Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Clinical phenotype and gene mutation analysis of 12 patients with hereditary protein C deficiency in different families / 中华血液学杂志

Objective: To investigate the molecular pathogenesis and clinical features of unrelated 12 patients with inherited coagulation protein C (PC) deficiency in Chinese population. Methods: The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and enzyme linked immunosorbent assay, respectively. The nine exons and flanking sequences of the protein C (PROC) gene were amplified by polymerase chain reaction with direct sequencing, and the suspected mutations were validated by reverse sequencing (clone sequencing for deletion mutations) . Results: The PC:A of the 12 probands decreased significantly, ranging from 18% to 55%, and the PC:Ag of the 10 probands decreased significantly. Eleven mutations were found, out of which four mutations [c.383G>A (p.Gly128Asp) , c.997G>A (p.Ala291Thr) , c.1318C>T (p.Arg398Cys) , and c.532G>C (p.Leu278Pro) ] were discovered for the first time. Six mutations were in the serine protease domain, four mutations were located in epidermal growth factor (EGF) -like domains, and one mutation was located in activation peptide. There were two deletion mutations (p.Met364Trp fsX15 and p.Lys192del) , and the rest were missense mutations. Mutations p.Phe181Val and p.Arg189Trp were identified in three unrelated families. All mutations may be inherited, and consanguineous marriages were reported in two families. Among the probands, nine cases had venous thrombosis, two cases had poor pregnancy manifestations, and one case had purpura. Conclusion: Patients with PC deficiency caused by PROC gene defects are prone to venous thrombosis, especially when there are other thrombotic factors present at the same time.

Neonatal-onset protein C deficiency: case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features, diagnosis, treatment and genetic characteristics of neonatal-onset protein C deficiency (PCD).Methods:The clinical data of a newborn patient with severe PCD admitted to our neonatal department was reviewed. Databases including CNKI, Wanfang Database, CMB, VIP database, PubMed, Embase and SCI database were searched using" infantile", " neonate ", "newborn", "protein C deficiency" and "purpura fulminans" as key words. Published cases of PCD were analyzed.Results:The patient was a full-term female infant who developed multiple symptoms within 2 days after birth. The symptoms included thrombocytopenia, intracranial hemorrhage, purpura fulminans (PF), disseminated intravascular coagulation (DIC), celiac hemorrhage, hypertension, portal and iliac vein thrombosis, purulent meningitis and retinal detachment. Protein C activity was less than 10%. Genetic tests showed compound heterozygous mutations c.314G>T (p.c105f) of paternal origin and c.1218G>A (p.m406i) of maternal origin in PROC gene. According to ACMG guidelines, the mutations were strongly suspected pathogenic variants and consistent with an autosomal recessive (AR) inheritance pattern. The patient was discharged after 6 weeks of treatment at parents' request of withdrawal. A total of 25 articles on 29 patients with relatively complete clinical data were retrieved, including 18 males and 11 females. 4 patients were preterm and 25 full-term. 28 patients showed symptoms within 7 days after birth. The common clinical features were cutaneous PF and splanchnic thrombi. 22 cases documented protein C activity and ranged from 0 to 25%. 16 patients had PROC gene abnormalities and compound heterozygous mutations were found in 10 patients. Among the 22 patients with prognostic data, 11 died (9 within 3 months after birth), the remaining survivors suffered from sequelae including severe intellectual motor development disorder, epilepsy and blindness.Conclusions:The main clinical manifestations of neonatal-onset PCD include PF, DIC, multi-organ hemorrhage and thrombus. The disease is acute and severe, with rapid progression, poor prognosis and high fatality rate. Protein C activity and PROC gene testing may help establish the diagnosis.

Incidence of thrombophilia in patients with recurrent pregnancy loss

Background: Approximately 1-3% of women of reproductive age suffer from recurrent pregnancy loss. Objective of this study was to evaluate the association between recurrent pregnancy loss and thrombophilia.Methods: This is a descriptive study, involving retrospective analysis of patients with recurrent pregnancy losses. Patients with recurrent pregnancy loss in whom associated morbidity factors were excluded underwent screening for both acquired and inherited thrombophilia.Results: A total of 20 patients were screened for acquired and inherited thrombophilia with recurrent pregnancy loss. Thrombophilia was diagnosed in 70% cases. Out of which, anticardiolipin antibodies was found positive in 57% of patients, protein C 7% and protein S deficiency was observed in 35% cases.Conclusions: Thrombophilias are associated with recurrent pregnancy loss. Patients in whom other associated morbid factors are excluded, should be offered screening for thrombophilia. Multidisciplinary management involving hematologist is vital for management.

Protein C and S deficiency as a cause of mesenteric thrombosis: Differential diagnosis of systemic vasculitis / Deficiencia de proteínas C y S como causa de trombosis mesentérica: diagnóstico diferencial de las vasculitis sistémicas

ABSTRACT Acute mesenteric ischemia is a medical emergency that accounts for less than 1/1000 hospital admissions. The disease affects adults older than 50 years predominantly with cardiac compromise, in whom the presence of acute abdominal pain is the cardinal manifestation, and should make the clinician suspect this entity. Its presentation in adolescents is unusual; therefore, in these cases, the possibility of an underlying thrombophilia should be part of the differential diagnosis. The case is presented here of a young female with a protein C and S deficiency as the cause of mesenteric thrombosis.

RESUMEN La isquemia mesentérica aguda es una urgencia médica que se presenta en menos de 1/1.000 ingresos hospitalarios. Es una entidad clínica infrecuente, predominante en adultos mayores de 50 arios con afectación cardíaca, en quienes la presencia de dolor abdominal agudo es la manifestación cardinal y debería hacer sospechar dicho diagnóstico. La presentación en adolescentes es inusual, por lo que, en estos casos, la posibilidad de una trombofilia subyacente debe formar parte del diagnóstico diferencial. Presentamos el caso de una paciente joven con deficiencia de proteínas C y S como agente causal de trombosis mesentérica.

Combined central retinal artery occlusion and central retinal venous occlusion with bilateral carotid artery disease in apatient with protein C deficiency

@#Central retinal artery occlusion and central retinal venous occlusion are rare entities of retinal vascular disorders that can cause sudden visual loss and combined occurrence results in devastating outcomes. The role of protein C deficiency is well established in venous thrombosis however the occurrence of concurrent arterial thrombosis is rare and the combination in association with carotid artery occlusion is an exceptionally rare occurrence. Here we report a case of protein C deficiency presenting as combined central retinal artery occlusion and central retinal venous occlusion with bilateral carotid artery disease

Virus de inmunodeficiencia humana: ¿estado de hipercoagulabilidad? Presentación de dos casos / Is AIDS a prothrombotic entity? Report of two cases

La infección por VIH ha sido reconocida en la actualidad como una condición protrombótica, reportándose en pacientes con SIDA 10 veces mayor riesgo de desarrollo de eventos tromboembólicos de los sistemas arterial y venoso; la literatura reciente ha estimado una incidencia entre el 0.26% y 7.6 %; dicha incidencia se describe asociada a infecciones. oportunistas y/o malignidades. Una variedad de mecanismos potenciales relacionados con factores del hospedador, el virus y el TARV (tratamiento antiretroviral), están implicados en el estado de hipercoagulabilidad en pacientes con SIDA, cuya fisiopatología conduce a alteraciones en la respuesta inflamatoria y de la cascada de coagulación que no han sido bien dilucidadas; sin embargo, incluye la presencia de anticuerpos anticardiolipinas, disminución de anticoagulantes naturales, y otros factores independientes que en conjunto originan morbi-mortalidad creciente si dicha predisposición a eventos trombóticos no es reconocida por el médico. Los autores de este artículo describen 2 casos de eventos trombóticos en pacientes con síndrome de inmunodeficiencia humana hospitalizados en el Servicio de Medicina Interna de Hospital Universitario de Caracas(AU)

AIDS infection has now been recognized as a prothrombotic condition reported in patients with this disease, and have been found 10 times at greater risk of developing thromboembolic events with systemic involvement. Recent literature has estimated an incidence between 0.26% and 7.6%, also described in association with opportunistic infections and / or malignancies. A variety of potential mechanisms related to host factors, virus and antiretroviral therapy (ART) are implicated in the hypercoagulability status in HIV-positive patients, the pathophysiology leading to alterations in the inflammatory response and the coagulation cascade. It has not been well understood and includes the presence of anticardiolipin antibodies, reduction of natural anticoagulants, and other independent factors that lead to increased morbidity and mortality if such predisposition to thrombotic events is not recognized by the clinician. The authors of this article describe 2 cases of thrombotic events in patients with human immunodeficiency syndrome hospitalized in the Hospital Universitario of Caracas, Venezuela(AU)

Central Retinal Vein Occlusion in Young Healthy Patients and the Role of Thrombophilia in Pathogenesis

PURPOSE: We report two young patients who developed central retinal vein occlusion (CRVO) without any systemic disease, and various thrombophilia tests were performed to determine the etiology. CASE SUMMARY: Two young patients, a 22-year-old female and a 23-year-old male, who had acute vision loss were diagnosed with nonischemic CRVO via fluorescein angiography. They had no other disease and no common risk factors for CRVO. We performed various tests to determine the thrombophilic risk factors and discovered a transient decrease in protein S antigen and protein C antigen in the female and male patients, respectively. CONCLUSIONS: CRVO in young patients without systemic disorders may have different mechanisms in the pathology and thus additional laboratory tests to determine thrombophilic disorders are necessary.

Cerebral Palsy due to Intracranial Hemorrhage Caused by Consumptive Coagulopathy in Protein C Deficiency: A Case Report / 대한소아신경학회지

Protein C (PROC) is a potent anticoagulant inactivating coagulation factors Va and VIIIa. PROC deficiency is very rare condition inherited as an autosomal dominant or recessive trait, and associated with various thromboembolic and ischemic conditions. Moreover, severe form of PROC deficiency can cause fatal hemorrhagic complications due to consumptive coagulopathy. We reported two children with hemorrhagic stroke who were diagnosed as severe PROC deficiency caused by two different types of compound heterozygous PROC gene mutations. We described results of laboratory tests, genetic analysis, brain magnetic resonance images, and functional outcomes. Both children received prophylactic anticoagulation therapy and presented with purple-colored skin lesions during rehabilitation. Purpura fulminans caused by insufficient anticoagulation should be differentiated from hematoma caused by excessive anticoagulation therapy in these children.

Cerebral Palsy due to Intracranial Hemorrhage Caused by Consumptive Coagulopathy in Protein C Deficiency: A Case Report / 대한소아신경학회지

Protein C (PROC) is a potent anticoagulant inactivating coagulation factors Va and VIIIa. PROC deficiency is very rare condition inherited as an autosomal dominant or recessive trait, and associated with various thromboembolic and ischemic conditions. Moreover, severe form of PROC deficiency can cause fatal hemorrhagic complications due to consumptive coagulopathy. We reported two children with hemorrhagic stroke who were diagnosed as severe PROC deficiency caused by two different types of compound heterozygous PROC gene mutations. We described results of laboratory tests, genetic analysis, brain magnetic resonance images, and functional outcomes. Both children received prophylactic anticoagulation therapy and presented with purple-colored skin lesions during rehabilitation. Purpura fulminans caused by insufficient anticoagulation should be differentiated from hematoma caused by excessive anticoagulation therapy in these children.

Early cirrhosis in a young female with protein C deficiency: An extremely unusual case report with review.

Protein C deficiency is a well recognized risk factor for development of venous thromboembolism but has never been reported to be associated with development of liver cirrhosis .We report a case of a 26 years old female who presented with multiple thrombosis involving superior mesenteric vein ,main portal vein and multiple cerebral veins. Liver biopsy done was reported as cirrhosis possibly due to Wilson’s disease. However no improvement was seen with D penicillamine and patient’s condition detiorated. Further, work up of patient revealed absence of Protein C levels in the plasma. So finally the case was diagnosed as Cirrhosis liver with Protein C deficiency as the likely etiology. We conclude that Protein C deficiency should be investigated in patients with cirrhosis with thrombotic lesions of unknown etiology.

A Case of Cerebral Venous Thrombosis in a Patient with Graves' Disease / 고신대학교의과대학학술지

Superior sagittal sinus thrombosis is an uncommon disease, and 25% of cases are considered to be idiopathic. Hypercoagulability, local bloodstream stasis, and vessel wall abnormalities may contribute to the development of this condition. The thyrotoxic phase of Graves’ disease is associated with venous thrombosis caused by hypercoagulability, which is in turn induced by increased levels of homocysteine and factor VIII and decreased fibrinolytic activity. Here, we report the case of a 39-year-old male who presented with superior sagittal sinus thrombosis and concomitant hyperthyroidism.

Diagnosis of Severe Protein C Deficiency Confirmed by Presence of Rare PROC Gene Mutation

Protein C (PROC) deficiency is caused by mutations in the PROC gene on chromosome 2q14.3. Patients with PROC deficiency typically present distinguished purpura, intracerebral and intravascular coagulopathy, and ophthalmologic complications. Here, we report a rare severe form of PROC deficiency resulting from a compound heterozygosity in PROC. The patient was a 5-day-old female neonate born at 39 weeks of gestation with a birth weight of 2,960 g. She was transferred to our hospital with running a fever at 38.5℃ and with dark red patches on her feet. At admission, a complete blood count showed no specific findings, but levels of PROC and protein S were abnormally low (1% and 68%, respectively). Magnetic resonance imaging revealed intracerebral hemorrhaging and parenchymal damage with dysplasia of the brain. Ophthalmologic examination revealed vitreous hemorrhaging with retinal detachment. Genetic testing revealed a missense mutation (Arg211Trp) and a frameshift mutation (Gly239Serfs*8) in PROC, inherited from the father and mother, respectively. The patient recovered from purpura after undergoing ventriculoperitoneal shunting and treatment with fresh frozen plasma, warfarin sodium, and PROC concentrate. This is the first report of severe neonatal PROC deficiency with purpura fulminans, vitreous hemorrhage, and intracerebral hemorrhage confirmed via PROC genetic testing, which identified a rare compound heterozygosity of PROC.

Trombofilias hereditarias / Hereditary Thrombophilia

Las trombofilias hereditarias suponen un grupo de enfermedades que predisponen al desarrollo de enfermedad tromboembólica arterial y venosa, debido a déficit o ganancia de función de factores anticoagulantes o procoagulantes incrementando de manera significativa la morbilidad y mortalidad en la población adulta y pediátrica. La expresión y penetrancia genética de este grupo de enfermedades es diversa, y las formas de presentación clínica varía desde la purpura fulminans neonatal hasta episodios tromboembólicos recurrentes a edades tempranas y efectos adversos en el embarazo. El screening no es rutinario en pacientes con cuadros tromboembólicos y sus indicaciones son precisas, en especial personas menores a los 45 años, con cuadros recurrentes, y abortos o muertes fetales a repetición sin causa específica. El tratamiento es basado de acuerdo a la presentación del cuadro clínico, sin embargo la anticoagulación convencional es ampliamente utilizada en el manejo de este grupo de pacientes.

Inherited thrombophilia represent a group of diseases that predispose to the development of arterial and venous thromboembolic disease due to deficiency or gain of function of anticoagulant or procoagulant factors, increasing significantly the morbidity and mortality in the adult and pediatric population. Expression and genetic penetrance to this group of diseases is diverse, and the form of clinical presentation varies from the neonatal purple fulminans to recurrent thromboembolic events at a young age and pregnancy with side effects. The screening is not routine in patients with thromboembolic condition and its indications are accurate, especially in younger people than 45, with recurrent episodes of abortions or fetal deaths without specific cause. Treatment is based according to the clinical presentation of the condition; however conventional anticoagulation is widely used in the treatment of this patient group.

Bilateral Torsion of Testes with Purpura Fulminans.

Background: Purpura fulminans and bilateral perinatal testicular torsion are rare and may co-exist. Case characteristics: A 3-day-old neonate with bilateral swelling of scrotum; torsion and gangrenous changes were observed on exploration. Interventions: Left orchidectomy with preservation of right testis was done. Outcome: At 2-month follow-up, right testis showed signs of atrophy. Child developed full thickness skin lesions and died of sepsis. Message: Perinatal testicular torsion can be bilateral, and requires urgent surgical exploration.

Déficit de proteína C en un paciente con coagulación intravascular diseminada asociada a sepsis y trombosis venosa profunda: Case report / Protein C deficiency in patient with sepsis-associated disseminated intravascular coagulation and deep vein thrombosis

La coagulación intravascular diseminada es un síndrome clinicopatológico que complica a varias enfermedades graves; la sepsis es la causa más común en los pacientes pediátricos. Resulta de una anormal activación del sistema de coagulación, que conduce a la formación de trombos en la microcirculación, y al consumo de plaquetas y factores de la coagulación. Los hallazgos clínicos son variables; las hemorragias son la presentación más frecuente, seguidas de la púrpura y la gangrena de las extremidades (púrpura fulminante). Se presenta el caso de un paciente con coagulación intravascular diseminada asociada a sepsis, con trombosis venosa profunda concomitante. Los estudios permitieron diagnosticar una trombofilia hereditaria asociada a déficit hereditario de proteína C.

Disseminate intravascular coagulation (DIC) is a clinical pathological syndrome associated to several diseases. Sepsis is the most common cause in infants and children. DIC results from the anomalous activation of blood coagulation, widespread formation of thrombi in the microcirculation, and consumption of clotting factors and platelets. Clinical findings are variable; the most common is bleeding, followed by purpura and acral gangrene (purpura fulminans). We report a patient with sepsis associated-DIC and concurrent deep venous thrombosis. The diagnostic evaluation allowed to discover inherited thrombophilia associated to protein C deficiency.

Spontaneous Renal Artery Dissection in a Patient with Protein C and S Deficiency / 대한내과학회지

Spontaneous renal artery dissection without aortic dissection in normotensive patients is rarely reported. Spontaneous renal artery dissection is also an uncommon cause of renal infarction that occurs, though rarely, in patients with hypercoagulable states such as protein C and S deficiency. We report here a case of spontaneous renal artery dissection and renal infarction associated with protein C and S deficiency.

Estudio de caso a una adolescente con dependencia en la necesidad de seguridad y protección, por deficiencia de proteína C / Case Study on a teenage over-dependent on security and protection due to protein "C" deficiency

Los problemas de salud de la población infantil constituyen un reto diario para otorgar los cuidados especializados de enfermería conforme a las particularidades biológicas, psicológicas y sociales de este grupo de edad. Para afrontarlo es preciso tener conocimiento de los diferentes factores que influyen en el proceso salud-enfermedad, así como compartir con el gremio las acciones que enfermería implementa para cubrir las demandas específicas de atención. Objetivo: Dar a conocer el estudio de caso, de una adolescente femenina con deficiencia de proteína "C" con dependencia en la necesidad de seguridad y protección. Metodología: Se utilizó el Proceso Atención de Enfermería, orientado con la propuesta filosófica de Virginia Henderson, la recolección de la información se realizó mediante fuentes primarias y secundarias, se realizaron valoraciones focalizadas obteniéndose 15 diagnósticos enfermeros de los cuales 5 están en dependencia, 5 en riesgo y 5 en independencia; la realización de los mismos se hizo apoyándose en la taxonomía de la NANDA versión 2009-2011 y en el formato PES. Se detectó el grado y nivel de dependencia de acuerdo a la escala propuesta por Margot Phaneuf, y se planearon las estrategias a realizar para que ella alcanzara su independencia. Resultados: Con las intervenciones que se propusieron en el plan así como las acciones de enfermería se logró que la paciente y su cuidador primario (mamá) identificaran como enfrentar los problemas principales derivados de la pérdida de la visión y el embolismo de tal forma que se evitaron complicaciones futuras. Cabe mencionar que la participación del cuidador primario fue fundamental para mejorar el nivel de dependencia de las necesidades alteradas.

Objective: divulge the study case of a female adolescent with protein "C" deficiency and over-dependency to security and protection. Methodology: The Virginia Henderson philosophy oriented Nursing Attention Process was used. Data were collected from primary and secondary sources. Based on the NANDA 2009-2011 and the PES format, fifteen nurse assessments were made; 5 turned out to be; in dependence, 5; in risk, and 5; in independence. The degree and level of dependency was assessed according to the Margot Phaneuf proposed scale. Strategies to help the adolescent reach her independence were planned. Results: From the proposed interventions and the nursing actions, the patient and her primary care supporter (her mother) identified how to face the principal problems derived from the loss of vision and embolism, and thus future complications were avoided. The primary health supporter role was fundamental to improve the patient's dependency level.

Hereditary Thrombophilia in Korean Patients with Idiopathic Pulmonary Embolism

PURPOSE: Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated. MATERIALS AND METHODS: Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE. RESULTS: Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44+/-14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients. CONCLUSION: In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.

A Case of Superior Mesenteric Venous Thrombosis Due to Protein C Deficiency in a Patient with Duodenal Ulcer Bleeding / 대한소화기학회지

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.