Intensivmedizin und Notfallmedizin

, Volume 43, Issue 1, pp 12–28 | Cite as

Die akute heparininduzierte Thrombozytopenie Typ II während der Schwangerschaft

Eine interdisziplinäre Herausforderung
  • H. Schinzel
  • D. Peetz
  • J. Wiechelt
  • M. A. von Mach
  • D. Macciella
ÜBERSICHT

Zusammenfassung

Bei der heparininduzierten Thrombozytopenie Typ II (HIT II) handelt es sich um eine antikörpervermittelte unerwünschte Heparinnebenwirkung. Sie ist charakterisiert durch einen Abfall der Thrombozyten bei gleichzeitig stark erhöhtem Risiko für arterielle und v. a. venöse Thromboembolien. Abhängig von der Größe und Lokalisation der Thromboembolie, den Grund- und Begleiterkrankungen kann rasch eine vital bedrohliche Situation entstehen. In der Schwangerschaft und im Wochenbett stellt die HIT Typ II ein seltenes Ereignis dar, da Heparin in der Gravidität nur bei akuten Thromboembolien bzw. bei Patientinnen mit deutlich erhöhtem Thromboembolierisiko appliziert wird. Auch durch die in den letzten Jahren zunehmende Verwendung von niedermolekularen Heparinen (NMH), anstelle unfraktionierter Heparine (UFH), ist die HIT-II-Inzidenz insgesamt rückläufig. Das Auftreten einer heparininduzierten Thrombozytopenie Typ II stellt in der Schwangerschaft eine interdiziplinäre Herausforderung dar. In der Gravidität und im Puerperium besteht physiologischerweise schon ein hyperkoagulabiler Zustand, der durch die mit der HIT-II-assoziierten vermehrten Thrombingenerierung die Entstehung von Thromboembolien zusätzlich begünstigt. Bereits bei Verdacht HIT Typ II muss das Heparin sofort abgesetzt und unverzüglich eine alternative Antikoagulation eingeleitet werden. Die Diagnosestellung der HIT Typ II ist in der Gravidität erschwert. So kann durch andere Ursachen ein Thrombozytenabfall induziert werden, wie beispielsweise durch ein sich entwickelndes HELLP-Syndrom, durch einen schwangerschaftsassozierten Progress einer idiopathischen thrombozytopenischen Purpura oder auch durch einen medikamententoxischen Effekt. Ferner ist die Objektivierung bei klinischem Thromboembolieverdacht durch die eingeschränkten diagnostischen Möglichkeiten in der Schwangerschaft begrenzt. Der Nachweis von HIT-Antikörpern alleine sichert nicht die Diagnose einer HIT II. In ca. 20% der Fälle unter Therapie mit unfraktionierten Heparinen lassen sich positive HIT-Antkörper nachweisen ohne dass sich eine manifeste HIT Typ II entwickelt. Ein weiteres Problem bei diesem Kollektiv stellen die begrenzten Möglichkeiten und Erfahrungen mit der alternativen Antikoagulation während der Gravidität dar. Die Erfahrungen bezüglich des unmittelbar peripartalen Antikoagulations- und Geburtsmanagements sind rudimentär.

Die Gabe von Vitamin-K-Antagonisten (Kumarinderivate) ist v. a. in der Phase der Organogenese wegen der Gefahr von Fetopathien und in der 2. Hälfte des dritten Trimenons wegen des erhöhten maternalen und kindlichen intra- und peripartalen Blutungsrisikos nicht unproblematisch und nur unter strengsten Kautelen vertretbar. Auch sind Vitamin-K-Antagonisten nicht zur Akuttherapie geeignet, da ihr Wirkungseintritt zu langsam und damit in der Initialphase der akuten HIT II keine ausreichende Antikoagulation zu erzielen ist, wodurch das Risiko von Thromboembolien bzw. deren Progress erhöht wird. Das Heparinoid Danaparoid-Natrium und das rekombinante Hirudin (Lepirudin) stellen eine Alternativen dar, wobei wegen der besseren Datenlage und der intravenösen und insbesondere auch der subkutanen Applikationsform dem Danaparoid der Vorzug bei der Therapie HIT II in der Gravidität zu geben ist. Beide Substanzen sind zwar für die akute Therapie der HIT II zugelassen, jedoch besteht für keines der Präparate eine Zulassung zur HIT-II-Behandlung in der Schwangerschaft. Nach der Entbindung stellen die Vitamin-K-Antagonisten Warfarin oder Phenprocoumon die Therapie der Wahl dar. Die Umstellung sollte hierbei überlappend erfolgen bis ein INR-Wert größer 2,0 erreicht ist. Stillen ist unter Vitamin K-Antagonisten möglich. Berichtet wird über eine Patientin mit akuter Sinusvenenthrombose in der Frühschwangerschaft und der Entwicklung einer HIT Typ II unter der darauf erfolgenden Heparintherapie. Das Management der Langzeit- und peripartalen Antikoagulation mit Danaparoid-Natrium wird dargestellt.

Schlüsselwörter

Schwangerschaft heparininduzierte Thrombozytopenie Typ II alternative Antikoagulation Danaparoid-Langzeitantikoagulation 

Acute heparin-induced thrombocytopenia type II during pregnancy—an interdisciplinary challenge

Summary

Heparin-induced thrombocytopenia type II (HIT type II) is an antibody mediated severe adverse event to heparin. It is characterized simultaneous by a decrease of the platelet count with a strongly increased risk for arterial and venous thromboembolic complications. Depending on the size and localization of the thromboembolism, a rapidly vitally threatening situation can develop. In pregnancy and in puerperium, heparin is applied only with acute thromboembolic events and/or with female patients with clearly increased risk on venous thromboembolism. Since treatment has been changed from unfractionated heparin (UFH) to low-molecular weight heparin (LMWH), the incidence of HIT type II is rare in this collective. The acute HIT II in pregnancy represents an interdisciplinary challenge. In gravidity and in puerperium, a physiologically hypercoagulability already exists. If this is associated with HIT type II, the risk of thromboembolism additionally increases. Upon suspicion HIT type II, heparin administration must be stopped immediately and an alternative anticoagulation has to be introduced. HIT type II in pregnancy is difficult to diagnose. There are a number of other causes, which can induce a decrease in platelets, e. g., a developing HELLP syndrome, the progress of an idiopathic thrombocytopenia or a drug-induced thrombocytopenia. The diagnostic methods for the evaluation of thromboembolism are reduced during pregnancy. In approx. 20% of the cases under therapy with UFH, positive HIT-antibodies can be proven without developing a manifest HIT type II. Therefore, HIT antibodies alone do not prove the diagnosis for HIT type II. Experience with alternative anticoagulation regimes in HIT type II during pregnancy and puerperium is limited. The peripartal experience is rudimentary. Oral anticoagulation with coumarin (vitamin K antagonists) is contraindicated in the initial therapy of HIT type II. Since it takes time until coumarine works, no sufficient anticoagulation can be attained in the acute phase of HIT type II. In addition, the treatment with these substances is dangerous especially in the phase of organogenesis, because it can cause malformation and because of the elevated maternal and the childlike intra- and peripartal bleeding risk in the second half of the third trimester. Danaparoid sodium and recombinant hirudin represent treatment options, whereby because of the better data situation and the intravenous and especially the subcutaneous application form, the application of danaparoid in the therapy of HIT type II is favored in pregnancy. However, neither is specially certified for the HIT II therapy in pregnancy. In puerperium, warfarin or phenprocoumon represent the therapy of the choice, whereby breast-feeding remains possible. We give an overview of the literature and a report on a female patient with an acute thrombosis of the cerebral sinus venous during early pregnancy who developed HIT type II with deep venous thrombosis and pulmonary embolism under heparin treatment. The long-term anticoagulation with danaparoid sodium and peripartale management is presented.

Key words

Pregnancy heparin-induced thrombocytopenia type II alternative anticoagulation danaparoid sodium 

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Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • H. Schinzel
    • 1
  • D. Peetz
    • 2
  • J. Wiechelt
    • 1
  • M. A. von Mach
    • 1
  • D. Macciella
    • 3
  1. 1.II. Medizinische Klinik und PoliklinikJohannes-Gutenberg-Universitätsklinikum MainzMainzGermany
  2. 2.Institut für Klinische Chemie und LaboratoriumsmedizinJohannes-Gutenberg-UniversitätMainz
  3. 3.Klinik für Frauenheilkunde und GeburtshilfeJohannes-Gutenberg-UniversitätsklinikumMainz

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