scholarly journals Immediate high-dose intravenous immunoglobulins followed by direct thrombin-inhibitor treatment is crucial for survival in Sars-Covid-19-adenoviral vector vaccine-induced immune thrombotic thrombocytopenia VITT with cerebral sinus venous and portal vein thrombosis

2021 ◽  
Author(s):  
Tilmann Graf ◽  
Thomas Thiele ◽  
Randolf Klingebiel ◽  
Andreas Greinacher ◽  
Wolf-Rüdiger Schäbitz ◽  
...  
Keyword(s):  
Portal Vein ◽  
Adenoviral Vector ◽  
Intravenous Immunoglobulins ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
High Dose ◽  
Vector Vaccine ◽  
Vein Thrombosis ◽  
Cerebral Sinus ◽  
Inhibitor Treatment

scholarly journals Successful Treatment of Vaccine-Induced Immune Thrombotic Thrombocytopenia in a 26-Year-Old Female Patient

2021 ◽  
pp. 1-4
Author(s):  
Marcel Kemper ◽  
Georg Lenz ◽  
Rolf Michael Mesters
Keyword(s):  
Female Patient ◽  
Treatment Options ◽  
Anticoagulation Therapy ◽  
Intravenous Immunoglobulins ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Vein Thrombosis ◽  
Medical Facilities ◽  
Deep Vein ◽  
Improve Patient

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has already been described after vaccination with ChAdOx2 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen). However, less knowledge so far has been gained about optimal therapeutic regimens in VITT-suspected patients. Here, we report the case of a 26-year-old female patient, who developed bilateral deep vein thrombosis in the lower legs and severe thrombocytopenia after ChAdOx2 nCov-19 vaccination. After initial anticoagulation therapy regimens including fondaparinux, apixaban, and danaparoid failed, the patient was successfully treated with high-dose intravenous immunoglobulins in combination with parental anticoagulation therapy with argatroban. As vaccination against severe acute respiratory syndrome coronavirus 2 affects billions of people worldwide, medical facilities and hospitals have to be prepared and provide effective treatment options in VITT-suspected patients, including rapid application of high-dose intravenous immunoglobulins, to improve patient outcomes.

scholarly journals Direct Thrombin Inhibitor Resistance and Possible Mechanisms

2016 ◽  
Vol 51 (11) ◽  
pp. 922-927 ◽  
Author(s):  
Maria Cardinale ◽  
Michael Ha ◽  
Michael H. Liu ◽  
David P. Reardon
Keyword(s):  
International Normalized Ratio ◽  
Resistance Mechanisms ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Inhibitor Resistance ◽  
Deep Vein

Objective To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT. Indications for bivalirudin were anticoagulation in intra-aortic balloon pump, treatment of deep vein thrombosis, and heparin-induced thrombocytopenia with thrombosis. Target aPTT was achieved between 25.5 and 134 hours after initiation despite appropriate titration intervals per protocol. Discussion Bivalirudin is a direct thrombin inhibitor frequently used off-label for the medical management of heparin-induced thrombocytopenia. It typically exhibits predictable, dose-dependent anticoagulation. Heparin-induced thrombocytopenia was suspected in 2 of the 3 cases and confirmed in 1. In all 3 patients, target aPTT was initially achieved with doses between 0.456 and 1.0 mg/kg/h after a median of 30.7 hours; up to 1.8 mg/kg/h was required to maintain therapeutic aPTT. In 2 of the cases, the international normalized ratio also increased unexpectedly upon achievement of therapeutic aPTT values. Conclusion Direct thrombin inhibitors may be subject to resistance mechanisms similar to those previously described in patients receiving heparin. The anticoagulation status of these patients remains unknown.

High-dose but not low-dose enoxaparin substantially improves survival in cirrhotic patients with portal vein thrombosis

2018 ◽  
Vol 68 ◽  
pp. S704
Author(s):  
L. Turco ◽  
N. Gualandi ◽  
R. Vukotic ◽  
M. Bianchini ◽  
F. Schepis ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Low Dose ◽  
High Dose ◽  
Vein Thrombosis ◽  
Cirrhotic Patients

Pharmacokinetics and Pharmacodynamics of Melagatran, a Novel Synthetic LMW Thrombin Inhibitor, in Patients with Acute DVT

1999 ◽  
Vol 81 (03) ◽  
pp. 358-363 ◽  
Author(s):  
H. Eriksson ◽  
L. Frison ◽  
P. O. Hansson ◽  
P. Held ◽  
M. Holmström ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Thrombin Inhibitor ◽  
High Dose ◽  
Vein Thrombosis ◽  
The Mean ◽  
Clinically Significant ◽  
Deep Vein ◽  
Dose Levels ◽  
Infusion Period ◽  
Different Doses

SummaryForty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 μmol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.

A Dose-ranging Study of the Oral Direct Thrombin Inhibitor, Ximelagatran, and Its Subcutaneous Form, Melagatran, Compared with Dalteparin in the Prophylaxis of Thromboembolism after Hip or Knee Replacement: METHRO I

2002 ◽  
Vol 87 (02) ◽  
pp. 231-237 ◽  
Author(s):  
Ann-Christin Arfwidsson ◽  
Lars Frison ◽  
Ulf Eriksson ◽  
Anders Bylock ◽  
Peter Kälebo ◽  
...  
Keyword(s):  
Knee Replacement ◽  
Dose Response ◽  
Active Form ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Oral Direct Thrombin Inhibitor ◽  
Vein Thrombosis ◽  
Parallel Group ◽  
Oral Availability

SummaryThe novel, oral direct thrombin inhibitor, ximelagatran (formerly H 376/95), represents an advance in antithrombotic therapy through its oral availability. After oral administration, ximelagatran is converted to its active form, melagatran. Melagatran can also be administered subcutaneously (sc). The results from the first clinical study with ximelagatran are reported. In this randomized, parallel-group, controlled study, 103 patients scheduled for elective total hip or total knee replacement received sc melagatran (1, 2 or 4 mg bid) for 2 days commencing immediately before surgery, followed by oral ximelagatran (6, 12 or 24 mg bid) for 6-9 days. Another 33 patients received dalteparin 5000 IU sc once daily, started the evening before surgery, for 8-11 days. At bilateral venography, deep vein thrombosis was found in 20.5% (16/78) of patients who had received sc melagatran and oral ximelagatran and in 18.5% (5/27) of patients in the dalteparin group. The study did not evaluate a dose-response for efficacy, and no differences between the three dose levels of melagatran and ximelagatran were shown. No pulmonary embolism was diagnosed during treatment. Total bleeding in the sc melagatran plus oral ximelagatran groups showed no dose-response and was similar to that seen in the dalteparin group. The pharmacokinetic properties of melagatran in the surgery patients were consistent with those observed for healthy subjects, and the APTT ratio, which increased non-linearly with plasma melagatran concentration, showed a consistent concentration-effect relationship during the treatment period. Ximelagatran and melagatran were well tolerated. In conclusion, ximelagatran and its active form melagatran appear to be promising agents for the prevention of venous thromboembolism following orthopaedic surgery.

Sign in / Sign up

Export Citation Format

Share Document