Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency

Figures & data

Table 1 Treatment reports of substitution with human protein C concentrates inpatients with severe protein C deficiency

Reference #	Patient age	Clinical presentation	Dose of protein C concentrate*		Concomitant treatment	Outcome
			Acute therapy	Prophylactic therapy
^Citation40	3 newborns	Intracranial hemorrhage, PF, eye involvement	60–80 IU/kg i.v. 6–8 h	108 IU/kg/d 306 U/kg/d s.c. over 1–12 h		No recurrence
^Citation41	newborn			550 IU/d, then 85 IU/kg i.v. 3x per wk	LMWH	No recurrence
	1 day	PF, intracranial hemorrhage, eye involvement	156 U/kg 12 h	90 IU/kg i.v. 3x per wk		Blind, developmental delay
^Citation42	5 (4 < 5 wk, 12 y)	PF, necrotic hematoma, DVT, surgery	Protexel^® 125 ± 49 IU/kg/d i.v. (median 105 IU/kg/d)	Protexel^® 24–90 U/kg/d i.v.	UFH, LMWH, OAC	Resolution, successful surgery
^Citation43	34 wk of gestation	PF, intracranial hemorrhage, infarction	80 IU/kg/d i.v.		UFH	No recurrence
^Citation44	22 y	Cesarian section		3000 IU i.v. once	LMWH	Successful
^Citation45	29 d	PF, eye involvement	80 U/kg i.v. 12 h	350 U/kg s.c. 48 h (pump), 192 U/kg/48 h	FFP	No recurrence, visual impairment
^Citation35	2 d	PF	125 U/kg/d i.v. and s.c.		LMWH	Resolution
		Recurrent PF on OAC		75–66 IU/kg/d s.c.		No recurrence
^Citation46	21 d	PF; eye involvement	50 U/kg i.v. 8 h, then 200 U/kg 12 h	250–350 U/kg s.c. 2 d	FFP + LMWH for 21 d	No recurrence, blind
	10 d	Periventricular infarction, eye involvement	50–100 U/kg i.v. 8 h	2000U s.c. 2 d		No recurrence, blind
^Citation47	15 d	PF	100–200 IU/kg i.v. 6–8 h		FFP 10–15 mL/kg	Blind, neurological deficits
		Intracranial hemorrhage	200 IU/kg i.v. 12 h for 3 days		every 12 h for 6 d
		Initiation of OAC		200 IU/kg 12 h for 5 wk	OAC
		Shunt revision		200 IU/kg 12 h for 3 d
^Citation48	4 y	Initiation of OAC	63 IU/kg 12 h		OAC	Successful
^Citation17	8 y	Coumarin-induced skin necrosis	40 IU/kg/d for 8 d		OAC	No recurrence
^Citation49	7 mo	PF		500 IU/wk i.v.	OAC	No recurrence
^Citation50, ^Citation51	10 mo	Ventriculo-peritoneal shunt and vitrectomy		50 IU/kg i.v. every 12–48 h	LMWH	Successful surgery
	32 y	Thrombophlebitic episode Varikosectomy	50 IU/kg once, 40 IU/kg 24 h	40 IU/kg, then 15–20 IU/kg/d for 8 d	LMWH	Resolution, successful surgery
^Citation52	2 d	PF, eye involvement recurrent PF	Dose n.a. i.v. for 6 wk 100–125 IU/kg s.c., then 75 IU/kg/d 3–5 d	75 IU/kg/d s.c. (500 U/ml)	LMWH	Blind
^Citation53	25 mo	PF	Dose n.a.		FFP 5 mL/kg/d	No recurrence
^Citation54	36 wk of gestation	Intracranial hemorrhage, eye involvement	80 IU/kg i.v.			Resolution of macular hemorrhage, hydrocephalus
^Citation33	Newborn	Bilateral renal vein thrombosis	Dose n.a.	Dose n.a. 12 h	UFH, LMWH	Renal insufficiency
^Citation18	16 y	Coumarin-induced necrosis	80U/kg i.v.	80 IU/kg/d for 5 d	UFH, LMWH OAC	Resolution
^Citation55	4 y	PF	200 IU/kg i.v. 6 h for 2 days		LMWH OAC	Resolution
^Citation56	9 d	PF, cerebral infarction, eye involvement	20 IU/kg i.v. 6 h to 80 IU/kg i.v. 12 h	80 IU/kg i.v. 12 h to 2x per wk, 350 U/kg s.c. 48 h	OAC	Blind, hemiparesis
^Citation57	4 newborns	PF, cerebral infarction, eye involvement	Dose n.a. i.v.	250 IU/kg s.c. 3 d 100 IU/kg s.c.2x week 100 IU/kg/d s.c. 350 IU/kg 48 h s.c.		No recurrence in all patients
^Citation58	11 d	PF, eye involvement	Dose n.a.	Dose n.a.		Resolution, visual impairment
	9 d	PF/DIC, eye involvement	Dose n.a.		OAC	Resolution, visual impairment
^Citation59	10 d	PF, bilateral renal vein thrombosis	Dose n.a.			Improvement
^Citation19	9 y	DVT, recurrent coumarin-induced skin necrosis	40 IU/kg 18 h to 100 U/kg 24 h for 2 wk		Heparin OAC	Resolution
^Citation60	27 y	pregnancy and cesarean section		50 IU/kg 3x per wk 4th–13th wk and 35th wk to post-partum	OAC	Successful pregnancy and delivery
^Citation61	2.5 y	recurrent skin necrosis on OAC	100–200 IU i.v. 6 h	250 U/kg s.c. 3 d over 2 h (pump)		No recurrence
^Citation62	20 d	PF, eye involvement	70 IU/kg i.v. 6 h	500 IU/kg/d i.v.	OAC	Resolution, no recurrence
^Citation23	4 d	PF, eye involvement, surgery; recurrent PF	20 IU/kg i.v., then 40 IU/kg 6h;		OAC	Resolution
	3 mo	Dialysis, difficult ACO		20 IU/kg/d i.v., then 80 IU/kg/d	OAC	Renal failure
	2 d	PF, eye involvement, DIC	50 IU/kg i.v.	50 IU/kg 2x per wk	OAC	Blind
	20 d	PF, eye involvement	40 IU/kg i.v. 8 h	500 IU/d, 110 IU/kg 2x per week	OAC	Blind
	7 d	PF, eye involvement; recurrent PF	40 IU/kg i.v. 8 to 12 h	750 IU/d, then 1000 IU/d, then 3000 IU s.c. 3 d	OAC	Visual impairment
	4 d	PF	40–80 IU/kg i.v. 6 h	500–1000 IU/d		Resolution
	15 d	PF, eye involvement	120 IU/kg i.v. 8–12–24 h	500 IU/d	OAC	Blind
	5 d	PF, eye involvement; recurrent PF	80 IU/kg i.v. 6 h to 125 IU/kg 8 h		OAC	Blind, mild neurological deficits
	6 wk	PF, eye involvement, cerebral hemorrhage	70 IU/kg i.v. 6 h	30 IU/kg/d		Died
^Citation63	2 d	PF	100–200 IU i.v. 6 h	500–1000 IU/d i.v.		Resolution,
	24 h	PF, eye involvement	Dose n.a.	Dose n.a.		Resolution, blind
^Citation20	52 y	DVT, recurrent coumarin-induced skin necrosis	50 IU/kg 12 h i.v.	50 IU/kg 12 h i.v. for 10 days	LMWH warfarin	Resolution, no recurrence
^Citation64	2 d, 28 wk of gestation	PF, eye involvement PF, intracerebral hemorrhage, eye involvement	Dose n.a. i.v. 12 h		heparin <24 h	Blind Deceased at 23 d
^Citation65	2 d	PF, eye involvement	250 IU 6 h		FFP 15 ml/kg every 12 h, OAC	Resolution
^Citation21	58 y, 41 y	Recurrent DVT, recurrent coumarin-induced skin necrosis; Pharmacokinetic studies	80 IU/kg i.v.
^Citation66	17 y	DVT, initiation of OAC	39 IU/kg i.v. 6 h, then 18 h for 4 d		Heparin i.v. 40000 IU/d for 5 d, OAC	Successful switch to OAC
^Citation67	7 y	Pharmacokinetic studies	40 U/kg i.v.		OAC
^Citation14	Newborn	PF	20 to 40 IU/kg 6h i.v., at 14 d 30 IU/kg 12 h			Resolution
		Open heart surgery (VSD)		135 IU/kg i.v. once, 16 IU/kg continuous i.v. during surgery, then 60 IU/kg 6 h for 41 d, then 100 IU/kg/d i.v.		Successful surgery
		Catheter-related thrombosis of VCS		240 IU/kg/d for 3 wk	Heparin i.v. (30–50 IU/kg/h)
^Citation68	10 mo	PF		Human protein C and S concentrate HT (Schwab+Co, Vienna): 100 U/kg PC every 48 h for >7 months		No recurrence

Notes:

* Ceprotin^® by Baxter or former human protein C preparation by Immuno AG; others indicated.

Abbreviations: PF, purpura fulminans; DIC, disseminated intravascular coagulation; DVT, deep vein thrombosis; h, hour(s); d, day(s); wk, week(s); mo, month(s); y, year(s); OAC, oral anticoagulation; FFP, fresh frozen plasma; UFH, unfractionated heparin; LMWH, low-molecular-weight heparin; n.a., not available.

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