Deep vein thrombosis and acute cytomegalovirus infection: case report and review of the literature.

We report the case of a 17-year-old girl with constitutional protein C deficiency who developed massive femoral vein and inferior vena cava thrombosis during the course of an acute cytomegalovirus infection. The possible role of cytomegalovirus in the pathophysiology of venous thrombosis is discussed and a review of the literature is made concerning this peculiar association.     

Type II cryoglobulinemia and brain hemorrhage.

By virtue of an understanding of hemostasis and coagulopathy using modern techniques, the exact role of individual serum protein in vascular thrombosis or hemorrhage becomes more apparent. Cryoglobulin causes vasculitude and thrombosis in various vascular beds, but its role in brain hemorrhage is unknown. We encountered a cryoglobulinemic patient to have cryoglobulinemia, hypocomplementia, and cerebellar hemorrhage during a reactivation of cytomegalovirus infection. Because cryoglobulin is harmful to vessel and hemostasis, and often increases nonspecifically in response to incitement, its weight in vascular syndrome must seriously be reviewed. Coagulopathy in a reactivation of latent virus such as cytomegalovirus should be cautioned in older patients.     

Acute cytomegalovirus infection complicated by vascular thrombosis: a case report.

We present a case report of a previously healthy adult with cytomegalovirus infection that was complicated by extensive mesenteric arterial and venous thrombosis. To our knowledge, this is the first reported case of this syndrome in an immunocompetent individual who had no predisposing risk factors for thrombosis, and it demonstrates the propensity for cytomegalovirus to be involved in vascular disease.     

CASE REPORT: Cytomegalovirus infection as a cause of acute portal vein thrombosis

We report on the case of a 31-year-old woman who developed acute portal vein thrombosis during the course of an acute cytomegalovirus (CMV) infection. We suggest a relationship between CMV infection, its endothelial cell-damaging effects and portal vein thrombosis.     

Superior sagittal sinus thrombosis occurring at high altitude associated with protein C deficiency.

A 42-year-old male presented with right-sided weakness, dysphasia and seizures while climbing the French Alps at an approximate altitude of 3,000 m. Imaging studies were consistent with superior sagittal sinus thrombosis with hemorrhage. Laboratory testing for thrombophilic states, 18 days after presentation at our hospital, showed a low protein C level (0.32 U/ml, normal 0.80-1.60 U/ml). A family member was also found to have protein C deficiency without a history of thrombosis. The patient gradually improved and was discharged on warfarin and valproic acid. This is the first reported case of cerebral venous thrombosis in a patient with congenital protein C deficiency who ascended to high altitude. We postulate that the ascent to high altitude represented an additional prothrombotic risk factor to the congenital protein C deficiency leading to cerebral thrombosis.     

Portal thrombosis complicating an acute cytomegalovirus infection in an immunocompetent patient

INTRODUCTION: The cytomegalovirus (CMV) infection is most often asymptomatic. The grave forms concern the immunocompromised patients. We report a new case pf acute CMV hepatitis complicated with portal thrombosis in an immunocompetent patient. EXEGESIS: A 29 year old man has presented a CMV hepatitis proved by the presence of pp65 protein and the viral DNA in serum. This infection was complicated by a portal thrombosis and the evolution was rapidly favourable under anticoagulant treatment. Eleven cases of major thrombosis complicating acute CMV infection in immunocompetent patients were previously reported in the English and French literature. The absence of local and general cause, the remission without anticoagulation, the elevated risk of thrombosis in both HIV and CMV seropositive patients, and in CMV seropositive renal transplant patients suggest a causal relation. Various pathogenic hypotheses were raised: presence of antiphospholipid antibodies, absent in our case, procoagulant phenotype induction of infected endothelial cells, proliferation induction of smooth cells. CONCLUSION: The acute CMV infection can be considered such as a possible cause of major thrombosis.     

Case report: portal vein thrombosis associated with hereditary protein C deficiency: a report of two cases

Protein C deficiency is one of the causes of curable or preventable portal vein thrombosis. We report two patients of portal vein thrombosis associated with hereditary protein C deficiency. The first patient presented with continuous right upper quadrant pain and high fever. The abdominal sonography revealed normal liver parenchyma but portal vein and superior mesenteric vein thrombosis. Based on a 55% (normal 70-140%) plasma protein C level, he was diagnosed as having protein C deficiency. A trace of his family history showed that his elder brother also had protein C deficiency with a 50% plasma C level. Both patients received anticoagulant therapy. The younger brother showed good response. Unfortunately, the elder one suffered from recurrent episodes of variceal bleeding and received a life-saving splenectomy and devascularization. We herein remind clinicians that early screening and therapy are helpful in preventing late complications of protein C deficiency with portal vein thrombosis.     

Acute portal and mesenteric thrombosis: unusual presentation of cytomegalovirus infection

Cytomegalovirus infection is a benign disease in immunocompetent patients. In-vitro and in-vivo studies show that cytomegalovirus may cause arterial and venous thrombosis through different mechanisms. We describe two cases of acute cytomegalovirus infection complicated by portal and mesenteric vein thrombosis leading to intestinal ischemia. Both patients carried the heterozygous prothrombin G20210A mutation. The presence of this unusual complication should be searched for in patients with acute cytomegalovirus infection and abdominal symptoms in order to start early anticoagulation. The necessity for full thrombophilic screening is also pointed out.     

Cerebral sinus thrombosis in a patient with hereditary protein S deficiency: Case report and review of the literature

Summary Hereditary protein S deficiency is an established risk factor for venous thrombosis. The common sites of thrombosis are the deep leg and pelvic veins. We report on a 38-year-old female patient with hereditary protein S deficiency and a previous history of deep leg vein thrombosis, who developed thrombosis of the cerebral straight and superior sagittal sinus while taking oral contraceptives. The diagnosis was established by computerized tomography and carotid angiography. Lysis of the thrombus occurred during heparin treatment. The hereditary nature of protein S deficiency was documented by family studies, since nine additional family members deficient in protein S were identified. Nineteen published cases of cerebral vein thrombosis and a deficiency of either antithrombin III, protein C, or protein S were reviewed. Compared with patients without a deficiency state, the clinical features of cerebral vein thrombosis were similar except for an earlier onset and a positive medical history of venous thromboembolic events in a considerable number of patients.     

Resistance to activated protein C and portal vein thrombosis: two new cases and review of the literature]

INTRODUCTION: Resistance to activated protein C is the most common inherited factor at the origin of deep venous thrombosis. As portal vein thrombosis is rare, causes such as cirrhosis, intra-abdominal infection, primary hepatocellular carcinoma, myeloproliferative disorders or coagulation abnormalities must be investigated. EXEGESIS: We report two cases of portal vein thrombosis associated with resistance to activated protein C. This association is not frequent, as only 12 cases have been reported in the literature. These studies show that resistance to activated protein C was rarely the only factor, as other prothrombotic abnormalities were present in more than 70% of cases. CONCLUSION: Resistance to activated protein C is rarely associated with portal vein thrombosis. When present, other causes should not be overlooked. The potential existence of resistance to activated protein C should be systematically investigated in case of either portal vein thrombosis in patients with personal or familial thrombosis history, association with multiple thrombosis, or when the disease etiology remains unknown.     

Traumatic unilateral renal artery thrombosis and protein C deficiency. A case report

Post traumatic renal artery thrombosis is rarely described in the literature. This pathology can result from stretch injury to inelastic intima of the renal artery, or by the direct flow to the abdomen causing compression injury to the renal artery against the vertebral column. However, the association of this pathology with hematologic diseases (in particular protein C deficit) was never described. We report an observation of a 28-year-old man with an uneventful history who was admitted to the intensive care unit for traumatic head injury associated with post traumatic renal artery thrombosis requiring nephrectomy. The etiologic investigation of this thrombo-embolic complication reveals a protein C deficit. Our patient was improved under treatment. This original observation confirms that post traumatic renal artery thrombosis can be associated with hematologic diseases (in particular protein C deficit).     

Hereditary protein C deficiency and portal-vein thrombosis

Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family history of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported.     

Deficiency of protein C in patients with portal vein thrombosis

Portal vein thrombosis has been considered idiopathic in 50% of cases reported in adults. Protein C deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein C was present. Both cases were very similar, with a history of recurrent episodes of systemic thromboembolic disease, mesenteric venous thrombosis that required intestinal resection and upper gastrointestinal bleeding from gastroesophageal varices. Portal hypertension as well as portal vein thrombosis were demonstrated. The hematologic work-up revealed a deficiency of protein C. Both patients were subjected to the Sugiura procedure, and anticoagulation was instituted thereafter. At the time of surgery, a liver biopsy was performed, which was reported as "normal." Two years and 3 months, respectively, after surgery both patients are in good condition. We conclude that protein C deficiency should be investigated in all cases of portal vein thrombosis, especially in those with a history of thromboembolic disease elsewhere.     

Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial

Tamoxifen reduces breast cancer incidence among healthy women, but is associated with an increased risk of venous thrombosis. We studied the 6 month effects of tamoxifen on venous thrombosis risk factors in women without cancer. One hundred and eleven women at one centre who were participants in a multicentre breast cancer prevention trial were randomized, in double-blind fashion, to receive 20 mg/d of tamoxifen or placebo. The activated protein C (APC) ratio and concentrations of antithrombin, protein C antigen, and total protein S were measured at baseline and 6 months of treatment. None of the factors changed over 6 months in placebo-treated women. Among tamoxifen-treated women, antithrombin and protein S, but not protein C or APC ratio were reduced. Sequential antithrombin concentrations with tamoxifen were 114% and 104% (P = 0.001 compared with placebo). Sequential protein S concentrations with tamoxifen were 18.42 and 17.30 micro g/ml (P = 0.02 compared with placebo). Reductions in antithrombin and protein S were greater in postmenopausal women, but did not differ by other risk factors for venous thrombosis, such as body mass index. Reductions of antithrombin and protein S, but not protein C or APC resistance, might relate to the increased risk of venous thrombosis associated with tamoxifen treatment.     

Asymptomatic homozygous protein C deficiency

We report a family in which 2 homozygotes with similarly very low protein C levels have different clinical symptoms. One had recurrent venous thrombosis starting at the age of 28 years, the other is still asymptomatic at 38 years despite exposure to thrombotic risk factors. Our review of 13 additional cases reveals a highly variable phenotypic expression of homozygous protein C deficiency, which can be subdivided into two groups. In the first group are 8 kindreds in which homozygotes presented at birth with unmeasurable protein C levels and life-threatening thrombosis and 1 kindred in which homozygotes are characterized by very low levels of protein C but delayed onset (10 months of age) of thrombosis. In the second group are 4 kindreds characterized by very low, but measurable, protein C levels in homozygotes who survived beyond the neonatal period into adulthood with histories of moderately severe thrombosis. The present case demonstrates that protein C levels lower than 10% are compatible with a negative history for thrombosis, not only in the neonatal period but also during adulthood, and suggests that in some homozygotes other factors need to interact for full clinical penetrance of the defect.     

TRANSIENT PROTEIN S DEFICIENCY ASSOCIATED WITH CEREBRAL VENOUS THROMBOSIS IN ACTIVE ULCER ATI VE COLITIS

Cerebral venous thrombosis is an uncommon complication of ulcerative colitis. We report the case of a 29-yr-old female with a recent diagnosis of ulcerative colitis who suffered stroke secondary to thrombosis of the veins of Galen and straight sinus. A search for a tiypercoagulahle state revealed a nonfamilial transient protein S deficiency. Possible involvement of C4b-binding protein in this hypercoagulable state is discussed.     

Mycoplasma pneumonia and pulmonary embolism in a child due to acquired prothrombotic factors

We report on a child with Mycoplasma pneumonia, who developed an unexplained new oxygen requirement. He was found to have an ileo-femoral thrombosis and an acute pulmonary embolus, with positive anti-phospholipid antibodies and acquired activated protein C resistance. These are both acquired risk factors for venous thrombosis. He was successfully anti-coagulated and well at follow-up with disappearance of the anti-phospholipid antibodies, and normalization of his activated protein C activity. Children who present with Mycoplasma infections who run an atypical course should be monitored closely for signs of thrombosis. Thrombosis formation should also be considered in those children with deteriorating respiratory status, but little change in radiographical findings. Children found to have developed thrombi should be investigated with a full thrombophilia screen to elicit both congenital and acquired risk factors, and should be anti-coagulated appropriately.     

Enzyme enhancement for the measurement of protein C

Protein C measurement is now a necessary work-up of a patient with thrombosis. We described an enzyme enhancement of Laurell's immunoelectrophoresis for assay of protein C antigen. With this modification, the rockets are well defined and easily visualized and the sensitivity of the assay increased (2.5%). Samples with low protein C antigen are easily assayed.     

Two-dimensional echocardiographic diagnosis of tricuspid valve noninfective endocarditis due to protein C deficiency (lesion mimicking tricuspid valve myxoma)

Noninfective endocarditis may develop on heart valves in a wide variety of clinical conditions. Various events have been cited as possible etiologic factors. These lesions are clinically important because the vegetations frequently embolize and cause arterial obstruction and tissue infarction. Previously, the diagnosis of the disease had been made only at autopsies. Only a single case has been reported to have been diagnosed clinically in childhood. We present a patient with noninfective endocarditis, urgently operated on with the presumptive echocardiographic diagnosis of tricuspid valve myxoma, whose protein C level was found to be very low. It's known that in patients with homozygous congenital protein C deficiency venous thrombosis may develop. We think that the etiologic factor of the thrombosis on the tricuspid valve in the case presented is congenital protein C deficiency. With this case study we further emphasize the specific role of two-dimensional echocardiography in the diagnosis of noninfective endocarditis and recommend that protein C deficiency be investigated as an etiologic factor.     

Portal vein thrombosis with ruptured oesophageal varices as presenting manifestation of hereditary protein C deficiency.

The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son and one nephew who were asymptomatic. Hereditary protein C deficiency should be considered in patients with portal hypertension due to portal vein thrombosis.