F. Mertzlufft

On the prophylactic and therapeutic use of danaparoid sodium (Orgaran®) in patients with heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a rare but dangerous complication of heparin prophylaxis or treatment. The present laboratory tests to measure heparin-associated antibodies are not specific. The diagnosis of HIT mainly depends on the decrease in platelet count and on clinical symptoms. To evaluate clinical outcome, bleeding complications and platelet counts were evaluated in 45 patients with HIT type II (HIT II) treated prophylactically (subcutaneous injections) or therapeutically (intravenous infusion) with danaparoid. Group I included 24 patients with HIT II without thromboembolic complications who received danaparoid twice daily subcutaneously (10 IU/kg) for a mean of 16 days. Group II included 21 patients with thromboembolic complications. They were treated with intravenous danaparoid (2.6 IU/kg/h ± 1.1) for a mean of 17 days. During subcutaneous prophylaxis, mean anti-Xa levels of 0.2 U/mL and during intravenous treatment, mean anti-Xa levels of 0.4 U/mL were reached. No deaths, amputations, or serious bleeding complications occurred, and no new thromboses were observed in both patient groups.Treatment with danaparoid led to a fast normalization of the platelet counts. This normalization occurred earlier and the concentration of platelets was higher in patients treated with intravenous doses. Danaparoid with subsequent vitamin K-antagonist treatment effectively prevents thromboembolic complications in patients with HIT.

Therapeutische Hypothermie und Säure-Basen-Management

ZusammenfassungDie moderate Hypothermie hat in der letzten Dekade als Therapieoption bei akut neurologischen Krankheitsbildern eine Renaissance erfahren. Bei eindeutigen Therapieerfolgen ist es allerdings ein personal- und kostenintensives Therapieverfahren, das für eine erfolgreiche Anwendung umfangreiche physiologische Kenntnisse und klinische Erfahrung verlangt. Gerade das Erkennen und Beherrschen von Nebeneffekten, die mit fallender Temperatur und steigender Kühldauer zunehmen, entscheiden oftmals über den endgültigen Therapieerfolg.Eine weitere Besonderheit liegt in der Adaptierung von Homöostaseparametern an eine grundlegend pathophysiologische Temperaturkonstellation. Dies gilt insbesondere für die Steuerung des Säure-Basen-Haushalts. Grundsätzlich kommen dabei zwei Therapieregime zur Anwendung, die sich dahingehend unterscheiden, dass unter Hypothermie in einem Fall der pH (pH-stat) oder aber der H+/OH−-Quotient (α-stat) konstant bleibt. Beim Fehlen vergleichender klinischer prospektiver Daten hinsichtlich eines neurologischen Gesamtergebnisses erscheint es unter evidenzbasierten Kriterien schwierig, die beiden Regime einer klinischen Wertung zu unterziehen. Allerdings sprechen sowohl experimentelle Daten als auch pathophysiologische Überlegungen für ein entsprechend differenziertes Vorgehen beim Einsatz der therapeutischen Hypothermie. Eine endgültige Bewertung kann allerdings erst beim Vorliegen prospektiver klinischer Studien vorgenommen werden.AbstractModerate hypothermia is being increasingly advocated for acute neurological clinical situations. In case of proved clinical success, however, it is relatively time consuming and requires personal and structural resources. In addition, profound knowledge and a sound understanding of the physiology of hypothermia are necessary prerequisites. In particular, the variety of untoward effects, which increase with decreasing temperature, underline the need for specific diagnostic and therapeutic skills. A further challenge is associated with the adaptation of the parameters of homoeostasis to a basically altered temperature. Among these, management of acid-base balance is a managerial cornerstone. In principle, two different regimens may be used, i.e. the pH-stat and the α-stat regimes. Applying pH-stat during hypothermia means keeping the pH constant, whereas the H+/OH− quotient is held constant when relying on the α-stat regime. Because of the lack of prospective clinical data any comparative evaluation of the two alternatives actually remains a matter of speculation. However, experimental data as well as physiological considerations may support an illness-oriented differentiated approach (e.g. increased cerebral pressure vs. cardiac arrest vs. stroke). Prospective studies are required to allow an evidence-based and substantiated clinical decision regarding the management of pCO2 and pH during therapeutic hypothermia.