Outcomes of Patients Who Undergo Transfusion of Fresh Frozen Plasma: A Prospective, Observational, Multicentre Cohort Study in Hiroshima, Japan

Figures & data

Table 1 Guidelines for FFP Transfusion Established by Ministry of Health, Labour and Welfare of Japan (2017)

Trigger values of coagulation tests (as reference)	<PT>	(i) INR 2.0 or higher, or (ii) 30% or lower
	<APTT>	Above twice the upper limit of the standard value at each medical institution
	<Fibrinogen>	150 mg/dL or less, or when there is a risk of further deterioration
Indications for FFP	1) Coagulation factor supplementation
		a) Complex coagulopathy	i. Liver disease with bleeding tendency
			ii. L-asparaginase administration related
			ii. Disseminated intravascular coagulation (DIC)
			iv. Dilutional coagulopathy caused by massive transfusion and fluid infusion
		b) Coagulation factor replacement in the absence of concentrated product (when bleeding or before invasive procedures)
		c) Correction of warfarin effect
	2) Plasma exchange (thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome)
Inappropriate indications	1. Expansion of circulatory volume
	2. For nutritional purposes
	3. For promotion of wound healing
	4. Administration to terminal patients
	5. Prophylactic transfusion  ✓ In case of surgery or trauma that does not require a large amount of blood transfusion  ✓ Chronic liver disease  ✓ Severe burns  ✓ Acute pancreatitis

Abbreviations: FFP, fresh frozen plasma; PT, prothrombin time; INR, international normalised ratio; APTT, activated partial thromboplastin time.

Figure 1 Age distribution of patients who underwent FFP transfusion.

Figure 2 Distribution of indications for FFP transfusion, and underlying disease in which the reason for FFP use was ”inappropriate”.

Table 2 Coagulation Test Values Before and After FFP Transfusion by Patients’ Outcomes at Day 28

		N	Before FFP Transfusion	After FFP Transfusion	P*
PT-INR	Total	1051	1.3 (0.1–14.6)	1.2 (0.2–23.9)	<0.0001
	Alive	826	1.3 (0.1–14.1)	1.2 (0.2–23.9)	<0.0001
	Dead	151	1.6 (0.9–14.6)	1.5 (0.9–5.6)	0.1954
APTT	Total	947	36.1 (7.8–321)	34.7 (1.2–378)	<0.0001
	Alive	746	34.9 (7.8–200)	33.5 (1.2–378)	<0.0001
	Dead	132	51.2 (24.5–321)	44.2 (9.9–250)	0.1891
Fib	Total	654	206.6 (1–965)	236.9 (1.2–1023)	<0.0001
	Alive	541	213.7 (1–965)	246 (1.2–901)	<0.0001
	Dead	94	173.4 (25–796)	184.9 (41–1023)	0.6863

Notes: Data are shown as median (min-max). *Paired t-test between before and after FFP transfusion.

Abbreviations: FFP, fresh frozen plasma; SD, standard deviation; PT-INR, prothrombin time–international normalised ratio; APTT, activated partial thromboplastin time; Fib, fibrinogen.

Table 3 Univariate and Multivariate Analysis on Factors Associated with the Outcome at Day 28 After FFP Transfusion

	Outcome at 28 Days		Univariable Analysis*		Multivariable Analysis#
	Dead N (%)	Alive N (%)	OR [95% CI]	p-value	AOR [95% CI]	p-value
Age (years)
≤39	12(10.2)	106(89.8)	1		1
40–64	48(17.1)	233(82.9)	1.8[0.9–3.6]	0.2337	1.7 [0.5–5.7]	0.4151
65–74	50(15.8)	266(84.2)	1.7[0.9–3.2]	0.4029	3.5 [1.0–11.9]	0.0463
Over 75	89(20.3)	349(79.7)	2.3[1.2–4.3]	0.0333	3.4 [1.0–11.0]	0.0452
Sex
Female	66(15.2)	368(84.8)	0.8[0.6–1.1]	0.1520	1.2 [0.7–2.0]	0.5223
Male	133(18.5)	586(81.5)	1		1
Perioperative use of FFP
No	128(31.9)	273(68.1)	4.8[3.4–6.6]	<0.0001	4.6 [2.6–8.2]	<0.0001
Yes	66(9.0)	671(91.0)	1		1
Indication for FFP
Coagulopathy caused by liver disease	50(33.6)	99(66.4)	6.5[3.9–10.7]	<0.0001	2.7[1.2–6.2]	0.0190
Coagulopathy associated with DIC	48(33.1)	97(66.9)	6.4[3.8–10.5]	<0.0001	2.1[0.9–5.2]	0.0922
Dilutional coagulopathy	59(15.7)	316(84.3)	2.4[1.5–3.8]	<0.0001	1.4[0.6–2.9]	0.4094
Coagulation factor replacement	6(17.1)	29(82.9)	2.7[1.0–6.9]	0.0368	1.3[0.2–7.2]	0.7691
Warfarin effects correction	6(30.0)	14(70.0)	5.5[2.0–15.4]	0.0003	5.8[1.0–32.3]	0.0613
Inappropriate use	31(7.2)	399(92.8)	1		1
Pre-dose PT-INR
≥2	59(35.1)	109(64.9)	3.2[2.2–4.6]	<0.0001	-
<2	130(14.6)	761(85.4)	1
Pre-dose APTT(seconds)
≥75	49(48.0)	53(52.0)	5.6[3.7–8.7]	<0.0001	1.5[0.7–3.2]	0.2760
<75	127(14.1)	775(85.9)	1		1
Pre-dose Fibrinogen (mg/dl)
≤150	61(26.8)	167(72.3)	2.2[1.5–3.2]	<0.0001
>150	78(14.3)	468(85.7)	1
Amount of transfused FFP (Units)
≥7	127(22.8)	431(77.2)	2.1[1.5–2.9]	<0.0001	2.4[1.1–4.9]	0.0175
<7	73(12.3)	523(87.8)	1		1
Amount of transfused RBC (Units)
≥7	92(20.7)	352(79.3)	1.5[1.1–2.1]	0.0090	1.4[0.7–2.9]	0.3116
<7	102(14.7)	590(85.3)	1		1
Ratio FFP/RBC
>1.5	59(23.5)	192(76.5)	1.8[1.2–2.6]	0.0017	1.2[0.6–2.3]	0.6373
≤1.5	99(14.8)	572(85.3)	1		1
Post-dose PT-INR
≥2	44(58.5)	30(40.5)	11.7[7.0–19.4]	<0.0001	12.8[4.8–34.1]	<0.0001
<2	104(11.2)	829(88.9)	1		1
Post-dose APTT (seconds)
≥75	27(57.5)	20(42.3)	9.6[5.2–17.7]	<0.0001	9.5[3.1–29.0]	<0.0001
<75	109(12.3)	776(87.7)	1		1
Post-dose Fibrinogen (mg/dl)
≤150	41(36.0)	73(64.0)	4.3[2.7–6.8]	<0.0001
>150	74(11.6)	566(88.4)	1
Total number of days of FFP administration (days)
≥3	52(29.9)	122(70.1)	2.4[1.7–3.5]	<0.0001
<2	147(15.1)	828(84.9)	1

Notes: Excluding the cases of plasma exchange (N=34), factors associated with the mortality outcome at 28 days after FFP transfusion were analysed. *Chi-square test with post-hoc multiple comparisons by Bonferroni correction were used to compare groups. ^#Logistic regression analysis with the stepwise method: sex, age, and the amount of transfused FFP were forced entry predictors, and the other 11 variables were selected using the stepwise method (p<0.25). R² = 0.3084, model p-value < 0.0001, n = 1265.

Abbreviations: OR, odds ratio; AOR, adjusted odds ratio; CI, confidence interval; FFP, fresh frozen plasma; DIC, disseminated intravascular coagulation; APTT, activated partial thromboplastin time; PT-INR, prothrombin time and international normalized ratio; RBC, red blood cells.