Danaparoid-Consensus Recommendations on Its Clinical Use.

(1) Background: Danaparoid sodium is a heparinoid antithrombotic that has been used for over 40 years for prophylaxis of DVT in non-HIT patients and for the treatment of heparin-induced thrombocytopenia (HIT) with and without thrombosis. This update summarises current information on its pharmacology and reviews danaparoid dose management in a broad spectrum of clinical situations, including off-label indications. (2) Methods: Evidence from published clinical studies, case reports, compassionate use of danaparoid, and spontaneously reported serious adverse events is summarised and analysed by an interdisciplinary expert group to develop a consensus on dosing regimens of danaparoid for complex clinical situations, including vulnerable patient populations.

Experience of danaparoid to treat vaccine-induced immune thrombocytopenia and thrombosis, VITT.

Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and may cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management.

Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection.

The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19.

An analysis of clinical outcomes of 91 pregnancies in 83 women treated with danaparoid (Orgaran).

Unlabelled: Danaparoid case reports of 91 pregnancies in 83 patients with a history of thrombophilia and/or intra-uterine growth retardation have been analysed. All had intolerance to the heparins including HIT and acute or past thromboses or a history of repeated pregnancy loss (RPL). Danaparoid was started in the first, second and third trimesters in 60.

[Danaparoid in pregnancy in cases of heparin intolerance - use in 59 cases].

Unlabelled: During the use of fractionated or unfractionated heparin adverse events frequently occur that can endanger the continuation of therapy. Especially in pregnant patients with thromboembolic complications it may be difficult to find a suitable alternative anticoagulant when heparin-induced thrombocytopenia type II (HIT II) or allergic skin reactions occur. There are still limited data on the use of danaparoid in pregnancy.

Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004.

Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.

Safety and efficacy of danaparoid (Orgaran) use in children.

Immune-mediated heparin-induced thrombocytopenia (HIT) is an uncommon but serious complication of therapy with heparins. It affects all ages and requires replacement of the causative anticoagulant. However, information on alternative antithrombotic use in children with HIT is limited.

Results of a systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod, and/or coumarin explain the rapid shift in clinical practice during the 1990s.

Introduction: Randomized controlled trials evaluating treatment of acute, transient, but uncommon diseases are difficult to perform. The prothrombotic adverse drug reaction, heparin-induced thrombocytopenia (HIT), is such an example. During the mid-1980s, the defibrinogenating snake venom, ancrod (+/-warfarin, Canada), or coumarin (warfarin, Canada; phenprocoumon, Germany) alone, were often used to treat HIT.

Treatment of 51 pregnancies with danaparoid because of heparin intolerance.

Pregnant patients with acute venous thrombosis or a history of thrombosis may need alternative anticoagulation, when heparin intolerance occurs. Only limited data on the use of the heparinoid danaparoid are available in literature. We reviewed the use of danaparoid in 51 pregnancies of 49 patients identified in literature between 1981 and 2004.

The pharmacokinetics of fondaparinux sodium in healthy volunteers.

Objective: Fondaparinux sodium is the first in a new class of synthetic factor Xa inhibitors that binds reversibly with high affinity to antithrombin III. It has been investigated for the prevention and treatment of arterial and venous thrombotic disorders and approved for use at a dose of 2.5mg once daily in the prevention of venous thromboembolism in major orthopaedic surgery.

Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.

Aim: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis.

Methods: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody.

Heparin-induced thrombocytopenia in paediatric patients--a review of the literature and a new case treated with danaparoid sodium.

Unlabelled: The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fc gamma receptors. Cross-linking of multiple Fc gamma receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis.

Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators' Group.

This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.

Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172).

Heparin-induced thrombocytopenia (HIT) with thrombosis occurs in about 1 in 2,000 heparin-treated patients. The arterial or venous thromboses may threaten life and limb hence alternative anticoagulation is needed. Some alternative treatments are possible i.

Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoid.

We assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s.c.

Orgaran in heparin-induced thrombocytopenia.

Patients who develop heparin-induced thrombocytopenia (HIT) frequently need further anticoagulation to treat an ongoing thromboembolic problem or to prevent one. Orgaran (Org 10172), a low-molecular-weight (LMW) glycosaminoglycuronan, has shown a low frequency (10%) of cross-reactivity in vitro with sera containing the HIT antibody, in contrast to the much higher frequency of cross-reactivity (approximately 80%) shown by the LMW heparins. This paper summarises the results of intravenous or subcutaneous Orgaran treatment in 57 of 67 Australian patients, in whom the diagnosis of HIT was reasonably confirmed by exclusion of other causes of thrombocytopenia and by objective tests.

Pharmacokinetic considerations on Orgaran (Org 10172) therapy.

Pharmacokinetic investigations on Orgaran (Org 10172) have been conducted by monitoring the following biological effects: plasma anti-Xa, anti-IIa and IIa-generation-inhibiting (IIaGI) activities. In addition, a limited number of studies were conducted on the basis of concentrations of the No-affinity glycosaminoglyc(uron)an (NoA-GAG) fraction as determined by a competitive binding assay. In humans, widely different pharmacokinetic profiles for various biological effects were observed, with relatively short elimination half-lives for the anti-IIa and IIaGI activities of 4.

Interaction study between Org 10172, a low molecular weight heparinoid, and acetylsalicylic acid in healthy male volunteers.

Potential interactions between Org 10172 (Lomoparan, i.v. bolus injection of 3,250 anti-Xa units followed by 750 units twice daily s.

The influence of Org 10172, an antithrombotic heparinoid, on urinary blood loss after transurethral prostatectomy.

We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge; 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery.

ORG 10172: a low molecular weight heparinoid anticoagulant with a long half-life in man.

ORG 10172 is a heparinoid with mean molecular weight 6500 daltons. Intravenous bolus injections of ORG 10172 were compared with placebo and heparin injections in 91 separate studies in 83 healthy male subjects. 6400 units ORG 10172 produced a mean maximum change of 14.