Use of a Low-Molecular-Weight Heparinoid (Danaparoid Sodium) for Continuous Renal Replacement Therapy in Intensive Care Patients

Abstract

The purpose of this study was to evaluate the efficacy and safety of danaparoid in the treatment of critically ill patients with acute renal failure and suspected heparin-induced thrombocytopenia (HIT) needing renal replacement therapy (RRT). We conducted a retrospective analysis of 13 consecutive intensive care patients with acute renal failure and suspected HIT who were treated with danaparoid for at least 3 days during RRT. In eight patients, continuous venovenous hemofiltration was performed. The mean infusion rate of danaparoid was 140 +/- 86 U/hour. Filter exchange was necessary every 37.5 hours. In five patients, continuous venovenous hemodialysis was used. A bolus injection of 750 U danaparoid was followed by a mean infusion rate of 138 +/- 122 U/hour. Filters were exchanged every 24 hours. In 7 of 13 patients, even a low mean infusion rate of 88 +/- 35 U/hour was efficient. Mean anti-Xa (aXa) levels were approximately 0.4 +/- 0.2 aXa U/mL. Persistent thrombocytopenia despite discontinuation of heparin treatment was observed in 9 of 13 patients, owing to disseminated intravascular coagulation (DIC). HIT was confirmed by an increase in platelet count and positive heparin-induced antibodies in 2 of 13 patients. No thromboembolic complications occurred, but major bleeding was observed in 6 of 13 patients, which could be explained by consumption of coagulation factors and platelets due to DIC in 5 of 6 patients. Nine of 13 patients died of multiorgan failure or sepsis, or both. In none of these patients was the fatal outcome related to danaparoid treatment. In critically ill patients with renal impairment and suspected HIT, a bolus injection of 750 U danaparoid followed by a mean infusion rate of 50 to 150 U/hour appears to be a safe and efficient treatment option when alternative anticoagulation is necessary.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia

“…17,68,69 One study reported on 6 patients with HIT with regard to the outcomes of skin necrosis, limb gangrene, amputations, and death; 1 study involved a retrospective medical record review of patients with HIT who experienced venous limb gangrene; and 1 study reported on the outcome of thrombosis in 21 patients with isolated HIT. [68][69][70] The EtD framework is shown online at https://dbep.gradepro.org/profile/2EDAF7FC-665F-302A-97CA-ED3B70A9A133.…”

“…We identified nonrandomized studies evaluating the use of argatroban, danaparoid, fondaparinux, bivalirudin, and rivaroxaban. Ten studies reported on treatment with argatroban, [111][112][113][114][115][116][117][118][119][120] 3 studies reported on treatment with danaparoid, 70,121,122 3 studies reported on treatment with fondaparinux, [123][124][125] 2 studies reported on treatment with bivalirudin, 57,126 and 1 study reported on treatment with rivaroxaban. 127 These studies reported on the outcomes of bleeding, thromboembolic events, mortality, and serious adverse events.…”

Regional Citrate Anticoagulation in Continuous Hemodialysis – Acid-Base and Electrolyte Balance at an Increased Dose of Dialysis

“…Heparin is the most frequently used anticoagulant but is associated with several disadvantages such as severe hemorrhagic complications [1, 2]. A variety of different anticoagulation protocols including the use of direct thrombin inhibitors [3], prostacyclin [4], low-molecular-weight heparins [5] or danaparoid [6] have not proven to be valid alternatives as they all are associated with important side effects including hemorrhages and/or vasodepression. A complete anticoagulation-free dialysis using saline flushes to prevent filter clotting has been suggested by different authors [7].…”

Heparin‐induced thrombocytopenia during renal replacement therapy

“…For continuous renal replacement therapy (CRRT) an initial bolus dose is required, and if there is no hemorrhagic risk then administer 2500 U (35 U/kg) of danaparoid followed by an initial infusion of 400 U/hr and then adjusted (usually between 200 and 400 U/hr) to the desired anti‐Xa (0.4–0.6) 36 . Although others have reported that lower doses of danaparoid, initial bolus of 750 U followed by a mean infusion of 138 U/hr, have been effective maintaining an anti‐Xa activity of 0.2 to 0.6 38 …”

“…36 Although others have reported that lower doses of danaparoid, initial bolus of 750 U followed by a mean infusion of 138 U/hr, have been effective maintaining an anti-Xa activity of 0.2 to 0.6. 38 The major problem with danaparoid is the prolonged half-life. If bleeding occurs, there is no simple antidote, and patients may require supportive treatment with activated factor VII concentrate or fresh frozen plasma.…”