J Curr Surg

Journal of Current Surgery, ISSN 1927-1298 print, 1927-1301 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Curr Surg and Elmer Press Inc

Journal website https://www.currentsurgery.org

Case Report

Volume 12, Number 1, March 2022, pages 15-20

Perioperative Management of Hemophilia A With Recombinant VIII-SingleChain: A Case Series

Figure 1. Real-time FVIII activity levels over time for (a) case 1, (b) case 2, (c) case 3, and (d) case 4, measured from the first dose of rVIII-SingleChain. Real-time FVIII activity was measured using the OSA (black circles with solid black lines). Stored plasma samples were used to measure FVIII activity using the OSA (gray circles with solid gray lines) and the CSA (white diamonds with solid gray lines). Converted OSA values (conversion factor = 2) from stored plasma samples are shown (white circles with gray dashed lines). The timing of surgery (black triangles) and the administration of rVIII-SingleChain (gray triangles) are also shown, with the rVIII-SingleChain dose indicated in units. CSA: chromogenic substrate assay; FVIII: factor VIII; OSA: one-stage clotting assay; rVIII: recombinant factor VIII.

**Table 1.** Coagulation Factor Activity in Stored Plasma From Cases 1, 3 and 4
Time from first rVIII-SingleChain dose (h)	rVIII-SingleChain dose (units)	CSA activity (%)	OSA activity (%)	Converted OSA activity (%)^a	CSA to OSA ratio^b
^aCoagulation activity from OSA × conversion factor of 2. ^bRatio between CSA activity/OSA activity values. CSA: chromogenic substrate assay; OSA: one-stage clotting assay; rVIII: recombinant factor VIII.
Case 1
-3.7		6.5	13.5	27.0	0.48
0.0	3,000
Surgery (thoracoscopic surgery for primary lung cancer (partial lung resection))
7.5		103.1	60.7	121.4	1.70
9.6		97.0	58.5	117	1.66
11.7	2,000
23.9		117.4	70.6	141.2	1.66
24.7	2,000
48.7	2,000	55.4	43.7	87.4	1.27
72.7	2,000	72.1	58.5	117	1.23
96.7	2,000
Case 3
-0.9		5.8	7.5	15.0	0.77
0.0	3,000
Surgery (colonic submucosal dissection)
3.3		67.1	38.9	77.8	1.72
8.0	1,000
19.0		58.9	36.0	72.0	1.64
20.0	2,000
43.9		72.9	44.1	88.2	1.65
44.0	2,000
Case 4
0.0	1,000
3.8		58.9	47.8	95.6	1.23
Surgery (endoscopic mucosal resection for early-stage duodenal tumor)
9.0	1,000
9.2		61.5	52.0	104.0	1.18
21.0	1,000
21.1		90.6	68.7	137.4	1.32
68.4		56.6	51.5	103.0	1.10

Table 1. Coagulation Factor Activity in Stored Plasma From Cases 1, 3 and 4

Time from first rVIII-SingleChain dose (h)

rVIII-SingleChain dose (units)

CSA activity (%)

OSA activity (%)

Converted OSA activity (%)^a

CSA to OSA ratio^b

^aCoagulation activity from OSA × conversion factor of 2. ^bRatio between CSA activity/OSA activity values. CSA: chromogenic substrate assay; OSA: one-stage clotting assay; rVIII: recombinant factor VIII.

Case 1

-3.7

6.5

13.5

27.0

0.48

0.0

3,000

Surgery (thoracoscopic surgery for primary lung cancer (partial lung resection))

7.5

103.1

60.7

121.4

1.70

9.6

97.0

58.5

117

1.66

11.7

2,000

23.9

117.4

70.6

141.2

1.66

24.7

2,000

48.7

2,000

55.4

43.7

87.4

1.27

72.7

2,000

72.1

58.5

117

1.23

96.7

2,000

Case 3

-0.9

5.8

7.5

15.0

0.77

0.0

3,000

Surgery (colonic submucosal dissection)

3.3

67.1

38.9

77.8

1.72

8.0

1,000

19.0

58.9

36.0

72.0

1.64

20.0

2,000

43.9

72.9

44.1

88.2

1.65

44.0

2,000

Case 4

0.0

1,000

3.8

58.9

47.8

95.6

1.23

Surgery (endoscopic mucosal resection for early-stage duodenal tumor)

9.0

1,000

9.2

61.5

52.0

104.0

1.18

21.0

1,000

21.1

90.6

68.7

137.4

1.32

68.4

56.6

51.5

103.0

1.10

**Table 2.** Summary of Cases 1, 2, 3 and 4
	Case 1^a	Case 2^a	Case 3	Case 4
^aThese cases involve the same individual. ^b1 hour post-dose. ^cDays 1, 2, 3 and 5, respectively. ^d2.5 hours post-dose. ^eDays 3 and 5, respectively. ^f“Immediately” before surgery. ^gDays 1 and 2. ^h1.5 hours post-dose. ⁱAfter surgery and on days 1 and 3, respectively. N/R: not reported; OSA: one-stage clotting assay.
Patient characteristics
Age, years	70	71	66	77
Gender	Male	Male	Male	Male
Hemophilia type	Mild hemophilia A without inhibitor	Mild hemophilia A without inhibitor	Mild hemophilia A without inhibitor	Mild hemophilia A without inhibitor
Surgery	Thoracoscopic surgery	Transcatheter arterial chemoembolization for hepatocellular carcinoma	Colonic submucosal dissection	Endoscopic mucosal resection for early-stage duodenal tumor
Real-time coagulation factor activity (measured using OSA), %
Prior to surgery	15	45	10	44
Post-first dose	65^b	67^d	46^f	63^h
Post-operatively	75, 71, 69, 65^c	75, 32^e	47^g	53, 69, 59ⁱ
Dose of rVIII-SingleChain, units
Pre-operative	3,000	2,000	3,000	1,000
Immediately post-operatively	2,000	N/R	1,000	1,000
Post-operatively	2,000 on days 1-4	2,000 on days 1, 2 and 6	2,000 on days 1 and 2	1,000 on day 1
Bleeding
During surgery	2 mL	0 mL	No significant bleeding reported	No significant bleeding reported
Post-operatively	Not observed	Not observed	Not observed	Not observed

Table 2. Summary of Cases 1, 2, 3 and 4

Case 1^a

Case 2^a

Case 3

Case 4

^aThese cases involve the same individual. ^b1 hour post-dose. ^cDays 1, 2, 3 and 5, respectively. ^d2.5 hours post-dose. ^eDays 3 and 5, respectively. ^f“Immediately” before surgery. ^gDays 1 and 2. ^h1.5 hours post-dose. ⁱAfter surgery and on days 1 and 3, respectively. N/R: not reported; OSA: one-stage clotting assay.

Patient characteristics

Age, years

Gender

Male

Hemophilia type

Mild hemophilia A without inhibitor

Surgery

Thoracoscopic surgery

Transcatheter arterial chemoembolization for hepatocellular carcinoma

Colonic submucosal dissection

Endoscopic mucosal resection for early-stage duodenal tumor

Real-time coagulation factor activity (measured using OSA), %

Prior to surgery

Post-first dose

65^b

67^d

46^f

63^h

Post-operatively

75, 71, 69, 65^c

75, 32^e

47^g

53, 69, 59ⁱ

Dose of rVIII-SingleChain, units

Pre-operative

3,000

2,000

3,000

1,000

Immediately post-operatively

2,000

N/R

1,000

Post-operatively

2,000 on days 1-4

2,000 on days 1, 2 and 6

2,000 on days 1 and 2

1,000 on day 1

Bleeding

During surgery

2 mL

0 mL

No significant bleeding reported

Post-operatively

Not observed