phenprocoumon and Heart-Valve-Diseases

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aortic Valve; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Germany; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Phenprocoumon; Postoperative Complications; Prospective Studies; Survival Rate; Thromboembolism; Warfarin

Bleeding is the most common complication of oral anticoagulants, due to inadequate dosing.. This report describes the clinical course of a patient who developed severe bleeding under therapy with phenprocoumon, despite an INR in the lower therapeutic range. Strikingly, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors. Finally, sequencing part of the factor IX gene including nucleotide position c.110 revealed a hemizygous factor IX mutation c.110C > T p (Ala37Val).. In rare cases, missense mutations in factor IX propeptide are associated with severe bleeding complications. The substitution of alanin at position 37 to either valin or threonin (Ala37Val or Ala37Thr) leads to hypersensitivity to vitamin k antagonists.

Topics: Administration, Oral; Anticoagulants; Aortic Valve; DNA; DNA Mutational Analysis; Factor IX; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mutation; Patient Acuity; Phenprocoumon; Postoperative Hemorrhage; Tomography, X-Ray Computed

Bioprosthetic valve replacement is the treatment of choice in older patients with symptomatic severe aortic valve disease. Thrombosis of bioprosthetic valves has been considered a rare complication; however, in the presence of valvular obstruction, therapeutic consequences for the individual patient may be dramatic including repeat valve replacement or thrombolysis. We therefore evaluated oral anticoagulation with phenprocoumon as an alternative treatment for obstructive thrombosis of bioprosthetic valves. Six of 470 patients who had received a single stented bioprosthetic aortic valve from January 2007 through December 2008 at our hospital presented with obstructive bioprosthetic valve thrombosis within 14 months postoperatively. All 6 patients (1% of study population) had received a porcine valve (p = 0.1 vs pericardial), were hemodynamically stable, were in sinus rhythm, and were taking acetylsalicylic acid 100 mg/day. Echocardiography showed an increase in mean pressure gradient early postoperatively from 23.3 ± 4 to 57.0 ± 10 mm Hg (p <0.001). Five patients were started on phenprocoumon and followed for 114 ± 54 days, when mean pressure gradient had returned to 23.5 ± 6 mm Hg. No adverse events were observed during that period. One patient presenting with dyspnea and fever underwent emergency repeat valve replacement for suspected endocarditis, with histology showing long-term thrombosis of the explanted valve. In conclusion, oral anticoagulation with phenprocoumon represents a safe and effective treatment in clinically stable patients with obstructive thrombosis of bioprosthetic aortic valves, thus obviating repeat valve surgery or thrombolysis.

Topics: Aged; Anticoagulants; Aortic Valve; Bioprosthesis; Dose-Response Relationship, Drug; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Diseases; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Phenprocoumon; Retrospective Studies; Thrombosis; Treatment Outcome

Topics: Blood Coagulation Tests; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Phenprocoumon; Postoperative Complications; Thrombosis

Five hundred and four St. Jude Medical valves (SJM) were implanted in 435 patients between September 1978 and March 1982. There were 234 females and 201 males with a mean age of 52.8 +/- 10.1 years (range 12-83 years), who underwent 204 aortic, 163 mitral, 67 mitral plus aortic and one triple valve replacements. All patients were followed prospectively. Follow up was 100% complete and averaged 122.2 +/- 1.1 months for operative survivors. The total follow up for aortic patients was 1968.5, for mitral patients 1520.4, and for double valve replacement 573.9 pty. For the entire patient population the total follow up was 4080.8 pty. Early mortality was 2% after aortic, 4.3% after mitral and 5.9% after mitral plus aortic valve replacement. There were 68 late deaths representing a linearized incidence of 1.37%/pty in the aortic, 1.71%/pty in the mitral and 2.61%/pty in the double valve replacement groups. The corresponding cumulative survival after ten years at risk was 85% in the aortic, 78% in the mitral and 72% in the double valve replacement groups. The ten year event-free survival was 64% in the aortic, 57% in the mitral and 47% in the double valve replacement groups. The linearized incidence for thromboembolic events was 3.71%/pty taking all events into account, and 2.67%/pty taking only the first or most severe of several events into account for aortic, 5.1%/pty and 4.08%/pty for mitral, and 6.62%/pty and 5.40%/pty for double replacements, respectively. There were two cases of valve thrombosis, both with proven inadequate anticoagulation. When the prothrombin times measured with the different thromboplastize used in this patient group were converted to INR, the so far homogeneous values could be separated into three groups: INR = 3.0 to 4.5, 2.5 to 3.2 and 1.8 to 2.7. Low INR values caused only a marginal increase in the rate of embolism but a highly significant decrease in the rate of bleeding. These results suggest that the generally recommended INR of 3.0 to 4.5 is too high for the SJM. A large, multicenter, prospective randomized study is therefore proposed to establish the safe INR levels with low intensity anticoagulation after SJM implantation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Prothrombin; Prothrombin Time; Survival Rate; Thromboembolism