Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.
Antithrombin III ; genetics ; Antithrombin III Deficiency ; etiology ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Protein C ; genetics ; metabolism ; Venous Thromboembolism ; complications ; genetics ; Young Adult

OBJECTIVETo observe the relationship between vitamin D status and seasons, disease activity, disease location, growth and steroid treatment in children with Crohn's disease (CD). To search for the risk factors of vitamin D deficiency in CD children. To discuss the role of vitamin D in the pathogenesis and treatments of CD.

METHODSixty CD children (63.3% male) and 121 sex- and age-matched healthy subjects were enrolled. Data including growth, clinical characteristics, time for vitamin D blood test, erythrocyte sedimentation rate, C reactive protein, serum 25(OH)D concentration and steroid treatments were collected. The relationship between vitamin D status and disease activity, disease location, growth and steroid treatments in children with CD were analized.

RESULTThe serum concentration of 25(OH)D was 57.2(22.3-246.0) nmol/L, which was significantly lower than that of controls (67.3 (57.3-78.4) nmol/L) (Z=-5.009, P=0.000). Hypovitaminosis D was most prevalent during the winter and spring (November to April, 46.8(31.8-83.4) nmol/L) rather than summer and autumn (May to October, 63.3(22.3-246.0) nmol/L, Z=-1.994, P=0.046). Univariate logistic regression demonstrated that factors increasing the risk of vitamin D deficiency in Crohn's disease were: age over 10 years (OR=4.571, 95% CI: 1.452-14.389), small intestine involved diseases (OR=5.211, 95% CI: 1.278-21.237), high C reactive protein levels (≥8 mg/L) (OR=4.500, 95% CI: 1.094-18.503) and steroid therapy (OR=4.297, 95% CI: 1.413-13.068). Among those risk factors, all but age were determined to be risks of vitamin D deficiency by further multivariate logistic regression. There was no significant correlation between vitamin D deficiency and gender, disease duration, stricture, penetration, perianal disease (fistula, ulcer or abscess), white blood cell counts, hemoglobin, platelet counts, erythrocyte sedimentation rate, serum albumin levels, pediatric Crohn's disease activity index and nutrition therapy (P>0.05).

CONCLUSIONHypovitaminosis D was prevalent in children with CD. Serum concentration of vitamin D was associated with season. Steroid treatment, small intestine involved disease and high C reactive protein (more than 8 mg/L) are risk factors of vitamin D deficiency in CD children.

C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Crohn Disease ; complications ; Female ; Humans ; Logistic Models ; Male ; Prevalence ; Risk Factors ; Seasons ; Vitamin D ; blood ; Vitamin D Deficiency ; complications ; Vitamins ; blood

OBJECTIVETo study the molecular pathogenesis of protein C (PC) deficiency in a patient with pulmonary embolism and in his family members.

METHODSAnticoagulated blood samples were collected from the proband and his family members to detect PC, PS and AT activities. PC antigen level was measured using ELISA. The genomic DNA was extracted to amplify all the 9 exons and their flanking sequences of PC gene using PCR, and the PCR products were sequenced. The mutated exons identified were amplified and sequenced for the other family members.

RESULTSThe proband and his parents and sister were identified as carriers of PC gene mutation, which led to type II PC deficiency. Sequencing of the proband's PC gene showed two heterozygous point mutations in exon 3 (G5540A) and exon 7 (C10230T) to cause compound heterozygous mutations of PC E29K and PC R147W, which were inherited from his father and mother, respectively. His sister was a heterozygote of PC R147W.

CONCLUSIONThe proband is a compourd heterozygous mutations carrier of PC E29K and PC147W. PC E29K is a novel PC mutation, and PC R147W is a reported PC gene mutation seen in patients with type II hereditary PC deficiency and recurrent thrombosis.

Adolescent ; Base Sequence ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Protein C ; genetics ; Protein C Deficiency ; complications ; genetics ; pathology ; Pulmonary Embolism ; etiology ; genetics

Cerebral Infarction ; etiology ; Enzyme Activation ; Humans ; Infant ; Male ; Protein C Deficiency ; complications ; Protein S Deficiency ; complications

Mesenteric venous thrombosis is a clinically very rare disease, and may cause bowel infarction and gangrene. Difficulty in the dignosis the disease due to its non-specific symptoms and low prevalence can cause a clinically fatal situation. Mesenteric venous thrombosis may be caused by both congenital and acquired factors, and protein C deficiency, which is a very rare genetic disorder, is one of many causes of mesenteric thrombosis. The authors experienced a case of mesenteric venous thrombosis caused by protein C deficiency in a patient with duodenal ulcer bleeding, so here we report a case together with literature review.
Duodenal Ulcer/*complications/diagnosis ; Endoscopy, Gastrointestinal ; Humans ; Male ; *Mesenteric Veins ; Middle Aged ; Peptic Ulcer Hemorrhage/*complications ; Protein C Deficiency/*complications/diagnosis ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/etiology/ultrasonography

Portal vein thrombosis (PVT) is an uncommon cause of presinusoidal portal hypertension. Among various hepatoportal disorders, noncirrhotic portal hypertension conditions such as idiopathic portal hypertension (IPH) are considered to have a close relation with PVT. PVT is known to have several predisposing conditions, including infection, malignancies, and coagulation disorders. There is growing interest and recognition that deficiencies in proteins C and S are associated with a hypercoagulable state. These deficiencies are regarded as key factors of systemic hypercoagulability and recurrent venous thromboembolism. We report the case of a 19-year-old male diagnosed as IPH with PVT and combined deficiencies in proteins C and S.
Humans ; Hypertension, Portal/complications/*diagnosis/pathology ; Male ; *Portal Vein ; Protein C Deficiency/*complications ; Protein S Deficiency/*complications ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/*diagnosis/pathology ; Young Adult

Protein C is an important physiological anticoagulant factor. Protein C deficiency has been linked to venous thrombosis at unusual sites, including the cerebral and mesenteric veins. Hereditary protein C deficiency is inherited primarily as an autosomal dominant trait with incomplete penetrance. Protein C and S deficiencies are known to increase the risk of venous thrombosis and pulmonary thromboembolism. Testing for protein C levels and function is necessary for the detection of both type I and type II protein C deficiency. In this article, we report a case of pulmonary embolism and mesentery ischemia due to type 1 protein C deficiency.
Colonoscopy ; Humans ; Ischemia/*diagnosis/etiology ; Magnetic Resonance Angiography ; Male ; Mesenteric Veins ; Middle Aged ; Protein C Deficiency/*complications/genetics ; Pulmonary Embolism/*diagnosis/etiology/radiography ; Tomography, X-Ray Computed

PURPOSE: Protein C deficiency is an autosomal recessive disorder, which predisposes the patient to potentially blinding and widespread lethal thromboembolic complications, especially in the homozygous type. We here report the first Korean case of ophthalmic involvement and its surgical treatment in homozygous protein C deficiency. METHODS: A 3.4kg, full term girl was born by normal delivery but showed bilateral leukocoria on day 2. Laboratory results disclosed a very low protein C activity level (10%) in the patient and moderately decreased levels in the other family members. Ophthalmic examination showed bilateral corneal opacity and shallow anterior chamber. B-scan ultrasonography which showed intravitreal mass lesions without microphthalmos and a funnel-shaped retinal detachment suggested bilateral retinal dysplasia. RESULTS: As the eyes were under progression of secondary glaucoma, bilateral lensectomies were performed at 2 months old and corneal opacity was regressed to some degree. However, at 14 months old, the left eye showed moderate corneal opacity with a band keratopathy. CONCLUSIONS: Although visual outcome was very poor after surgery, we could impede or slow down the progression of secondary glaucoma and save the eyeballs in the infant with homozygous protein C deficiency.
Anterior Chamber/ultrasonography ; Cataract/etiology ; Female ; Glaucoma/*etiology ; *Homozygote ; Humans ; Infant, Newborn ; Lens, Crystalline/surgery ; Protein C Deficiency/*complications/*genetics ; Retinal Diseases/*etiology

OBJECTIVETo investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage.

METHODSFifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombin III (AT-III), as well as activated protein C resistance (APC-R). The control group consisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for, measuring serum activity of protein C, protein S, AT-III, and APC-R. Patients with positive APC-R were tested for factor V (FV) Leiden gene mutation by PCR-RFLP method.

RESULTSOf the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-III deficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-III deficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FV Leiden gene mutation was identified in all the patients with positive APC-R results. Late spontaneous abortion cases had higher incidence of anticoagulation protein defect than the early cases.

CONCLUSIONAnticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurring in late stage of pregnancy.

Abortion, Habitual ; blood ; etiology ; Activated Protein C Resistance ; blood ; complications ; genetics ; Adult ; Antithrombin III ; metabolism ; Antithrombin III Deficiency ; blood ; complications ; Factor V ; genetics ; Female ; Humans ; Point Mutation ; Protein C ; metabolism ; Protein C Deficiency ; blood ; complications ; Protein S ; metabolism ; Protein S Deficiency ; blood ; complications

The purpose of this study was to evaluate the early outcome of endovascular management in patients with iliofemoral deep venous thrombosis (DVT) due to iliac vein compression syndrome (IVCS) and protein C and/or S deficiency. Between September 2000 and January 2003, catheter-directed thrombolysis was performed in 11 patients with a diagnosis of acute iliofemoral DVT: 7 with protein C and/or S deficiency and 4 without protein C and/or S deficiency. After thrombolysis, the diagnosis of IVCS was confirmed in 6 patients: 4 with protein C and/or S deficiency and 2 without protein C and/or S deficiency. Further intervention consisted of angioplasty and stent placement was performed. Four patients with IVCS and protein C and/or S deficiency were included in this study. The immediate technical and clinical success rates were 100% in all 4 patients. There were no complications or clinically detectable pulmonary emboli. This initial experience suggests that endovascular management of iliofemoral DVT due to IVCS in patients with protein C and/or S deficiency is safe and effective.
Adult ; Aged ; Female ; Humans ; Iliac Vein ; Male ; Middle Aged ; Plasminogen Activators/administration & dosage ; Protein C Deficiency/*complications ; Protein S Deficiency/*complications ; Research Support, Non-U.S. Gov't ; *Thrombolytic Therapy ; Treatment Outcome ; Urinary Plasminogen Activator/administration & dosage ; Venous Thrombosis/*complications/*drug therapy