J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

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

Journal website http://www.thejh.org

Case Report

Volume 5, Number 2, June 2016, pages 60-66

Should the Dose of Recombinant Activated Factor VII Be Adjusted for Morbidly Obese Patients? Balancing Risk of Bleeding With Thrombosis

Figure 1. Coagulation parameters in relation to factor dosing. The graphic illustrates the coagulation parameters for this case in relation to the dose of FEIBA and rFVIIa. Notably, the partial thromboplastin time (PTT) remains elevated, but the prothrombin time (PT) specimens were < 10 s, suggesting the consistent presence of rFVIIa throughout the ICU stay [4]. The hematocrit remains stable and transfusion needs included 1 unit of packed red blood cells on postoperative day 3. The red line at 23 h designates the change in rFVIIa dose from 15 to 9 mg.

Figure 2. Simulation illustrating dosing (mg) with varying BMI using blood volume, IBW, adjusted body weight with CF, and actual weight. The graphic illustrates the significant variability in dose depending on the weight used to calculate the rFVIIa dose. The values were calculated based on a theoretical case: female of 66 inches in height with increasing weight as noted with BMI values ranging from 25 to 63 kg/m². Weight increase for each increment was 10 pounds. The graph highlights the substantial difference between using the actual body weight and ideal body weight (IBW). Because blood volume increases with increasing BMI, IBW may result in underdosing a morbidly obese patient. Using an estimation of blood volume to calculate the rFVIIa dose still results in a significant difference compared to actual body weight; however, the dose increases gradually with increasing weight, as does the blood volume. Adjusted body weight was included in the graphic, but it should be noted that the correction factor was calculated based on the percent change in blood volume. *Correction factor.

**Table 1.** Calculations of rFVIIa Dosage Based on Pertinent Weight Values
Method of calculation	Equation	Estimated dose rFVIIa	Comment
CF: standard pharmacy correction factor; SQRT: square root.
Body mass index (BMI)	kg/m² 167 kg weight, 167 cm height BMI = 61 kg/m²		Considered extreme obesity by NIH guidelines
Actual body weight	167 kg	90 μg/kg × 167 kg Dose = 15,030 μg	Dose assumes blood volume increases proportionately with actual body weight
Ideal body weight (IBW)	Females = 45.5 kg + (2.3 kg × every inch > 60) IBW = 57 kg	90 μg/kg × 57 kg Dose = 5,130 μg	Assumes no increase in blood volume with increase adipose
Dose based on blood volume [5]	= 70 mL/kg/(SQRT (patient BMI (kg/m²)/22) Explanation of variables within equation: Indexed blood volume healthy adults = 70 mL/kg BMI for patient divided by 22 accounts for deviation from IBW	= 70/(SQRT (61/22) = 70/1.665 = 42 mL/kg Standard blood volume estimate by actual weight: = 70 mL/kg × 167 kg = 11,690 mL Indexed blood volume by actual weight: = 42 mL/kg × 167 kg = 7,014 mL Solve for “x” using ratio for indexed dose: (x/7,014 mL) = (15 mg/11,690 mL) x = (15 mg × 7,014 mL)/11,690 mL = 9 mg ( 9,000 μg)	The blood volume corrected for increasing BMI by Lemmens et al [5] formula is 40% lower than the uncorrected empiric estimate of 70 mL/kg used for non-obese adults. This line of reasoning assumes that plasma volume change is equal to blood volume change.
Adjusted body weight	IBW + (CF (Actual Body Weight - IBW)) 57 + (0.4 (167 - 57)) 57 + 44 = 101 kg	90 μg/kg × 101 kg Dose = 9,090 μg	Adjusted body weight with a correction factor of 0.4 compares closely with change in blood volume estimation by Lemmens et al [5]

Table 1. Calculations of rFVIIa Dosage Based on Pertinent Weight Values

Method of calculation

Equation

Estimated dose rFVIIa

Comment

CF: standard pharmacy correction factor; SQRT: square root.

Body mass index (BMI)

kg/m²
167 kg weight, 167 cm height
BMI = 61 kg/m²

Considered extreme obesity by NIH guidelines

Actual body weight

167 kg

90 μg/kg × 167 kg
Dose = 15,030 μg

Dose assumes blood volume increases proportionately with actual body weight

Ideal body weight (IBW)

Females = 45.5 kg + (2.3 kg × every inch > 60)
IBW = 57 kg

90 μg/kg × 57 kg
Dose = 5,130 μg

Assumes no increase in blood volume with increase adipose

Dose based on blood volume [5]

= 70 mL/kg/(SQRT (patient BMI (kg/m²)/22)
Explanation of variables within equation:
Indexed blood volume healthy adults = 70 mL/kg
BMI for patient divided by 22 accounts for deviation from IBW

= 70/(SQRT (61/22) = 70/1.665 = 42 mL/kg
Standard blood volume estimate by actual weight:
= 70 mL/kg × 167 kg = 11,690 mL
Indexed blood volume by actual weight:
= 42 mL/kg × 167 kg = 7,014 mL
Solve for “x” using ratio for indexed dose:
(x/7,014 mL) = (15 mg/11,690 mL)
x = (15 mg × 7,014 mL)/11,690 mL = 9 mg ( 9,000 μg)

The blood volume corrected for increasing BMI by Lemmens et al [5] formula is 40% lower than the uncorrected empiric estimate of 70 mL/kg used for non-obese adults.
This line of reasoning assumes that plasma volume change is equal to blood volume change.

Adjusted body weight

IBW + (CF (Actual Body Weight - IBW))
57 + (0.4 (167 - 57))
57 + 44 = 101 kg

90 μg/kg × 101 kg
Dose = 9,090 μg

Adjusted body weight with a correction factor of 0.4 compares closely with change in blood volume estimation by Lemmens et al [5]

**Table 2.** ROTEM With Highlighted Bolded Cells Designating Abnormal Values
Hours from SICU admit	Place	rFVIIa dose	Extem measures	Intem measures
CFT: clot formation times; CT: clotting time; MCF: maximum clot firmness.
-5.1	OR	15 mg	49	57	69	118	97	60	8	13			1,420
-0.5	OR	52	60	73	107	46	62	56	63	62	158	395	65
-0.4	OR	57	64	76	88	45	66	8	14	9	1,822	1,250	26
1.5	SICU	49	57	70	115	49	60	60	61	53	61	166
6.7	SICU	51	59	67	115	72	61	54	61	60	189	526	61
10.4	SICU	54	62	71	101	54	63	37	56	42	341	683	64
25.2	SICU	9 mg	51	60	78	105	48		35		40	356	579
29.7	SICU	50	58	76	97	45	61	23	36	29	504	790
35.9	SICU	49	58	76	105	41	61	16	25	24	837	842	36
42.8	SICU	58	66	78	87	58	69	19	35	25	624	904	52
47.5	SICU	58	65	75	92	48	68	24	40	35	487	836
64.3	SICU	55	62	75	82	50	64					768
93.5	SICU	59	65	77	72	71	68	19	33	25	635	793
115.0	SICU	57	64	74	74	64	67	18	27	38	682	1,057	40
161.3	SICU	63	68	79	63	52	69	29	43	36	382	642

Table 2. ROTEM With Highlighted Bolded Cells Designating Abnormal Values

Hours from SICU admit

Place

rFVIIa dose

Extem measures

Intem measures

A 10

A 20

Alpha angle

CFT

MCF

A 10

A 20

Alpha angle

CFT

MCF

No range

50 - 70

65-80°

48 - 127 s

43 - 82 s

50 - 70 mm

No range

51 - 72

70-81°

45 - 110 s

122 - 208 s

51 - 72 mm

CFT: clot formation times; CT: clotting time; MCF: maximum clot firmness.

-5.1

15 mg

118

1,420

-0.5

107

158

395

-0.4

1,822

1,250

1.5

SICU

115

166

6.7

SICU

115

189

526

10.4

SICU

101

341

683

25.2

SICU

9 mg

105

356

579

29.7

SICU

504

790

35.9

SICU

105

837

842

42.8

SICU

624

904

47.5

SICU

487

836

64.3

SICU

768

93.5

SICU

635

793

115.0

SICU

682

1,057

161.3

SICU

382

642