Table E3.
Additional information on thromboembolic events.
| Patient | Study | Onset Day* |
Indication for VKA | Event Consistent With Indication for VKA† |
Actual Dose, IU/kg |
Receiving Anticoagulant at Event |
Additional Risk Factors‡4 |
|---|---|---|---|---|---|---|---|
| 4F-PCC | |||||||
| K1 | Bleeding | 1 | Portal veinthrombosis | Yes | 50.0 | No | CAD, DM, HTN, end-stage renal disease, obesity |
| K2 | Bleeding | 1 | DVT | Yes | 35.0 | No | AF, CHF, DM, HTN, CAD |
| K3 | Surgery | 1 | Mitral valve replacement and AF | Yes | 50.0 (overdose, should have been 25.0) | No | Cardiomyopathy, CHF, HTN, medication error, DVT left arm, atrial flutter |
| K4 | Surgery | 6 | DVT | No | 25.0 | Yes | Metastatic prostate cancer |
| K5 | Surgery | 7 | AF | No | 25.0 | No | End-stage renal disease, hemodialysis, HTN, CAD, stroke |
| K6 | Bleeding | 9 | DVT | Yes | 50.0 | No | HTN |
| K7 | Bleeding | 9 | AF/St Jude’s valve | Yes | 35.0 | No | Blood transfusions, CAD, CVA, HTN, MI |
| K8 | Bleeding | 10 | AF | Yes | 25.0 | Yes | Blood transfusions, CHF, DVT/PE, thrombocytosis |
| K9 | Surgery | 10 | AF | Yes | 25.0 | Yes | CAD, CHF, HTN, DM, atrial flutter, chronic renal insufficiency, chronic kidney disease stage 3 |
| K9 | Surgery | 11 | As above | No | As above | As above | As above |
| K10 | Surgery | 12 | DVT | Yes | 50.0 | No | PE |
| K11 | Bleeding | 13 | AF | No | 25.0 | No | CAD, HTN, immobility (multiple fractures), head trauma, MI |
| K11 | Bleeding | 29 | As above | No | As above | No | As above |
| K12 | Surgery | 19 | AF | No | 25.0 | No | Atrial flutter, PAF with RVR, sick sinus syndrome, HTN, right breast ductal carcinoma |
| K13 | Bleeding | 38 | AF | No | 25.0 | No | Cardiomyopathy, CVA, DM, HTN |
| K14 | Bleeding | 43 | AF | Yes | 35.0 | No | CAD, CHF, HTN, TIA |
| Plasma | |||||||
| P1 | Bleeding | 1 | AF | No | 4.4 | No | CAD, CHF and cardiomyopathy, EF of 27%, HTN, MI |
| P1 | Bleeding | 4 | As above | No | As above | No | As above |
| P2 | Bleeding | 1 | AF | No | 6.0 | No | CAD, CHF, cardiomyopathy, EF of 68%, CVA DM, HTN, ischemic colitis, SMA-occlusion hx |
| P3 | Bleeding | 1 | Aortic valve replacement | No | 13.5 | No | CAD, CHF, DM, HTN, MI |
| P4 | Bleeding | 1 | AF | Yes | 17.7 | No | HTN, DM |
| P5 | Bleeding | 1 | AF | Yes | 6.5 | Yes | HTN, CAD, CHF, mitral valve incompetence, MI |
| P6 | Surgery | 1 | DVT | No | 12 | No | Hypercoagulable state of unknown cause |
| P7 | Surgery | 1 | DVT | Yes | 7 | No | HTN, PE, obesity |
| P8 | Surgery | 2 | AF | Yes | 11 | No | CHF, HTN |
| P9 | Surgery | 4 | AF | No | 10 | No | Severe AS, DM, obesity, EF 25%, hypotension |
| P10 | Surgery | 6 | AF | Yes | 12 | Yes | CHF |
| P11 | Bleeding | 13 | AF | No | 9.9 | Yes | CAD, stent placement |
| P12 | Surgery | 16 | AF | No | 10 | No | CHF, immobility |
| P13 | Bleeding | 22 | AF | Yes | 10.0 | Yes | DM, ARF and CRF, CHF, HTN, obesity |
| P14 | Surgery | 56§ | DVT | No | 10 | No | Intermittent irregular heart rhythm, HTN, CAD, DM |
CAD, Coronary artery disease; DM, diabetes mellitus; HTN, hypertension; CHF, congestive heart failure; PAF, paroxysmal atrial fibrillation; RVR, rapid ventricular response; EF, ejection fraction; SMA, superior mesenteric artery; hx, history; AS, aortic stenosis; ARF, acute renal failure; CRF, chronic renal failure.
The vena cava filter insertion (K4) was not considered a thromboembolic event by the lead author. The Food and Drug Administration assessed some of the AEs and thromboembolic events differently from the study investigators/SAB, resulting in a difference in the numbers of thromboembolic events reported in the package insert for the 4F-PCC in the United States (Kcentra)19 compared with published study results.14, 15
Onset study day of thromboembolic event, day of study product infusion is day 1.
Thromboembolic event considered consistent with the patient’s original VKA indication by the lead author.
In addition to indication for VKA treatment.
Acute CVA was diagnosed on day 56 but included in the thromboembolic event analysis because of uncertain timing related to the start of the event.