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

Protein S is found in two forms in plasma; as free and functionally active protein S, and complexed to C4b-binding protein. Patients with nephrotic syndrome are at risk for arterial and venous thrombosis at various localizations, and acquired protein S deficiency due to the selective urinary loss of the free form may be a risk factor for the development of thromboembolic complications. We report a case of cerebral arterial thrombosis associated with decreased level of free protein S antigen (44%) in a 39-year-old female patient with nephrotic syndrome.
Adult ; Case Report ; Female ; Human ; Intracranial Embolism and Thrombosis/*etiology ; Nephrotic Syndrome/*complications ; Protein S Deficiency/*complications

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

Acute Disease ; Adult ; Female ; Humans ; Mesenteric Ischemia ; etiology ; surgery ; Pregnancy ; Pregnancy Complications ; surgery ; Protein S Deficiency ; complications ; Remission Induction

The prevalences of deficiencies in antithrombin III (AT III), protein C (PC), protein S (PS) and in the activated protein C (APC) resistance in the thrombotic population of the Trakya region, Turkey were investigated. 37 patients with venous thrombosis (VT) and 17 patients with arterial thrombosis (ArT) were included in this study. The mean ages of the patients with VT and ArT were 46 years (range 20-70) and 38 years (range 32-40), respectively. The activity of AT III was measured by commercially available immuno-turbidimetric assay. The activities of PC and PS were determined by coagulometric assay. The APC resistance was measured using a modified APTT-based clotting assay. Among the VT patients, there were 2 cases (5.4%) with AT III, 5 (13.51%) with PC deficiency, 5 (13.51%) with PS deficiency and 2 (5.4%) with APC resistance. In the ArT patient group, there was 1 patient (5.88%) with AT III, 3 (17.64%) with PC deficiency, 1 (5.88%) with PS deficiency and no APC resistant patients, while there was one (2.08%) with PC deficiency and one (2.08%) with APC resistance in the control group (49 persons, mean age 41 years). The relative risk of thrombosis (odds ratio) was 1.7 in the deficiency of PC and 5.6 in the deficiency of PS. The data presented suggests that the prevalences of AT III, PC and PS deficiencies causing thrombophilia in the Trakya region of Turkey are higher than in other reported studies while the APC resistance is lower than in others. Further studies including more patients would be required to clarify these discrepancies.
Activated Protein C Resistance/complications ; Adult ; Antithrombin III Deficiency/complications ; Human ; Middle Age ; Prevalence ; Protein C Deficiency/complications ; Protein S Deficiency/complications ; Risk Factors ; Thrombophilia/epidemiology* ; Thrombosis/etiology ; Turkey/epidemiology

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

Protein S deficiency is a rare blood disorder associated with an increased risk of thrombosis. Only a few cases of arterial thrombosis of digestive tract have been noted. We report a case of celiac arterial thrombosis and splenic infarction in 46-year-old male with protein S deficiency. Abdominal computed tomography and angiography revealed thrombotic obstruction of the proximal celiac and common hepatic artery with splenic infarction. His total and free antigen of protein S were normal, however, the activity of protein S was low. Percutaneous transluminal angioplasty was performed to revascularise celiac and common hepatic artery.
*Celiac Artery/radiography ; Humans ; Male ; Middle Aged ; Protein S Deficiency/*complications/genetics ; Splenic Infarction/etiology/*radiography ; Thrombosis/etiology/*radiography ; Tomography, Spiral Computed

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be an aberrant outcome of acute pulmonary thromboembolism, due to inadequate thrombus dissolution. However, the mechanism of thrombi dissolution failure remains unclear. With respect to inherited thrombophilia, the co-occurrence of natural anticoagulant deficiencies with CTEPH was found to be rare. Pulmonary thromboendarterectomy (PTE) is a potentially curative surgical procedure for CTEPH, but it is associated with considerable mortality due to postoperative complications, such as reperfusion pulmonary edema and right heart failure. The postoperative course after PTE poses a unique series of ventilatory care and hemodynamic management challenges. We present the case of a 42-year-old woman with unilateral CTEPH combined with thrombophilia (Protein S deficiency). Successful PTE was followed by independent lung ventilation with unilateral nitric oxide (NO) inhalation, which resulted in functional improvement without postoperative complications.
Adult ; Endarterectomy* ; Female ; Heart Failure ; Hemodynamics ; Humans ; Hypertension, Pulmonary* ; Inhalation ; Lung ; Mortality ; Nitric Oxide ; Postoperative Complications ; Protein S Deficiency ; Pulmonary Edema ; Pulmonary Embolism ; Reperfusion ; Thrombophilia ; Thrombosis ; Ventilation

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.
Adult ; Anticoagulants/therapeutic use ; Base Sequence ; Blood Proteins/*genetics ; Codon, Terminator ; Exons ; Humans ; Male ; Mesenteric Veins/radiography ; Polymorphism, Restriction Fragment Length ; Portal Vein/radiography ; Protein S Deficiency/complications/*diagnosis ; Sequence Analysis, DNA ; Splenic Vein/radiography ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/drug therapy/etiology