serum and heparin. As a measure of platelet activation, the turbidity of the sample mixture shall in comparison to a reference sample. In some cases seen during the injection of heparin under the skin a bleeding skin necrosis at the injection site. Comparatively well secured is the HIT, if rise 12-48 hours after discontinuation of heparin and start with an alternative anticoagulant platelet counts again significantly.

Therapy

Heparin should be discontinued already at the first suspicion of HIT type II immediately to the potentially life-threatening complications ( venous and arterial thrombosis can lead to pulmonary embolism and infarction ) should be avoided. To ensure the treatment of the underlying disease progresses, but mainly to prevent the fatal circulatory disorders associated with HIT, must be converted to a different anticoagulant also immediately. The hepatic eliminated argatroban here represents the method of choice is, and has no relevant side effects in addition to the naturally increased bleeding tendency. Alternatives are hirudin ( lepirudin - is in the EU since April 2012 no longer sold by the manufacturer ), for which, however, a " Red Hand " warning is because of rare but fatal anaphylactic reactions, and the heparinoid danaparoid, which has a similar structure as heparin has. Therefore, the latter would have to be released before it is used only if the antibodies responsible for the HIT cross-react with danaparoid (<10 %). Likewise, if the Danaparoidbehandlung on the determination of a coagulation factor, which inhibits the drug to be controlled. The advantage of the danaparoid, however, is that it may be injected subcutaneously (under the skin ), while argatroban and lepirudin continuously intravenously must be provided (via an indwelling ). Treatment with argatroban and hirudin, which directly inhibit necessary for clotting thrombin can be monitored less burdensome on the routine aPTT value. Oral anticoagulants such as phenprocoumon, warfarin and acenocoumarol, which inhibit vitamin K as needed for blood clotting vitamin, are not applicable to a HIT type II in the first two weeks, as may occur as a side effect necrotic disorders. However, following oral anticoagulation is possible and usually also useful. The administration of antiplatelet agents such as aspirin has been shown at the stage of thrombogenesis no significant efficacy. The selective anti - Xa inhibitor fondaparinux, a pentasaccharide, should not be used. Under the administration of fondaparinux it may very well come to a heparin-induced thrombocytopenia, as it also binds to platelet factor 4, albeit weaker than heparin. Fondaparinux is therefore on the one hand even elicit an immune response and on the other hand raise awareness for a very quickly and massively running HIT under heparins.

Forecast

The mortality in HIT type II in connection with the occurrence of thrombotic complications is about 30 %.