Table 2.

Details of patients with thromboembolic events (pooled safety population).

Patient	Study	Onset Day*	Age	Indication for VKA	Standardized Term	SAE	Causality†		Baseline INR	Death (Day)
							Investigator	SAB
4F-PCC
K1	Bleeding	1	66	Portal vein thrombosis	Thrombosis in device (fistula clot/thrombosis)	No	Yes	Not assessed	12.7	Yes (26)
K2	Bleeding	1	73	DVT	Venous thrombosis calf vein	No	Yes	Not assessed	5.4	No
K3	Surgery	1	64	Mitral valve replacement and AF	Ischemic stroke	Yes	Yes	Yes	2.7	No
K4	Surgery	6	78	DVT	Vena cava filter insertion‡	No	No	Not assessed	3.1	No
K5	Surgery	7	62	AF	Catheter-related complication (poor flow in dialysis catheter)	No	No	Not assessed	3.6	No
K6	Bleeding	9	54	DVT	Venous thrombosis limb (basilic vein clot at PICC line site)	No	No	Not assessed	9.2	No
K7	Bleeding	9	82	AF/St Jude’s valve	Ischemic stroke	Yes	No	Yes	4.4	No
K8	Bleeding	10	85	AF	Ischemic stroke	Yes	No	No	3.8	No
K9	Surgery	10	89	AF	CVA	No	No	Not assessed	2.2	No
K9	Surgery	11	As above	As above	Venous thrombosis limb (radial vein)	No	Yes	Not assessed	As above	As above
K10	Surgery	12	51	DVT	Microthrombosis of toes	Yes	Yes	Not confirmed as TEE	17	No
K11	Bleeding	13	80	AF	DVT right leg	Yes	Yes	Yes	2.2	No
K11	Bleeding	29	As above	As above	DVT left leg	Yes	No	Yes	As above	As above
K12	Surgery	19	90	AF	DVT	Yes	Yes	Yes	3.7	No
K13	Bleeding	38	88	AF	MI	Yes	No	Not confirmed as TEE	2.4	Yes (38)
K14	Bleeding	43	89	AF	Ischemic stroke	Yes	Yes	No	4.5	Yes (46)
Plasma
P1	Bleeding	1	77	AF	Myocardial ischemia	Yes	Yes	Yes	2.0	No
P1	Bleeding	4	As above	As above	Thrombophlebitis	No	No	Not assessed	As above	No
P2	Bleeding	1	70	AF	Myocardial ischemia	Yes	Yes	Yes	3.1	No
P3	Bleeding	1	64	Aortic valve replacement	Acute MI	No	Yes	Not assessed	7.4	No
P4	Bleeding	1	75	AF	CVA	No	No	Not assessed	>3.99	No
P5	Bleeding	1	79	AF	Thrombosis in device (clotted NG tube)	No	No	Not assessed	2.8	No
P6	Surgery	1	75	DVT	Acute MI	Yes	No	Yes	5.9	No
P7	Surgery	1	59	DVT	DVT	Yes	Yes	Yes	2.1	No
P8	Surgery	2	85	AF	Embolic cerebral infarction	Yes	Yes	Yes	5.6	Yes (13)
P9	Surgery	4	61	AF	Acute MI	Yes	No	Yes	2.2	Yes (8)
P10	Surgery	6	50	AF	TIA	No	No	Not assessed	4.0	No
P11	Bleeding	13	68	AF	MI	Yes	No	No	2.5	No
P12	Surgery	16	92	AF	PE	Yes	No	Not confirmed as TEE	2.5	Yes (16)
P13	Bleeding	22	78	AF	CVA	Yes	No	No	3.0	No
P14	Surgery	56§	77	DVT	Acute CVA	Yes	No	No	2.1	No

SAE, Serious adverse event; SAB, Safety adjudication board; INR, international normalized ratio; DVT, deep venous thrombosis; AF, atrial fibrillation; PICC, peripheral into central circulation; CVA, cerebrovascular accident; MI, myocardial infarction; NG, nasogastric; TIA, transient ischemic attack; PE, pulmonary embolism.

^*Onset study day of thromboembolic event, day of study product infusion is day 1.

^†No: event deemed unrelated to the study product in the opinion of the investigator/SAB. Yes: event deemed at least possibly related to the study product in the opinion of the investigator/SAB. SAB evaluated only events that were SAEs and did not assess causality if the event was not confirmed as a thromboembolic one.

^‡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 adverse events 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}

^§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.