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Biomedical subjects

A W Broekmans

Publications and source records attributed to A W Broekmans.

At least 19 recordsLinked to original sources
PubMed1990

Interaction of the combined medication with the new low-molecular-weight heparinoid Lomoparan (Org 10172) and acenocoumarol.

A high intravenous dose of the low-molecular-weight heparinoid Lomoparan (Org 10172) was administered to 6 healthy males in a steady state of anticoagulation (Thrombotest) by acenocoumarol. Prothrombin time, activated partial thromboplastin time and Stypven time were prolonged to a degree which was greater than that expected on the base of the summation of the effects by each drug alone. This effect was observed for a period of up to 1 h. The Thrombotest was affected for up to 5 h after the intravenous administration of Org 10172, therefore it is deemed unsuitable for monitoring the combined effects of these two anticoagulants during this period. Acenocoumarol did not affect the pharmacokinetic parameters of Org 10172 with the exception of a slight reduction of the clearance of plasma anti-Xa activity.

Acenocoumarol↗
PubMed1989

Diagnosis and treatment of homozygous protein C deficiency. Report of the Working Party on Homozygous Protein C Deficiency of the Subcommittee on Protein C and Protein S, International Committee on Thrombosis and Haemostasis.

This report summarizes the documented cases of homozygous protein C deficiency in the United States and Europe. Procedures for diagnosing and treating this disorder (both initially and over the long term) have been compiled by a working party on homozygous protein C deficiency of the Subcommittee on Protein C of the International Committee on Thrombosis and Haemostasis. Homozygous protein C deficiency is an autosomal recessive disorder that usually manifests itself by purpura fulminans and, less commonly, by massive large vein thrombosis; severe diffuse intravascular coagulation also develops in these infants, and there is evidence of intrauterine thrombosis. For confirmation of homozygous protein C deficiency in a neonate with purpura fulminans or massive venous thrombosis, the infant should have undetectable protein C activity and both parents should be heterozygous for protein C deficiency. At the onset of symptoms, the initial treatment should be plasma (8 to 12 ml/kg every 12 hours) until all lesions have healed. Two modalities for long-term treatment are accepted as useful in these children: oral anticoagulant therapy or protein C replacement (fresh frozen plasma or prothrombin complex concentrate). Liver transplantation has been performed in only one child, with success. Oral anticoagulation (vitamin K antagonists, maintaining the prothrombin time from one and one-half to two times control values or at the International Normalized Ratio of 2.5 to 4.4) is our recommendation of choice for long-term treatment. With appropriate care, these children are able to be free of coagulopathy and live relatively normal lives.

Anticoagulants↗
PubMed1988

Hemostatic enzyme generation in the blood of patients with hereditary protein C deficiency.

The presence of hereditary protein C deficiency has been shown to predispose patients to the development of venous thrombosis. We used radioimmunoassays for the protein C activation peptide (PCP) and the prothrombin fragment F1 + 2 to quantitate the extent of in vivo activation of protein C by thrombin-thrombomodulin and prothrombin by factor Xa, respectively, in the blood of individuals with this clinical disorder. A total of 46 protein C deficient subjects from 18 kindreds were studied. In 23 nonanticoagulated patients with an isolated deficiency of protein C, the mean level of PCP was substantially reduced while the mean concentration of F1 + 2 was significantly elevated as compared with normal controls (1.10 pmol/L v 1.78 pmol/L, P less than .0005 and 2.54 nmol/L v 1.51 nmol/L, P less than .0005, respectively). The metabolic behavior of 131I-F1 + 2 was found to be similar in protein C deficient patients and normal individuals. However, we were unable to establish a significant correlation between decreased PCP levels and increased F1 + 2 measurements in these 23 patients. This study demonstrates that heterozygous protein C deficient individuals with equivalent plasma levels of the zymogen may have markedly different biochemical profiles when assay techniques are used that quantitate the in vivo activity of the coagulation system. Six individuals from three pedigrees were identified as having combined deficiencies of protein C and either antithrombin III or protein S; the genetic basis for the combined deficiency state was determined in two of the kindreds. Finally we observed that hemostatic system activity as measured by the PCP and F1 + 2 assays is markedly suppressed in protein C deficient patients who are chronically anticoagulated with coumarin derivatives.

Anticoagulants↗
PubMed1987

Treatment of hereditary protein C deficiency with stanozolol.

Five type I protein C deficient male patients received 5 mg stanozolol b.i.d. during 4 weeks. After four weeks of treatment plasma protein C activity increased from 0.42 to 0.74 U/ml and protein C antigen from 0.49 to 0.75 U/ml. This approximately 1.6 fold increase in plasma protein C was accompanied by an increase in factor II antigen (1.5 fold), factor V activity (1.6 fold), factor X antigen (1.1 fold), antithrombin III antigen (1.3 fold) and heparin cofactor II antigen (1.5 fold), while the concentration of factor VII, factor VIII, and factor IX activity, and of protein S antigen remained unchanged. Prothrombin fragment F1+2, measured in two patients, increased 1.3 fold. In addition to its effect on procoagulant and anticoagulant factors stanozolol had profibrinolytic effects, reflected in an increase in tPA activity and in the concentration of plasminogen. These data indicate that in type I protein C deficient patients stanozolol increases the concentrations of both procoagulant and anticoagulant factors and favours fibrinolysis. The efficacy of stanozolol in preventing thrombotic disease in type I protein C deficient patients, however, remains to be established. During the four weeks of stanozolol treatment no thrombotic manifestations were observed in the protein C deficient patients.

Administration, Oral↗
PubMed1987

Mesenteric vein thrombosis as presenting manifestation of hereditary protein S deficiency.

Protein S deficiency is inherited as an autosomal dominant trait. Heterozygotes with a reduction of 50% in the plasma protein S concentration are at risk for the development of venous thromboembolism, often occurring at an early age without an apparent cause. In the majority of the patients thrombosis is restricted to the superficial or deep venous system of the legs. In this case report we describe the presence of mesenteric vein thrombosis in a 30-yr-old man with hereditary protein S deficiency. In his family protein S deficiency was also recognized in his mother, brother, and niece. Both his mother and brother had a history of thrombotic disease.

Adult↗
PubMed1987

Hereditary protein S deficiency: clinical manifestations.

To analyze the clinical manifestations of protein S deficiency, we evaluated 136 members of 12 families with the disorder. Seventy-one persons were found to be heterozygous for protein S deficiency, which is inherited as an autosomal dominant trait. Venous thrombotic events occurred in 39 patients (55%) and were recurrent in 77%. Most symptomatic patients had various combinations of deep venous thrombosis (74%), superficial thrombophlebitis (72%), and pulmonary embolism (38%), either in succession or simultaneously. On five occasions thrombosis was found at unusual sites, like the axillary, mesenteric, and cerebral veins. The age at the first thrombotic event ranged from 15 to 68 years (mean, 28 years), and at age 35 the probability to be still free of thrombosis was only 32%. Fifty-six percent of the thrombotic events were not preceded by a precipitating condition. In these respects protein S deficiency is similar to protein C deficiency.

Adolescent↗
PubMed1986

Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency.

An elderly woman who had been receiving long-term oral anticoagulant therapy developed skin and subcutaneous fat necrosis on five repeated occasions of extreme hypocoagulability, associated with coinciding periods of congestive cardiac failure. In each episode, the skin necrosis developed within days after the prothrombin time (as determined with Thrombotest) exceeded 200 s (International Normalized Ratio greater than 5.4). Widespread thrombosis in the subcutaneous vasculature and interstitial bleeding, as observed in a skin biopsy specimen, were consistent with a diagnosis of coumarin necrosis. On two occasions, an acquired functional protein C deficiency was present. It is hypothesized that an imbalance between anticoagulant and procoagulant vitamin K-dependent factors contributed to the pathogenesis of coumarin-induced skin necrosis. This imbalance was related to repeated periods of congestive heart failure.

Biopsy↗
PubMed1985

Hereditary protein S deficiency and venous thrombo-embolism. A study in three Dutch families.

Protein S, a vitamin K-dependent coagulation factor, is involved in the regulation of the anticoagulant activity of activated protein C. Using an immunoradiometric assay for total protein S in plasma we identified 14 patients (7 male and 7 female) in three unrelated Dutch families as fulfilling the criteria for an isolated protein S deficiency. In 9 patients who were not receiving oral anticoagulant treatment the mean total protein S antigen concentration was 0.50 +/- 0.08 U/ml (+/- S.D.) and the calculated free protein S concentration was 0.15 +/- 0.01 U/ml (+/- S.D.). In the five patients who were on oral anticoagulant treatment the mean total protein S antigen was 0.23 +/- 0.05 U/ml (+/- S.D.). Seven of the 14 patients had a history of venous thromboembolism occurring at a mean age of 25 years and often without an apparent cause. Protein S deficiency is inherited as an autosomal dominant trait.

Adolescent↗