Roel Vink - Academia.edu (original) (raw)

Papers by Roel Vink

Research paper thumbnail of Prevention and treatment of bleeding by pro-hemostatic treatment strategies

Wiener medizinische Wochenschrift (1946), 2003

Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemos... more Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. Pro-hemostatic interventions appear to be effective in reducing peri-operative blood loss and reducing transfusion requirements in specific situations and may be helpful adjuncts in the management of severe spontaneous and post-operative bleeding. The risk of a higher incidence of thrombotic complications associated with the use of pro-hemostatic therapy is unknown but seems not to be very high in clinical practice. There is a need for more systematic and adequately controlled clinical observations to better establish the efficacy and safety of pro-hemostatic interventions.

Research paper thumbnail of Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME)

Transfusion, 2014

Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy ... more Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion-related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP. A multicenter randomized open-label trial with blinded endpoint evaluation was performed in critically ill patients with a prolonged international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a central venous catheter, percutaneous tracheostomy, chest tube, or abscess drainage were eligible. Patients with clinically overt bleeding, thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients were randomly assigned to omitting or administering a prophylactic transfusion of FFP (12 mL/kg). Outcomes were occurrence of postprocedural bleeding complications, INR correction, and occurrence of lung injury. Due to slow inclusion, the trial was stopped before the predefined target enrollment was reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP transfusion. Incidence of bleeding did not differ between groups, with a total of one major and 13 minor bleedings (p = 0.08 for noninferiority). FFP transfusion resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No differences in lung injury scores were observed. In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not.

Research paper thumbnail of The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: A meta-analysis

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Management of bleeding disorders by prohemostatic therapy

International Journal of Hematology, 2002

Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioratio... more Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. These treatment strategies may be applied to specifically correct a defect in one of the pathways of coagulation, but have in some situations also been shown to be effective in reducing bleeding in patients without a primary defect in coagulation. Besides the transfusion of platelets in case of thrombocytopenia or severe platelet disorders, a pharmacological improvement of primary hemostasis may be achieved by the administration of desmopressin. The administration of DDAVP results in a marked increase in the plasma concentration of Von Willebrand factor (and associated coagulation factor VIII) and (also by yet unexplained additional mechanisms) a remarkable potentiation of primary hemostasis as a consequence. DDAVP is used for the prevention and treatment of bleeding in patients with von Willebrand disease or mild hemophilia A, and further in patients with an impaired function of primary hemostasis, such as in patients with uremia, liver cirrhosis or in patients with aspirin-associated bleeding. Based on the current insight that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII(a) pathway, recombinant factor VIIa has been developed as a prohemostatic agent and has recently become available for clinical use. Indeed, in uncontrolled clinical studies this compound has been shown to exert a potent procoagulant activity and appeared to be highly effective in the prevention and treatment of bleeding, although most experience so far has been obtained in patients with severe and complicated coagulation defects. At present, a more general use of this agent for bleeding patients without an apparent coagulation defect is the subject of a number of ongoing clinical trials. Agents that exert anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The pro-hemostatic effect of these agents proceeds not only by the inhibition of fibrinolysis (thereby shifting the procoagulant/anticoagulant balance towards a more procoagulant state), but also due to a protective effect on platelets, as has been demonstrated at least for aprotinin. The mechanism of this platelet-protective effect has, besides a potential prevention of plasmin-mediated loss of platelet receptors not been elucidated. Whether the pro-hemostatic effect of the anti-fibrinolytic agents will eventually result in a higher incidence of thromboembolic complications is still a matter of debate (see further), however, this has so far not been shown in straightforward clinical trials.

Research paper thumbnail of Challenges in managing anticoagulant therapy in patients with heart valve prostheses

Expert Review of Cardiovascular Therapy, 2007

There is a wide array of recommendations for the management of anticoagulant therapy in patients ... more There is a wide array of recommendations for the management of anticoagulant therapy in patients with mechanical heart valves. The optimal intensity of vitamin K antagonists, management of patients during noncardiac surgery and use of anticoagulants during pregnancy are all ongoing matters of debate. In this review, we discuss the various studies on these topics and the different guidelines. Based on these, literature recommendations for daily clinical practice are formulated.

Research paper thumbnail of Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers

British Journal of Haematology, 2004

We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor X... more We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 microg/kg intravenous (i.v.)] (n = 6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 microg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.

Research paper thumbnail of Recurrent Thromboembolism After Treatment With Vitamin K Antagonists

Archives of Internal Medicine, 2003

Research paper thumbnail of Risk of Thromboembolism and Bleeding After General Surgery in Patients With Atrial Fibrillation

The American Journal of Cardiology, 2005

We provide insight into the risk of perioperative thromboembolism and bleeding in patients who ha... more We provide insight into the risk of perioperative thromboembolism and bleeding in patients who have atrial fibrillation, use anticoagulants, and undergo a surgical procedure. Ninety-four patients underwent 121 noncardiac operations during a mean follow-up of 29 months. There was a 3.6-fold increased risk for all bleeding complications within 1 month after surgery compared with the control period (95% confidence interval 1.05 to 12.0). No thromboembolic event occurred in the first month after surgery compared with 11 events in the remaining period (0.4% per month).

Research paper thumbnail of Prevention and treatment of bleeding by pro-hemostatic treatment strategies

Wiener medizinische Wochenschrift (1946), 2003

Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemos... more Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. Pro-hemostatic interventions appear to be effective in reducing peri-operative blood loss and reducing transfusion requirements in specific situations and may be helpful adjuncts in the management of severe spontaneous and post-operative bleeding. The risk of a higher incidence of thrombotic complications associated with the use of pro-hemostatic therapy is unknown but seems not to be very high in clinical practice. There is a need for more systematic and adequately controlled clinical observations to better establish the efficacy and safety of pro-hemostatic interventions.

Research paper thumbnail of Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME)

Transfusion, 2014

Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy ... more Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion-related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP. A multicenter randomized open-label trial with blinded endpoint evaluation was performed in critically ill patients with a prolonged international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a central venous catheter, percutaneous tracheostomy, chest tube, or abscess drainage were eligible. Patients with clinically overt bleeding, thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients were randomly assigned to omitting or administering a prophylactic transfusion of FFP (12 mL/kg). Outcomes were occurrence of postprocedural bleeding complications, INR correction, and occurrence of lung injury. Due to slow inclusion, the trial was stopped before the predefined target enrollment was reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP transfusion. Incidence of bleeding did not differ between groups, with a total of one major and 13 minor bleedings (p = 0.08 for noninferiority). FFP transfusion resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No differences in lung injury scores were observed. In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not.

Research paper thumbnail of The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: A meta-analysis

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Management of bleeding disorders by prohemostatic therapy

International Journal of Hematology, 2002

Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioratio... more Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. These treatment strategies may be applied to specifically correct a defect in one of the pathways of coagulation, but have in some situations also been shown to be effective in reducing bleeding in patients without a primary defect in coagulation. Besides the transfusion of platelets in case of thrombocytopenia or severe platelet disorders, a pharmacological improvement of primary hemostasis may be achieved by the administration of desmopressin. The administration of DDAVP results in a marked increase in the plasma concentration of Von Willebrand factor (and associated coagulation factor VIII) and (also by yet unexplained additional mechanisms) a remarkable potentiation of primary hemostasis as a consequence. DDAVP is used for the prevention and treatment of bleeding in patients with von Willebrand disease or mild hemophilia A, and further in patients with an impaired function of primary hemostasis, such as in patients with uremia, liver cirrhosis or in patients with aspirin-associated bleeding. Based on the current insight that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII(a) pathway, recombinant factor VIIa has been developed as a prohemostatic agent and has recently become available for clinical use. Indeed, in uncontrolled clinical studies this compound has been shown to exert a potent procoagulant activity and appeared to be highly effective in the prevention and treatment of bleeding, although most experience so far has been obtained in patients with severe and complicated coagulation defects. At present, a more general use of this agent for bleeding patients without an apparent coagulation defect is the subject of a number of ongoing clinical trials. Agents that exert anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The pro-hemostatic effect of these agents proceeds not only by the inhibition of fibrinolysis (thereby shifting the procoagulant/anticoagulant balance towards a more procoagulant state), but also due to a protective effect on platelets, as has been demonstrated at least for aprotinin. The mechanism of this platelet-protective effect has, besides a potential prevention of plasmin-mediated loss of platelet receptors not been elucidated. Whether the pro-hemostatic effect of the anti-fibrinolytic agents will eventually result in a higher incidence of thromboembolic complications is still a matter of debate (see further), however, this has so far not been shown in straightforward clinical trials.

Research paper thumbnail of Challenges in managing anticoagulant therapy in patients with heart valve prostheses

Expert Review of Cardiovascular Therapy, 2007

There is a wide array of recommendations for the management of anticoagulant therapy in patients ... more There is a wide array of recommendations for the management of anticoagulant therapy in patients with mechanical heart valves. The optimal intensity of vitamin K antagonists, management of patients during noncardiac surgery and use of anticoagulants during pregnancy are all ongoing matters of debate. In this review, we discuss the various studies on these topics and the different guidelines. Based on these, literature recommendations for daily clinical practice are formulated.

Research paper thumbnail of Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers

British Journal of Haematology, 2004

We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor X... more We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 microg/kg intravenous (i.v.)] (n = 6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 microg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.

Research paper thumbnail of Recurrent Thromboembolism After Treatment With Vitamin K Antagonists

Archives of Internal Medicine, 2003

Research paper thumbnail of Risk of Thromboembolism and Bleeding After General Surgery in Patients With Atrial Fibrillation

The American Journal of Cardiology, 2005

We provide insight into the risk of perioperative thromboembolism and bleeding in patients who ha... more We provide insight into the risk of perioperative thromboembolism and bleeding in patients who have atrial fibrillation, use anticoagulants, and undergo a surgical procedure. Ninety-four patients underwent 121 noncardiac operations during a mean follow-up of 29 months. There was a 3.6-fold increased risk for all bleeding complications within 1 month after surgery compared with the control period (95% confidence interval 1.05 to 12.0). No thromboembolic event occurred in the first month after surgery compared with 11 events in the remaining period (0.4% per month).