14例恶性抗磷脂综合征病例报道及临床分析

doi:10.19723/j.issn.1671-167X.2018.06.016

摘要/Abstract

摘要：

目的: 恶性抗磷脂综合征(catastrophic antiphospholipid syndrome, CAPS),即Asherson综合征,是一种以累及多系统、脏器、组织的多发血管内血栓,高滴度的抗磷脂抗体和高死亡率为特征的一种抗磷脂综合征(antiphospholipid syndrome, APS)亚型。本文分析CAPS的临床表现、实验室检查及治疗,以增加对该病的认识及诊治水平。方法: 回顾性分析APS上海数据库的14例CAPS患者的临床资料并进行描述性统计分析。结果: 14例患者中12例符合2003年第10届抗磷脂抗体国际会议中通过的CAPS分类标准中的确诊APS,2例符合APS可能,其中原发性APS有3例,11例继发于系统性红斑狼疮(systemic lupus erythematosus,SLE)。感染是最常见的发病诱因,其次是狼疮活动和外科手术。临床事件中,动脉血栓最好发的部位为脑和肺,静脉血栓最常见于四肢静脉。抗心磷脂抗体(anticardiolipin antibody, aCL)、抗β2糖蛋白1抗体(anti-β2 glyeoprotein Ⅰ antibody, aβ2GPI)、狼疮抗凝物(lupus anticoagulant, LA)均阳性的患者占54.55%,血小板减少和血红蛋白降低发生于大部分的CAPS患者,其中大多证实为溶血性贫血。死亡病例6例,抗凝药物、激素、静脉注射丙种球蛋白和/或血浆置换的三联疗法可以改善患者的预后,合并SLE和微血管病性溶血性贫血的患者分别可以使用环磷酰胺和利妥昔单抗。结论: CAPS是急性发生的以大量微血栓形成及高抗磷脂抗体滴度为特点的危重症,可以导致多脏器功能衰竭,因本病预后差,及时的诊断和积极的治疗是改善预后的关键。

关键词: 抗磷脂抗体, 恶性抗磷脂综合征, 血栓栓塞

Abstract:

Objective: Catastrophic antiphospholipid syndrome (CAPS), also known as Asherson’s syndrome, is a special subtype of antiphospholipid syndrome (APS) characterized by multiple intravascular thrombosis involving multiple organs systems or tissues simultaneously or continuously, high titer antiphospholipid antibodies and high mortality rate. This article’s aims was to analyze the clinical manifestation, laboratory examination and treatment therapy of CAPS for the purpose of improving the understanding, diagnosis and treatment of the disease in clinical practice.Methods:Retrospective analysis and descriptive statistics were applied to the clinical manifestations and laboratory findings of 14 CAPS cases from APS Shanghai Database (APS-SH) with catastrophic antiphospholipid.Results:Of the 14 CAPS patients, 12 cases satisfied the 2003 CAPS Classification Criteria accepted in the 10 ^th International Congress on Antiphospholipid Antibody, and were diagnosed as definite APS and 2 cases were diagnosed as probable CAPS. Three cases were categorized as primary APS and 11 as APS secondary to systemic lupus erythematosus (SLE). Infection was mostly commonly seen before the onset of CAPS, followed by SLE activity and surgery. Among the involved organs, systems and tissues, brain and lung were most commonly affected sites of arterial thrombosis while peripheral vein was most commonly affected in venous thrombosis events among the clinical events. Triple positivity of anticardiolipin antibody (aCL), anti-β2 glyeoprotein Ⅰ antibody (aβ2GPI), lupus anticoagulant (LA) were detected in 54.55% of the patients. Thrombocytopenia and decreased hemoglobin were frequently seen in the CAPS patients, and the majority proved to be hemolytic anemia. Of all the cases, 6 ended with death. The triple therapy strategy (anticoagulants, glucocorticoid, intravenous immunoglobulin and/or plasma exchange) could help to improve prognosis, cyclophosphamide and rituximab might benefit the patients with other comorbidities such as SLE and micro-angiopathic hemolytic anemia (MHA). Conclusion:CAPS patients suffer from life-threatening acute multiple small vessel thrombosis with high titer of antiphospholipid antibody, potentially leading to multiple organ failure and a poor prognosis, thus early diagnosis and sufficient treatment are critical to prevent the progression of disease and improve the prognosis.

Key words: Antiphospholipid antibodies, Catastrophic antiphospholipid syndrome, Thromboembolism

中图分类号:

R593.2

顾婕昱,陆翠,石慧,杨程德. 14例恶性抗磷脂综合征病例报道及临床分析[J]. 北京大学学报（医学版）, 2018, 50(6): 1033-1038.

Jie-yu GU,Cui LU,Hui SHI,Cheng-de YANG. Case series and clinical analysis of 14 cases of catastrophic antiphospholipid syndrome[J]. Journal of Peking University(Health Sciences), 2018, 50(6): 1033-1038.

图/表 3

表1

14例CAPS患者临床资料"

Patient No.	Gender	Age/ years	Positive numbers of aCL/aβ2 GPI/LA	Major diagnosis	Sites of arterial thrombosis	Sites of venous thrombosis	Other involved organs	Final diagnosis
1^bc#	Male	50	3	PAPS	Brain,superficial femoral artery, coronary artery	Bilateral lower limb	VHD, PAH, livedo reticularis, skin ulcers, renal insufficiency	CAPS
2^bc#	Female	44	3	SLE, SAPS	Brain, right toe	Eye, kidney	Skin ulcers, renal insufficiency	CAPS
3^bc#	Female	54	1	SLE, SAPS	Brain	Left popliteal vein	VHD, PAH, skin ulcers	CAPS
$4 b *#$	Female	14	1	SLE, SAPS	Brain, left lower limb		VHD, livedo reticularis	CAPS
$5 abc *#$	Male	16	2	SLE, SAPS	Kidney, superior mesenteric artery	Left femoral vein	VHD, renal insufficiency	CAPS
6^c	Female	56	1	SLE, SAPS	Spleen	Left lower limb, kidney	Renal insufficiency	CAPS
7^c	Female	45	1	SLE, SAPS	Brain, coronary artery		VHD	CAPS
$8 b *$	Female	32	2	SLE, SAPS	Brain, spleen	Upper limb, cerebral sinus	Renal insufficiency	CAPS
9^b	Female	29	3	SLE, SAPS, AIH	Brain	Venae cava inferior	VHD, PAH	Probable CAPS
10^abc#	Female	18	3	SLE, Latent syphilis	Brain, coronary artery, lung		VHD, PAH, myocardial fibrosis, pneumorrhagia, renal insufficiency	CAPS
11^a	Male	24	3	PAPS	Brain (right middle cerebral artery), lung	Axillary vein, branchial vein, bilateral cavernous sinus of internal jugular vein		CAPS
12^b	Male	56	3	SLE, SAPS	Aortaabdominalis, superior mesenteric artery, brain	Skin	VHD, PAH	CAPS
13	Male	20	1	PAPS	Lung, spleen	Venae cava inferior		CAPS
14^b	Female	50	1	SLE, SAPS	Brain, lung		VHD, PAH	Probable CAPS

表1

表2

表3

参考文献 12

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Clinical manifestation	n (%)
Arterial thrombosis	14 (100.00)
Brain	11 (78.57)
Lung	4 (28.57)
Coronary artery	3 (21.43)
Spleen	3 (21.43)
Peripheral artery	3 (21.43)
Superior mesenteric artery	2 (14.29)
Kidney	1 (7.14)
Venous thrombosis	10 (71.43)
Peripheral vein	6 (42.86)
Cerebral venous sinuses	2 (14.29)
Kidney	2 (14.29)
Venae cava inferior	2 (14.29)
Central vein of eye	1 (7.14)
Skin	1 (7.14)
Pregnancy morbidity^a	3 (42.86)
Valvular heart disease	9 (64.29)
Pulmonary artery hypertension	6 (42.86)
Renal insufficiency	6 (42.86)
Livedo reticularis	2 (14.29)
Laboratory findings
Thrombocytopenia	10 (71.43)
Leukocytopenia	2 (28.57)
Decreased hemoglobin	12 (85.71)
Positive lupus anticoagulant	8 (72.73)
Positive anti-cardiolipin	11 (78.57)
Positive anti-β2GPI	9 (64.29)
Positive anti-nuclear antibody	11 (78.57)
Positive extractable nuclear antigen	4 (28.57)
Elevated ESR	8 (72.73)

Treatment	n (%)
Individual treatments
AC^a	14 (100.00)
CS	12 (85.71)
IVIG	11 (78.57)
CTX	4 (28.57)
PE	3 (21.43)
RTX	1 (7.14)
FK506	1 (7.14)
Combined treatments
AC+CS+IVIG	7 (50.00)
AC alone	2 (14.28)
AC+CS+CTX	1 (7.14)
AC+CS+PE+CTX	1 (7.14)
AC+CS+IVIG+CTX	1 (7.14)
AC+CS+IVIG+PE+FK506	1 (7.14)
AC+CS+IVIG+PE+CTX	1 (7.14)