Protein C and S are vitamin K-dependent natural anticoagulants. They play a major role in hemostasis by degrading the activated factor V and factor VIII. Deficiencies of protein C and protein S are associated with increased risk of thrombotic events. The combined occurrence of protein C and S deficiency has been rarely reported. We report a 6-year-old boy with Budd-Chiari syndrome due to combined protein C and protein S deficiency. He was managed with low molecular weight heparin and discharged on long-term warfarin therapy.

Protein S deficiency, the protein C cofactor main physiological inhibitor of coagulation, is a thrombophilic state with various events from thrombosis to miscarriage in pregnant women. The context of hypercoagulability and hyperfibrinolysis during pregnancy induced in deciency women, an increased risk of miscarriage and his recurrence. We report the case of a 33 year-old woman whose diagnosis of protein S deficiency was made at the waning of an assessment of repeated spontaneous abortions.

When cerebral infarction develops during pregnancy, treatment without adverse effects must be considered not only for the mother but also for the fetus. Because pregnant women were excluded from many clinical trials, clear treatment guidance for them is not shown in the package inserts or guidelines of many drugs. We report the case of a 35-year-old woman (gravida 3, para 2) who developed sudden onset of left visual field defect, left hemiparesis, and dysesthesia over the left forearm during her fourth month of pregnancy. Brain diffusion-weighted MRI showed high intensity areas in the right occipital lobe, and magnetic resonance angiography revealed an occlusion of the right posterior cerebral artery. She was treated with an intravenous injection of recombinant tissue plasminogen activator 2 h 55 min after symptom onset, and the visual field and sensorimotor deficits improved. MRA obtained 3 days after the onset showed recanalization of the right posterior cerebral artery. We also conducted electrocardiography, neck vascular ultrasound, cardiovascular ultrasound, transcranial Doppler recordings from the temple area, and laboratory examinations for complete blood count, biochemistry, coagulation factors, endocrine secretion, and autoantibodies. Reduced protein S activity (35%) along with high intensity transient signals on transcranial Doppler indicated microemboli to be the embolic source. All other tests were negative. Anticoagulation therapy was initiated to prevent recurrence. She was initially given intravenous heparin, and then switched to warfarin therapy at 15 weeks of gestation. The patient delivered a healthy infant via caesarean section. Although reports and experiences of thrombolytic therapy with injection of recombinant tissue plasminogen activator during pregnancy remain scant, this therapy might be carefully used, especially after due consideration and understanding of the risks and benefits for both mother and fetus.

A systematic study of thrombophilia markers in a large series of patients with cerebral venous thrombosis (CVT) from India is scarce. The present study was undertaken to know the prevalence of common hereditary thrombophilia in a large series of CVT patients from India. Six hundred and twelve (354 men, 219 women and 39 children) consecutive patients with CVT admitted to various hospitals in Mumbai between 2001 and 2010 were investigated for the common thrombophilia markers, that is, protein C (PC), protein S, antithrombin (AT), and factor V Leiden (FVL) mutation. The main presenting clinical manifestations included papilledema (62%), headache (62%), hemiparesis (48%), seizures (31%), and cranial nerve palsy (7%). All the patients were managed with heparin followed by warfarin during the succeeding 6 months. Superior sagittal sinus thrombosis was the commonest site (74%) followed by cortical venous thrombosis (15%). Associated clinical pathologies were dehydration, sepsis, pregnancy and puerperium, malaria, and tuberculosis; but in the majority of patients, there was no obvious cause. Eighteen percent of the patients had any of the thrombophilia markers studied; PC deficiency was the commonest thrombophilia marker followed by deficiency of protein S, FVL mutation and AT deficiency. The men below 45 years with PC deficiency (P = 0.03) and women with protein S deficiency were significantly higher (P = 0.04). In conclusion, CVT is not an uncommon cause of neurological deficit as was presented in earlier reports. Pregnancy and puerperium-related CVT was much less common. Thrombophilia markers accounted for approximately one-fifth of the patients. Death due to CVT has shown remarkable reduction (13%) because of early diagnosis and appropriate anticoagulation.

Thromboses (VTE) in children were associated with medical diseases with and without acquired or inherited thrombophilic risk factors (IT). Disease recurrence rates vary between 3% in children with a first event during the neonatal period and 21% in children with idiopathic VTE. Recently reported systematic reviews showed significant associations between VTE and factor V G1691A or factor II G20210A mutations, protein C, protein S and antithrombin deficiency, more pronounced when combined IT were involved. The factor II G20210A mutation, protein C, protein S, and antithrombin deficiency did also play an important role at VTE recurrence. Primarily asymptomatic family members of pediatric VTE index cases showed annual VTE incidence rates of 2.82% in carriers of antithrombin, protein C, or protein S deficiency, 0.42% and 0.25% in carriers of the factor II G202010A or V G1691A mutation, and 0.10% in relatives with no IT.

Antithrombin is the major inhibitor of blood coagulation, primarily inactivating thrombin and factor Xa. Inherited antithrombin deficiency is associated with an increased risk of thromboembolism. Its prevalence is estimated to be about 0.2% in the general healthy population, whereas it is 2% in patients with a history of thrombosis. We previously demonstrated thrombosis patients receiving therapeutic dosage of low-molecular-weight heparin having a lower antifactor Xa activity than originally estimated. In those patients, mutations in the AT gene (SERPINC1) were detected despite normal antithrombin activity. Thus we concluded that prevalence of antithrombin mutations might be higher than previously calculated. The aim of the present study was to investigate the prevalence of hereditary antithrombin mutations by analyzing the antithrombin gene in patients with a history of thromboembolism. Mutation analyses were performed by direct sequencing of SERPINC1 in 150 patients (aged <40 years) with thromboembolism and normal antithrombin levels. Patients with thrombophilic defects [factor V Leiden (G1691A), prothrombin (G20210T) mutation, protein C deficiency, protein S deficiency, and antiphospholipid antibodies] were excluded. The results were compared with those of 150 healthy controls without any personal history of thrombosis. Mutation analyses of all seven antithrombin exons revealed five (3.5%) patients with antithrombin mutations: three different heterozygous missense mutations were found in exon 2 and one (in two patients) in exon 7. Prevalence of inherited antithrombin mutations in thrombosis patients is higher than previously estimated. Functional antithrombin tests are unable to detect all clinically relevant antithrombin defects.

Cerebral sinodural thrombosis (CSDT) is a rare complication of minor head trauma in children. Despite recommendations, anticoagulation is frequently withheld. We aimed to evaluate the etiology, clinical presentation, risk factors, diagnosis, treatment, and outcome of pediatric CSDT following minor head trauma, and specifically to evaluate factors associated with anticoagulation use following minor head trauma in pediatric patients with CSDT. A literature search from 1990 to 2012 identified manuscripts discussing epidemiology, risk factors, clinical presentation, management, and outcome in pediatric patients with CSDT subsequent to minor head trauma. One pediatric patient diagnosed with CSDT following minor head trauma in our institution was also included in the study. There were 18 pediatric patients with CSDT following minor trauma, including the current patient. Mean patient age was 7.8years (range 23months-15years). There was a strong female predominance (2.4:1). Vomiting and headache were the most common symptoms. Five patients had pre-existing risk factors (gastroenteritis, protein S deficiency, estroprogestenic medication, elevated antiphospholipid antibodies, malnutrition). Anticoagulation was administered to six patients with additional risk factors, severe symptoms, or deterioration. There was no mortality, 12 patients recovered fully, and four patients improved with residual symptoms. One patient required lumboperitoneal shunt placement. Pediatric CSDT is a rare complication of minor head trauma, with variable presentation. Anticoagulation has generally been reserved for patients suffering from severe symptoms, for those who deteriorate neurologically during observation, and for those who suffer from a concomitant prothrombotic disorder.

Inherited thrombophilias are thought to play an important role in the cause of pulmonary embolism and its recurrence. Ninety of 281 patients objectively diagnosed as pulmonary embolism between 2006 and 2009 were included in the study. The screening for thrombophilia included mutations of factor V Leiden (FVL), prothrombin (PTM) G20210A, methylene tetrahydrofolate reductase C677T-A1298C, the serum levels of antithrombin III, protein C, protein S, factor VIII and activated protein C resistance. Forty-two male (46.7%) and 48 female (53.3%) patients had a mean age of 62.6 ± 13.4 years. Patients with common thrombophilias comprised 30% of all cases (FVL: 19.1%, PTM G20210A: 3.4%, antithrombin III deficiency: 1.1%, protein C deficiency: 5.7%, protein S deficiency: 13.6%). A significant association between recurrence of pulmonary embolism (10 patients, 12.2%) and protein S deficiency was established (P = 0.040). Serum level of protein C was also significantly lower in the subgroup of recurrent pulmonary embolism (P = 0.049). FVL and PTM mutations were high in cancer patients; the presence of inherited thrombophilia was low with risk factors of surgery and immobilization. Genetic risk factors were high in patients with pulmonary embolism. Protein C and S deficiencies may play a role in pulmonary embolism recurrence. DVT or family history of pulmonary embolism was not found to be related to inherited thrombophilias. Surgery and immobilization were thought not to have priorities for detection of genetic risk factors. The high percentages of FVL and PTM mutations in cancer patients should be considered.

A 32-year-old man presented overnight to the accident and emergency unit with mild breathlessness on exertion. He was found to be hypoxic on room air and his chest x-ray revealed areas of patchy lung consolidation. He was given intravenous antibiotics for presumed community-acquired pneumonia. Unfortunately his condition deteriorated and he remained significantly hypoxic despite high-flow oxygen with ECG evidence of right heart strain. Further questioning revealed a history of protein S deficiency and a strong family history of venous thromboembolic disease. An urgent CT pulmonary angiogram showed an evidence of massive pulmonary embolism and the patient was successfully thrombolysed.