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A letter to the editor discussing the use of hydroxychloroquine in patients with surfactant protein C deficiency is presented.

The article presents a review article looking at the Budd-Chiari Syndrome. The syndrome is a group of disorders characterized by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the inferior vena cava, or the right atrium. According to the article, doppler ultrasonography of the liver is the technique of choice for initial investigation when the Budd-Chiari syndrome is suspected. The article discusses the medical management of the Budd-Chiari syndrome, which consists of efforts to control the further development of ascites, the use of anticoagulation therapy to prevent the further extension of the venous thrombosis, and the treatment of underlying causes.

An 18-year-old woman presented to the hospital with hepatomegaly and ascites. The patient reported she had been in good health until she began taking birth control pills. She discontinued the contraceptives after four days due to bloating. Prior to admission the patient had been gaining weight. Physical examination showed a distended abdomen which was attributed to ascites. The work up on the patient is described and test results are provided. The preliminary diagnosis was protein C deficiency or Budd-Chairi syndrome which is a genetic defect. The patient received a liver transplant and her protein level increased to 82 percent just one week after the surgery.

The article focuses on familial thrombosis and resistance to activated protein C in a family in which four of five children are homozygous for the Arg-to-Gln mutation in the factor V gene. The oldest son was hospitalized at the age of 18 years for treatment of venographically confirmed deep-vein thrombosis of the right leg after an injury to this extremity. Another son had a spontaneous deep-vein thrombosis of the left leg at the age of 23 years that was confirmed by venography. He was hospitalized and treated with heparin and then with warfarin for two years.

Background: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes. Methods: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later. Results: The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, P = 0.011), a larger immediate increase in the diameter of the lumen (1.72 ±0.46 vs. 1.23 ±0.48 mm, P<0.001), and a larger luminal diameter immediately after the procedure (2.49 ±0.43 vs. 1.99 ±0.47 mm, P<0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 ±0.60 vs. 1.56 ±0.65 mm, P = 0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, P = 0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 percent of the patients in the stent group and 76.2 percent of those in the angioplasty group (P = 0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 percent vs. 15.4 percent, P = 0.06). Conclusions: In selected patients, placement of an intracoronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion. (N Engl J Med 1994;331:496-501.) [ABSTRACT FROM AUTHOR]

Background: Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased frequency of thrombophilic mutations is not known., Methods: We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The women were tested several days after delivery for the mutation of guanine to adenine at nucleotide 1691 [corrected] in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies., Results: The mutation at nucleotide 1691 [corrected] in the factor V gene was detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies (20 percent and 6 percent, respectively; P=0.003). Twenty-four women with complications, as compared with nine women without complications, were homozygous for the C677T mutation in the gene encoding methylenetetrahydrofolate reductase (22 percent and 8 percent, respectively; P=0.005). The G20210A mutation in the prothrombin gene was found in 11 women with complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03). Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women with normal pregnancies (52 percent and 17 percent, respectively; P<0.001). Deficiency of protein S, protein C, or antithrombin III or anticardiolipin antibodies were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (13 percent and 1 percent, respectively; P<0.001)., Conclusions: Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.

Background: Previous studies have suggested that hyperhomocysteinemia may be a risk factor for venous thrombosis. To assess the risk of venous thrombosis associated with hyperhomocysteinemia, we studied plasma homocysteine levels in patients with a first episode of deep-vein thrombosis and in normal control subjects., Methods: We measured plasma homocysteine levels in 269 patients with a first, objectively diagnosed episode of deep-vein thrombosis and in 269 healthy controls matched to the patients according to age and sex. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (18.5 micromol per liter)., Results: Of the 269 patients, 28 (10 percent) had plasma homocysteine levels above the 95th percentile for the controls, as compared with 13 of the controls (matched odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.2). The association between elevated homocysteine levels and venous thrombosis was stronger among women than among men and increased with age. The exclusion of subjects with other established risk factors for thrombosis (e.g., a deficiency of protein C, protein S, or antithrombin; resistance to activated protein C; pregnancy or recent childbirth; or oral-contraceptive use) did not materially affect the risk estimates., Conclusions: High plasma homocysteine levels are a risk factor for deep-vein thrombosis in the general population.

Background: In three families with various forms of venous thrombosis, we observed an apparently inherited poor response to the anticoagulant activated protein C (APC). The condition was due to a deficiency in a previously unrecognized anticoagulant factor that functioned as a cofactor to activated protein C., Methods: We conducted the present study to determine the prevalence of resistance to APC in patients with venous thrombosis. We compared 104 consecutive patients with venous thrombosis confirmed by objective tests with 130 controls. In addition, 211 members of 34 families of persons with resistance to APC were studied. The anticoagulant response to APC was measured with a modified version of the activated partial-thromboplastin time test; the results were expressed as APC ratios., Results: Forty-five percent of patients had a family history of thrombosis. A significant (P < 0.001) difference in APC ratios was observed between the controls and the patients with thrombosis. For 33 percent of patients, the APC ratio was below the 5th percentile of the control values, although the results of the family studies suggested that the prevalence of APC resistance may be even higher (approximately 40 percent) in the patients with thrombosis. The inherited nature of the defect was confirmed in a majority of cases, and the family studies suggested the mode of inheritance to be autosomal dominant. The thrombosis-free survival of APC-resistant family members was significantly less than that of non-APC-resistant family members., Conclusions: There was a high prevalence of APC resistance among young persons with a history of venous thrombosis, and this resistance appeared to be inherited as an autosomal dominant trait.

Protein C deficiency has been thought to be associated with an increased risk of venous thrombosis. To establish a normal range of values, we used a two-site monoclonal-antibody assay to measure protein C levels in 699 healthy adults. The distribution was log normal; 95 percent of the values ranged from 70 to 140 percent of the overall mean (4.03 micrograms per milliliter). Two subjects had levels more than 3.5 SD below the mean (34 and 50 percent), consistent with heterozygous deficiency. We also screened 4723 other blood donors and found 8 additional unrelated subjects with levels from 33 to 51 percent of normal. Autosomal inheritance of heterozygous protein C deficiency was confirmed in them by a detailed study of four families. Levels from 55 to 65 percent of normal are consistent with either heterozygous deficiency or the lower end of the distribution of normal values, and were found in 79 of 5422 subjects when the two groups were combined. None of the subjects had any history of venous thrombosis. We conclude that heterozygous deficiency of protein C has a prevalence of 1 in 200 to 300, a figure consistent with the known number of homozygous infants recently identified, and that levels consistent with heterozygous deficiency are found in 1 in 60 healthy adults but are not detectably associated with a risk of thrombosis.