Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon.

OBJECTIVES: Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect. DESIGN: Prospective ex-vivo investigation. SETTING: University hospital. PARTICIPANTS: Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon. INTERVENTIONS: Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments. MEASUREMENTS AND MAIN RESULTS: Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01). CONCLUSIONS: Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.

Patients with severe aortic valve stenosis and impaired platelet function benefit from preoperative desmopressin infusion.

BACKGROUND: Patients with severe aortic valve stenosis have a markedly reduced platelet function as measured by a prolonged collagen adenosine diphosphate closure time (CADP-CT) determined by the platelet function analyzer PFA-100. We hypothesized that such patients may benefit from desmopressin when they present with prolonged CADP-CT due to the specific action of desmopressin on von Willebrand factor (VWF) and CADP-CT. METHODS: In this double-blind, randomized placebo controlled trial, 43 patients undergoing aortic valve replacement (due to severe aortic valve stenosis with CADP-CT>170 seconds) were given desmopressin 0.3 µg/kg or saline intravenously after induction of anesthesia. Measurement of CADP-CT, factor VIII activity, von Willebrand factor antigen, GpIb binding activity, ristocetin cofactor activity, collagen-binding activity, and multimers were performed after induction of anesthesia, one hour after desmopressin infusion, and 24 hours postoperatively. RESULTS: In the majority of patients, baseline values of von Willebrand factor related indices were normal, but increased one hour after infusion of desmopressin by 73% to 90% as compared with placebo. Selective loss of high molecular weight multimers was seen only in a minority of patients. The CADP-CT was greater than 170 seconds in 92% of screened patients, and desmopressin shortened CADP-CT by 48% versus baseline and reduced postoperative blood loss by 42% (p<0.001). CONCLUSIONS: Prolonged CADP-CT indicates platelet dysfunction in severe aortic valve stenosis, and can guide the use of desmopressin as an effective prohemostatic agent in patients with severe aortic valve stenosis.

Platelet dysfunction in outpatients with left ventricular assist devices.

BACKGROUND: Thromboembolic and bleeding complications in outpatients with a left ventricular assist device are common and can be detrimental. A meticulous balance between anticoagulant and procoagulant factors is therefore crucial. However, in contrast to routinely performed plasmatic coagulation tests, platelet function is hardly ever monitored although recent reports indicated platelet dysfunction. We therefore differentially evaluated platelet function with four commonly used point-of-care devices. METHODS: In a cross-sectional design platelet function was assessed in 12 outpatients and 12 healthy matched volunteers using thrombelastography platelet mapping, thromboelastometry, platelet function analyzer, and a new whole blood aggregometer (Multiplate). RESULTS: Phenprocoumon produced an international normalized ratio of 3.5. It was associated with a twofold prolongation in the thromboelastometry clotting time (p < 0.001). Platelet function under high shear was severely compromised: collagen adenosine diphosphate closure times were 2.5-fold longer in patients than in volunteers (p < 0.001), and 50% of patients had maximal collagen adenosine diphosphate closure time values. Although antigen levels of von Willebrand factor were 80% higher in patients (p < 0.001), von Willebrand factor-ristocetin was subnormal in 5 of 12 patients. Ristocetin-induced aggregation was also threefold higher in volunteers (p < 0.001), indicating an additional functional defect of platelets affecting the glycoprotein Ib-von Willebrand factor axis. The von Willebrand factor multimer pattern in patients also appeared abnormal. CONCLUSIONS: Multimodal antiplatelet monitoring showed markedly impaired platelet function in patients with a left ventricular assist device. Platelet dysfunction under high shear rates and abnormal ristocetin-induced aggregation is only partly attributable to low von Willebrand factor activity. These findings resemble the acquired von Willebrand syndrome that is associated with microaggregate formation and enhanced bleeding.