Thrombin inhibitors direct

Direct thrombin inhibitors belong to the group of anticoagulants and are used for the prophylaxis or therapy of thromboembolism.

One of them is dabigatran (Pradaxa®). This is an oral thrombin inhibitor belonging to the group of NOAK (New oral anticoagulants) or DOAK (Direct oral anticoagulants). The thrombin inhibitor is eliminated up to 80% renally. Due to the predominantly renal excretion, regular monitoring of renal function is required before and during therapy.

Antidote: The antidote is Idarucizumab (trade name Praxbind. Dosage: 2 x 2.5 g i.v. (Bischoff 2016)

Contraindication:

• renal insufficiency (special caution is required with a creatinine clearance of less than 30 ml/ min, as severe bleeding may occur during treatment with direct thrombin inhibitors)
• Gravidity and lactation
• otherwise s. manufacturer's data

Side effects:

• gastrointestinal symptoms
• severe bleeding in case of renal insufficiency (see above)

This medicine may alsointeract with the following medications:

• cyclosporine
• Levostatin
• Simvastatin
• Tacrolimus
• triazole antimycotics
• among others (Herald 2918)

Dosages:

For thromboembolic prophylaxis after hip or knee TEP, a dosage of 1 x 150 mg to 220 mg / d should be started 1 h before the surgical procedure, provided that the glomerular filtration rate is > 80 ml / min (Jähne 2017).

The following dosage is recommended for thromboembolic prophylaxis in existing atrial fibrillation:

• 2 x 150 mg/d. (with corresponding risk factors, dose reduction if necessary).
• For the therapy of deep vein thrombosis or pulmonary embolism the manufacturer's instructions should be followed
• Patients over 75 years of age and also patients with moderately limited renal insufficiency should receive a dosage reduced to 150 mg/day (Encke 2015).

Surgery under DOAK: If surgery becomes necessary under therapy with direct thrombin inhibitors, it may be possible to perform surgery without bridging, unlike with vitamin K antagonists. An exception are patients with renal insufficiency. In these patients, dabigatran should be discontinued 1 - 4 days before the planned operation.

Direct thrombin inhibitors belong to the group of anticoagulants and are used for the prophylaxis or therapy of thromboembolism. They include:

• Dabigatran, trade name Pradaxa® and the
• Argatroban (i.v. applicable)

Dabigatran belongs as an oral thrombin inhibitor to the group of NOAKs (New oral anticoagulants) or DOAKs (Direct oral anticoagulants). The thrombin inhibitor is eliminated up to 80% renally. Due to the predominantly renal excretion, regular monitoring of renal function is necessary before and during therapy (Herold 2918).

Antidote: The antidote is Idarucizumab (Praxbind®) Dosage: 2 x 2.5 g i.v. (Bischoff 2016)

Indications for treatment with direct thrombin inhibitors are: - Thromboembolic prophylaxis after hip or knee - TEP - Thromboembolic prophylaxis in non-valvular atrial fibrillation - Therapy of deep vein thrombosis - Therapy of pulmonary embolism. Contraindication: - renal insufficiency (special caution is required with a creatinine clearance of less than 30 ml/min, as severe bleeding can occur with treatment with direct thrombin inhibitors) - pregnancy and lactation - otherwise see otherwise see manufacturer's instructions. Side effects: - gastrointestinal symptoms - severe bleeding in renal failure (see above).

Interactions may occur with the following drugs: - ciclosporin - levostatin - simvastatin - tacrolimus - triazole - antifungals - etc.

Dosages:

• For thromboembolic prophylaxis after hip or knee TEP, a dosage of 1 x 150 mg to 220 mg / d should be started 1 h before the surgical procedure, provided that the glomerular filtration rate is > 80 ml / min (Jähne 2017).
• The following dosage is recommended for thromboembolic prophylaxis in case of existing atrial fibrillation: - 2 x 150 mg/day. (with corresponding risk factors, dose reduction if necessary).
• For the therapy of deep vein thrombosis or pulmonary embolism the manufacturer's instructions should be followed. Patients over 75 years of age and also patients with moderately limited renal insufficiency should receive a dosage reduced to 150 mg/d (Encke 2015). If a surgical intervention becomes necessary under a therapy with direct thrombin inhibitors, this can - in contrast to the vitamin K antagonists - possibly be performed without bridging. Patients with renal insufficiency are an exception. In these patients, dabigatran should be discontinued 1 - 4 days before the planned operation.

Indications for treatment with direct thrombin inhibitors are:

• Thromboembolic prophylaxis after hip or knee TEP
• Thromboembolism prophylaxis in non-valvular atrial fibrillation
• Therapy of deep vein thrombosis
• Therapy of pulmonary embolism

Idarucizumab (antidote for dabigatran = thrombin inhibitor)) Idarucizumab is a humanized monoclonal antibody fragment that abolishes the anticoagulant effect of Dabigatran. The affinity of Idarucizumab is about 350 times greater for dabigatran than for thrombin. Idarucizumab binds specifically to dabigatran. Idarucizumab has no known effects on anti-Xa inhibitors or other anticoagulants. Idarucizumab is renally eliminated and showed no procoagulant effects in the pivotal studies. Idarucizumab has been used in clinical practice for several years. Several cases have been described in the literature to date in which life-threatening bleeding under dabigatran has been successfully treated with Idarucizumab.

1. Bischoff M (2016) Antidote Idarucizumab: "Airbag" for the NOAK Dabigatran. German medical journal (19) A 946
2. Encke A et al. (2015) S3- Guideline: Prophylaxis of venous thromboembolism (VTE) AWMF Guidelines- Register No. 003/001
3. Herold G et al (2018) Internal Medicine. Herold Publisher SS 834, 836
4. Jähne J et al (2017) What is new in surgery? Reports on surgical education and training. Ecomed Storck Publishing House S 388