Oral Contraceptives, Antithrombin-Iii Activity, and Postoperative Deep-Vein Thrombosis

S, Sagar; Thomas, Duncan P.; Stamatakis, J. D.; Vv, Kakkar

doi:10.1016/s0140-6736(76)90296-8

Cited by 140 publications

(39 citation statements)

References 8 publications

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“…It is clear that antithrombin III reductions in the hereditary state or induced by oral contraceptives of the magnitude noted in this study can predispose patients to venous thrombosis (5,8). Because apalcillin also produces a mild functional platelet defect, perhaps the tendency toward thrombosis might be counteracted.…”

Section: Resultsmentioning

confidence: 75%

Effects of apalcillin on platelet function in normal volunteers

Gentry¹,

Wood²,

Natelson³

1985

Antimicrob Agents Chemother

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We investigated the effects of apalcillin on blood coagulation and platelet function. The drug was administered to 21 human volunteers in daily intravenous doses of 75, 150, and 225 mg/kg. These doses evoked abnormalities in platelet aggregation similar to those found with piperacillin and mezlocillin and less striking than those produced by carbenicillin and ticarcillin. Plasma coagulation as measured by prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration was not affected. There were consistent and major reductions in plasma antithrombin III activity, particularly at the two higher dose levels. Of 21 patients, 7 (33%) also manifested maculopapular skin rashes which resolved after discontinuation of the drug.Penicillin and its semisynthetic antibiotic derivatives may affect hemostasis by causing a time-and dose-related defect in platelet aggregation (3, 9). The resultant platelet functional abnormality is most easily demonstrated in vitro by reduced aggregation to an ADP stimulus and in vivo by prolongation of the template bleeding time (7). Severity of the hemostatic defect is variable, however, and seems more predictable and profound with carbenicillin and ticarcillin, for example, than with piperacillin, mezlocillin, and ampicillin (2-4, 6, 7, 9). Apalcillin is a new semisynthetic penicillin with an extended antibacterial spectrum. It is structurally related to ampicillin. We administered apalcillin to normal human volunteers to assess its effects on hemostasis.MATERIALS AND METHODS Subjects. A total of 21 normal, healthy human volunteers (15 males, 6 females), ranging in age from 22 to 34 years (mean age, 24 years), entered Medical Center Del Oro Hospital in Houston, Texas, where the study was done. Initial evaluation included a history and physical examination to exclude anyone with evidence of peptic ulcer disease, gastrointestinal bleeding, renal disease, or penicillin allergy. Also performed were complete blood count, blood chemistries, urinalysis, electrocardiogram, and stool examination for occult blood. Each volunteer provided informed consent.Drug administration. Apalcillin (Wyeth Laboratories, Philadelphia, Pa.) was reconstituted to the desired concentration and then diluted in 100 ml of 5% dextrose in water and infused intravenously every 8 h. The volunteers were divided into three groups of seven. The volunteers received apalcillin daily at a dose of 75 (group A), 150 (group B), or 225 (group C) mg/kg for a 7-day period.Coagulation studies. Blood coagulation and platelet function were evaluated upon initiation of the study, and the evaluation was repeated on days 4, 7, and 14 after the start of antibiotic infusion. Platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, and template bleeding time (Simplate; General Diagnostics, Div. Warner-Lambert Co., Morris Plains, N.J.) followed standard methodology (7). Platelet aggregation was measured in a PAP-3 aggregometer (Bio/Data Corp., Horsham, Pa.). Aggregation was induce...

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Section: Resultsmentioning

confidence: 75%

Effects of apalcillin on platelet function in normal volunteers

Gentry¹,

Wood²,

Natelson³

1985

Antimicrob Agents Chemother

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“…There is an estimated 12 percent incidence of thrombophlebitis in women during the course of pregnancy or following delivery. 6 We have no indication that this patient had hypercoagulability during her pregnancy other than her arterial thrombus. I must wonder whether the fact that two of these events occurred during pregnancy contributed to the basic problem.…”

Section: Differential Diagnosis William Robinson MDmentioning

confidence: 85%

“…Recent studies suggest that this is the result of a decrease in the levels of AT III, but the mechanism whereby this occurs has not been defined. 6 The second situation in which it occurs is after surgery.…”

Section: Differential Diagnosis William Robinson MDmentioning

confidence: 99%

Clinicopathologic Conference

et al. 1982

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A 23-year-old, right-handed female was admitted to the King Faisal Specialist Hospital and Research Centre because of inability to talk.Seven years prior to admission, she had sudden inability to talk, lasting two days. She was four months pregnant at that time and went into spontaneous abortion. Subsequently, the patient had three, normal, uneventful pregnancies. Eleven months prior to this admission she had another sudden, one week episode of inability to talk associated with awkwardness on the right side, from which she recovered. She was eight months pregnant and delivered a normal child one month later. Six months following delivery, she again developed sudden onset of inability to talk, associated with right-sided awkwardness. This time, she did not improve and was referred to us for investigation, three months later. The patient gave no previous history of serious illnesses. She was never on contraceptive pills. Her father and mother were distant cousins. There was no family history of a similar condition.On examination, her blood pressure was 120/70 mmHg in both arms. Carotid and peripheral pulses were normal and no bruits were heard over the neck or supraclavicular regions. Examination of the heart did not reveal any murmurs, and the lungs were clear. Abdominal examination was normal, and no skin lesions were seen. On neurological examination, the patient appeared awake and alert. She could say a few words but was unable to understand complex commands, name objects, or repeat after the examiner. Her pupils were equal and reactive and her discs were sharp. She had a questionable right homonymous hemianopsia. A right seventh cranial nerve weakness was noted. No gross weakness was detected on the right, but she was unable to perform fine movement. Stretch reflexes were slightly brisk on the right. Sensory examination was uninterpretable.Complete blood count (CBC) showed a hemoglobin of 12.8 g/dl and a white blood count of 5800/cmm. Platelet count was 380,000/cmm with a sedimentation rate of six millimeters during the first hour. Rapid plasma reagin (RPA) test results were negative and antinuclear antibody test results were negative at 1: 10 dilution. Sickling test results were positive but hemoglobin electrophoresis showed hemoglobin A, 58.6%, hemoglobin S 38.7%, and hemoglobin A 2 2.7%. SMAC-20™ blood analysis was within normal limits. Cerebrospinal fluid examination and urinalysis were normal.Chest radiograph and electrocardiogram were normal. Echocardiogram was normal. Radiograph of the knees was normal.Computed tomographic (CT) scan of the head revealed multiple areas of encephalomalacia in the left hemisphere. Digital subtraction angiography (DSA) showed normal internal carotid and vertebral arteries. Cerebral angiogram showed occlusion of the anterior ascending branches of the left middle cerebral artery. Hemostatic function studies were performed. Philip Weaver MD:This lady had three normal sets of radiographs, a chest study, a skull radiographic examination, and radiographs of her knees. The reason...

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“…Westermark's sign of hyperlucency in an area of oligaemia has been reported positive in between 15 and 71 % of cases. Parenchymal lung consolidation and atelectasis occur in 47%, diaphragmatic elevation in 40%' pleural effusion in 28% of cases.I7 Pulmonary infarction occurs in about one third of cases of pulmonary embolisation.…”

Section: Chest X-raymentioning

confidence: 98%

Pulmonary embolism

Price

1976

Anaesthesia

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Oral Contraceptives, Antithrombin-Iii Activity, and Postoperative Deep-Vein Thrombosis

Cited by 140 publications

References 8 publications

Effects of apalcillin on platelet function in normal volunteers

Effects of apalcillin on platelet function in normal volunteers

Clinicopathologic Conference

Pulmonary embolism

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