We report structural changes in the retina of an adolescent diagnosed with the concomitant two temporal cilioretinal artery occlusion (CLRAO) with impending central retinal vein occlusion (CRVO) along with mild protein C deficiency. An 18-year-old girl came to the emergency room with sudden onset painless loss of vision in her right eye. On comprehensive ophthalmic examination, she had a pale superior-temporal retina with spongy macular edema corresponding to two temporal CLRAO and blurred disc margins with mild disc swelling and mild tortuosity of retinal veins all over the retina with few superficial hemorrhages in the right eye corresponding to impending CRVO. Optimal coherence tomography (OCT) showed thickening of the nerve fiber layer in the superior-temporal quadrant involving some part of the macula in the right eye. Perimetry showed a right eye visual field defect in the inferior nasal quadrant. Her coagulation profile was normal but her autoimmune profile was suggestive of mild protein C deficiency. Immediately she was started on anticoagulants. After one month, her visual acuity improved from finger counting close to face to 6/9 with treatment. Over a period of one month, retinal and OCT changes recovered with the same perimetry findings as earlier. This case shows how prompt treatment resulted in dramatic improvement in the form of good visual outcomes.

Acute liver failure is an uncommon presentation in the clinic. Common causes for acute liver failure include viral hepatitis and drug-related hepatotoxicity. However, acute liver failure due to Budd-Chiari syndrome is rare. This case highlights the importance of necessary constrast-enhanced imaging studies to rule out vascular etiologies of acute liver failure, in addition to common causes like viral or drug-induced hepatic failure. We present a case of a male Chinese patient who presented with nausea, vomiting, fatigue, and fever after eating a large amount of fatty food. Six days after hospitalization, the patient developed acute liver failure and hepatic encephalopathy. Contrast-enhanced computerized tomography and ultrasound examinations revealed thromboses in the hepatic veins and inferior vena cava. Further testing also showed decreased protein C activity. Therefore, a diagnosis of Budd-Chiari syndrome secondary to protein C deficiency was made. He received supportive care and a transjugular intrahepatic portal shunt. Hepatic function, coagulation panel results, and clinical presentations gradually returned to normal. Budd-Chiari syndrome from protein C deficiency could be a rare but valid cause of acute liver failure in Chinese patients.

Hereditary protein C deficiency is a chromosomal genetic disease caused by mutations in the protein C gene,which can lead to venous thrombosis and is mostly related to mutations in exons 4-9 and intron 8.Fatal pulmonary embolism caused by mutations in the protein C gene is rare,and the treatment faces great challenges.This article reports a case of fatal pulmonary embolism caused by a frameshift mutation in exon 8 of the protein C gene and summarizes the treatment experience of combining extracorporeal membrane oxygenation (for respiratory and circulatory support) with interventional thrombectomy,providing a basis for the diagnosis and treatment of this disease.
遗传性蛋白C缺陷症是由蛋白C基因突变引起的一种染色体遗传病,可导致静脉血栓形成,多与外显子4~9和内含子8的突变有关。蛋白C基因突变引起的致死性肺栓塞罕见,治疗面临巨大挑战。本文报道1例由蛋白C基因8号外显子移码突变引起的致死性肺栓塞,采用体外膜氧合进行呼吸、循环支持,并成功实行介入取栓的救治经验,为该疾病的诊断及救治提供参考。.

UNASSIGNED: Protein C (PC) is an anticoagulant that is encoded by the PROC gene. Validation for the function of PC was carried out in mouse models.
UNASSIGNED: In this study, autosomal recessive PC deficiency (PCD) was selected as the target, and the specific mutation site was chromosome 2 2q13-q14, PROC c.1198G>A (p.Gly400Ser) which targets G399S (GGT to AGC) in mouse models. To investigate the role of hereditary PC in mice models, we used CRISPR/Cas9 gene editing technology to create a mouse model with a genetic PCD mutation.
UNASSIGNED: The two F0 generation positive mice produced using the CRISPR/Cas9 gene editing technique were chimeras, and the mice in F1 and F2 generations were heterozygous. There was no phenotype of spontaneous bleeding or thrombosis in the heterozygous mice, but some of them were blind. Blood routine results showed no significant difference between the heterozygous mice and wild-type mice (P > 0.05). Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged in the heterozygous mice, while the level of fibrinogen content (FIB) decreased, suggesting secondary consumptive coagulation disease. The protein C activity of heterozygous mice was significantly lower than that of wild-type mice (P < 0.001), but there was no significant difference in protein C antigen levels (P > 0.05). H&E staining showed steatosis and hydrodegeneration in the liver of heterozygous mice. Necrosis and exfoliated epithelial cells could be observed in renal tubule lumen, forming cell or granular tubules. Hemosiderin deposition was found in the spleen along with splenic hemorrhage. Immunohistochemistry demonstrated significant fibrin deposition in the liver, spleen, and kidney of heterozygous mice.
UNASSIGNED: In this study, heterozygotes of the mouse model with a PC mutation were obtained. The function of PC was then validated in a mouse model through genotype, phenotype, and PC function analysis.

Protein C (PC) is a key component of the vitamin K-dependent coagulation pathway. It exerts anticoagulant effects by inactivating factors V and VIII. Acquired or inherited PC deficiency results in a prothrombotic state, with presentations varying from asymptomatic to venous thromboembolism. However, there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events, such as myocardial infarction and ischemic stroke. This editorial focuses on the association between PC deficiency and thromboembolism, which may provide some insights for treatment strategy and scientific research.

Congenital protein C (PC) deficiency is one type of hereditary thrombosis. Patients with hereditary thrombosis are at high risk for thrombosis in the perioperative period, but a standard management strategy has not been established. Here we report a case of perioperative management of a fracture in a child with homozygous congenital PC deficiency. The patient was a 3-year-old boy who was diagnosed with congenital PC deficiency at birth. He sustained a traumatic supracondylar fracture of the right humerus and underwent emergency surgery. To prepare for open surgery for fixation of the fracture, warfarin was discontinued, and an activated PC (APC) concentrate was used in combination with vitamin K antagonism. However, warfarin was administered during the scheduled nail extraction because the operation was minimally invasive. No thrombotic or bleeding complications occurred in either operation. In emergency surgery in patients with congenital PC deficiency, the combination of vitamin K and APC concentrate is considered a maintenance option for PC deficiency. Postoperative PT-INR control was difficult in our patient due to the administration of vitamin K and withdrawal of warfarin, and this issue must be addressed in the future. Further case experience is desirable to standardize perioperative management.

BACKGROUND: Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein S and antithrombin deficiencies.
METHODS: A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People\'s Hospital. The proband, a 12-year-old female, was admitted to the hospital in December 2020 with a complaint of pain in the left lower limb for four days. The examination found that the PC activity was 53%, and B-ultrasound showed bilateral thrombosis of the great saphenous vein in the thigh segment. The proband\'s younger brother, a 10-year-old male, was admitted to the hospital in January 2021 due to right lower limb pain for two weeks. PC activity is 40%. B-ultrasound showed superficial venous thrombosis in the left lower limb and upper limb. Both siblings suffered from thalassemia and underwent splenectomy before recurrent thrombosis occurred. The proband\'s mother was asymptomatic, and her PC activity was 45%. Both cases were treated with warfarin anticoagulation, and their symptoms improved. The proband\'s mother was found to have a heterozygous mutation at this locus through Sanger sequencing.
CONCLUSIONS: Protein C deficiency should be considered for venous thromboembolism in childhood. The heterozygous mutation 1204 A > G in PROC exon 9 in this family is reported for the first time.

UNASSIGNED: The development of new dural arteriovenous fistulas (DAVFs) at another location following endovascular treatment of cavernous sinus DAVFs (CSDAVFs) are extremely rare. Our aim is to review cases of de Novo DAVFs that occurred after treatment of CSDAVFs at our institution and those reported in the literature.
UNASSIGNED: We reviewed all cases of CSDAVFs evaluated by 2 experienced neuroradiologists. A literature search was performed using the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines focusing on De Novo DAVFs following the endovascular treatment of cerebrovascular malformations. Addition articles were searched through the reference lists of the included articles.
UNASSIGNED: From June 2004 and September 2019., we identified 3 (2.5%) cases of De Novo DAVFs occurred after endovascular treatment or spontaneous obliteration of CSDAVFs from 119 treated CSDAVFs at our institute. Our review yielded 9 articles involving 12 patients with 15 de novo DAVFs, including our 3 patients. The mean age was 55.08 ± 12.9 years (range 43-69), 83.3% were females (n = 10). The new remote DAVFs occurred after endovascular treatment of CSDAVFs in 10 (83.3%) patients. The de novo DAVFs occurred following spontaneous complete regression in 2 (16.7%) patients. All de novo DAVFs developed after complete obliteration of treated CSDAVFs.
UNASSIGNED: Sinus thrombosis and elevated venous pressure may play an important role in the pathogenesis of a de novo DAVF formation. In addition, thrombophilic abnormalities and the use of contraceptives may contribute to sinus thrombosis, leading to the development of the second remote DAVF after treatment of CSDAVFs.

OBJECTIVE: To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) deficiency and explore their association with vascular thromboembolism.
METHODS: The clinical data of four patients with PC deficiency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the probands. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation.
RESULTS: Thrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c.541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. In particular, c.1146_1146delT heterozygous deletion mutations not reported previously. Conservativeness and pathogenicity analyses confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. According to the American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants, c.1146_1146delT was rated as pathogenic (PVS1 + M2 + PM4 + PP1 + PP3 + PP4).
CONCLUSIONS: The identified mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC deficiency exhibit considerable diversity.

Neonatal purpura fulminans (PF) is an uncommon skin disorder characterized by acute disseminated intravascular coagulation, tissue necrosis, and small vessel thrombosis. Here, we present a case of a seven-day-old male who was admitted to the Neonatal Intensive Care (NICU) Unit at Gaafar Ibn Auf Tertiary Hospital, in January 2023. He presented with black bullous lesions on the plantar surface of the left foot, deep bluish discoloration over the right buttock and right lower abdomen, and gangrenous changes in the right foot with clear demarcation. Birth history was not significant other than mild pallor and icterus. His blood workup was consistent with severe anemia, thrombocytopenia, elevated prothrombin time, and partial thromboplastin time with decreased protein C and S levels; blood culture yielded no growth. A Doppler ultrasound scan of lower extremities confirmed distal occlusion of the right dorsalis pedis artery. The abdominal ultrasound revealed a free left renal bed and left-sided renal agenesis. We came to a diagnosis of neonatal PF and started administering blood and fresh frozen plasma and subcutaneous heparin injections, but unfortunately, the patient eventually passed away. Hence, we decided to report this case to emphasize the significance of the clinical picture in assisting with early diagnosis, despite limited access to genetic testing. We also want to highlight the importance of a \"high index of suspicion\" that might be mandatory for better outcomes.