Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin.

Intravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism. Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin, but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease. Certainly, long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans. This study aimed to compare the efficacy and safety of unfractionated (UF) heparin with that of a low molecular weight heparin (Fragmin, Kabi Pharmacia) in the prevention of recurrent deep venous thrombosis (DVT) and pulmonary embolism (PE) in a consecutive series of patients with contraindications to coumarin therapy. The patients comprised 40 men and 40 women, aged between 19 and 92 years (mean age, 68 years). They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital. All patients had at least one of the following conditions: recent blood loss (either spontaneous or during admission while receiving heparin therapy); active gastroduodenal ulcer disease; psychological or physical inability or unwillingness to understand and accept the need for regular laboratory monitoring during coumarin treatment; chronic alcoholism; dementia; pregnancy; recent neurosurgery, and pericardial effusion; or were over 80 years of age. They were randomly allocated to receive either UF heparin, 10,000 IU s.c. b.d., or Fragmin, 5000 IU anti-Factor Xa s.c. b.d., for a period of 3-6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary embolism in patients with upper extremity DVT associated to venous central lines--a prospective study.

We performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient. Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not. Six points of clinical information were recorded on entering in the study, and then compared with the scintigraphic findings: age, sex, the underlying disease, the catheter material, the character of the infusate, and the duration of cannulation. Thirteen patients were considered to have PE. Sixty-six patients were finally classified as having a normal lung scan, and 7 patients were excluded from the study (because of indeterminate lung scan 6; because of femoropopliteal thrombosis simultaneously present 1). Two out of the 13 patients with PE subsequently died because of recurrent, massive embolism, despite adequate heparin therapy. PE was more commonly present in patients with polyvinyle chloride or polyethylene catheters (10/38, 26%) as compared to patients with either polyurethane or siliconized catheters (3/41, 7%; p < 0.05, Chi-Square test; Odds Ratio = 4.52, 95% CI 1.01-23.07). We conclude that PE is not a rare event in these patients, and it may be life-threatening even despite adequate heparin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet count, antiplatelet therapy and pulmonary embolism--a prospective study in patients with hip surgery.

Pulmonary embolism (PE) is a serious complication following hip surgery. Trials of antiplatelet thromboprophylaxis indicated a substantial reduction in PE rate, and we prospectively studied the effect of a combination of low-dose heparin and two different antiplatelets. Furthermore, our experience in previous studies suggested that platelet count (PC) levels could be useful to reliably suspect PE at a very early stage, and we prospectively tried to confirm our previous findings. Ours is a prospective study in 459 consecutive patients operated on because of hip fracture (265) or elective hip replacement (194), aimed to determine: 1) whether the benefits of antiplatelets plus heparin on PE outweigh the risks; 2) to assess the clinical usefulness of PC monitoring in these patients, so as to confirm whether PE could be recognized early. It was a prospective, randomized, double-blind study. All patients received unfractioned heparin (7500 IU sc twice daily, starting 2 h before operation). In addition, they received aspirin (200 mg thrice daily, with meals), Triflusal (300 mg thrice daily, with meals), or placebo. Real time B-mode ultrasonography (US) was performed on all patients on the 8-9th day after surgery. Venography was performed in patients with normal US, if clinical symptoms suggested venous thrombosis. Twelve out of the 459 patients (2.6%) had to discontinue prophylaxis, because of major bleeding (6 patients), or gastric intolerance (6 patients). There were no significant differences between groups in either deep vein thrombosis (26 patients (18%) with aspirin, 18 (12%) with Triflusal, 26 (17%) with placebo), or PE development (7 patients (5%) with aspirin, 3 (2%) with Triflusal, 8 (5%) taking placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet count and venous thromboembolism. A useful test for suspected pulmonary embolism.

We have previously reported that patients with deep vein thrombosis (DVT) and scintigraphic evidence of pulmonary embolism (PE) had a fall in platelet count, as compared with their levels before thrombosis had developed. Otherwise, no changes were found in DVT patients without embolism. We recently conducted a prospective study with a larger series of patients and studied platelet count behavior in 189 consecutive patients with acute venous thromboembolism (VTE) in whom a baseline blood cell count was available (obtained before thromboembolism developed). We found no significant differences in baseline platelet counts between groups. However, at the time of VTE diagnosis the analysis of variance demonstrated that mean platelet count was significantly higher in patients without embolism as compared with PE patients (p less than 0.001). On the other hand, no differences were found between patients with silent PE and those with clinically obvious PE. When patients with postoperative VTE and those with nonpostoperative VTE were analyzed separately, mean platelet count increased only in postoperative DVT patients without embolism (p less than 0.001). In the absence of a previous intervention, DVT did not produce any change in platelet count, while PE significantly reduced platelet number (p less than 0.008). In DVT patients without respiratory symptoms of embolism, we suggest that a lung scan should be performed when platelet count is lower than baseline value. For patients with a higher count, the probability of finding PE is very low, and scintigraphy is not cost-effective.

Upper-extremity deep venous thrombosis and pulmonary embolism. A prospective study.

We prospectively evaluated the prevalence of pulmonary embolism (PE) in 30 consecutive patients with proved deep venous thrombosis (DVT) of the upper extremity. Ten patients (seven male and three female; mean age, 43 years) had primary DVT, and 20 patients (14 male and six female; mean age, 52 years) had catheter-related DVT. Ventilation-perfusion lung scans were routinely performed at the time of hospital admission to all but one patient (one patient was critically ill, and he died four days after DVT diagnosis because of massive PE). Lung scan findings were normal in nine of ten patients with primary DVT, and they were indetermine in the remaining patient. By contrast, perfusion defects were considered highly suggestive of PE in four patients with catheter-related DVT; two patients had indeterminate lung scans, and 13 patients had normal scans. We conclude that PE is not a rare complication in upper extremity DVT, and that patients with catheter-related DVT seem to be at a higher risk.

Occlusive arterial disease as a form of presentation of homocystinuria.

Homocystinuria was first described in 1962. The disease affects several systems including the eyes, skeletal and nervous and vascular systems. We present the case of a 28-year old woman who presented with a severe occlusive arteriopathy. Screening for the most usual causes of arterial disease in young patients was negative, but a study of aminoaciduria and column chromatography confirmed the diagnosis of B6-responsive homocystinuria. Although it was necessary to amputate her left leg, the patient remains asymptomatic 16 months after B6 therapy was started.

Occult thyrotoxicosis in patients with atrial fibrillation and an acute arterial embolism.

Serum total thyroxine, triiodothyronine, and thyrotropin response to thyrotropin-releasing hormone (TRH-TSH test) were measured in 126 consecutive patients admitted with atrial fibrillation: 33 patients with an acute arterial limb embolism (Group I), 31 patients with an acute embolic stroke (Group II), and 62 patients without any arterial occlusion (Group III). A blunted TRH-TSH test, suggestive of thyrotoxicosis, was found in 5 patients in Group I, 8 patients in Group II, and 2 patients in Group III. The diagnosis of hyperthyroidism was confirmed in 8 patients (by repeated TRH-TSH test and scintigraphy): 4 patients in Group I (12.1%) and 4 patients in Group II (12.9%). All of them had a nonvalvular atrial fibrillation. Thyrotoxicosis should not be recognized in 6 of them if TRH-TSH test was not performed, because peripheral hormone levels were normal. Five of these 8 patients with thyrotoxicosis had reversion to sinus rhythm after treatment with carbimazole, either spontaneously or after cardioversion. This outcome prevented prolongation of anticoagulant therapy for an indefinite time.

[Deep venous thrombosis of the upper limb. A prospective study of the central venous catheter as an etiologic factor and clinical and subclinical incidence of pulmonary thromboembolism]. / Trombosis venosa profunda de la extremidad superior. Estudio prospectivo del catéter venoso central como factor etiológico y su incidencia clínica y subclínica de tromboembolismo pulmonar.

The thrombogenicity presented in different types of endovenous catheters and their anomalies are the cause of the development of pulmonary thromboembolism (PTE) in some patients, secondary to deep venous thrombosis (DVT) of the upper limbs. Presentation of a study made on the incidence of PTE in patients with prior history of DVT of the upper limbs. Of the 30 cases of DVT of the upper limbs studied, 20 were directly attributed to catheters. 18 were attached to a central catheter and the other 2 one or two peripheral catheters. 0,32% of DVT of the upper limbs secondary to a central catheter was calculated. Five of the 20 DVT patients (25%) had symptomatic or sub-clinical DVT. Emphasis was placed on the importance of DVT and its intrinsically serious nature and the need for studies on this condition, since it is possible for the patient not to develop the complete symptoms of DVT at the onset, which led to death in one patient. We recommend the establishing of strict norms with regard to the indications for inserting the central catheter and the choice of the correct material, aseptic and non-traumatic insertion, radiological control (essential) of the position of the catheter and its tip, establishing of a protocol for the correct maintenance and a device for controlling thrombotic complications in upper limbs, to ensure rapid treatment and a rapid check of the possibility of DVT by pulmonary gammagraphy during the first 24-48 hours.

[Compression of the iliac vein and occult neoplasm]. / Compresión de la vena ilíaca y neoplasia oculta.

Three cases demonstrating the possible venous system compression by some neoplasias, feigning an nonexistent thrombosis, are presented. Author stands out the fitness of to investigate possible neoplasias in thrombosis without apparent causality.

Role of granulocytes in the development of venous thrombosis in patients with hip fractures.

In a previously reported study we compared the use of a low-molecular-weight heparin (LMWH) and conventional heparin in the thromboprophylaxis of patients with hip fracture. In an attempt to establish additional factors which could aid in predicting the development of deep-venous thrombosis (DVT), we retrospectively studied several clinical and laboratory variables and found that granulocyte count on admission was higher in patients without subsequent postoperative DVT. Forty additional patients were included in a further prospective study in order to validate our previous findings. 38% of patients who developed DVT had a granulocyte count lower than 9,500/microliters, whereas only 18% of those patients with DVT had a count higher than 9,500/microliters. These figures imply a positive predictive value of 38% and a negative predictive value of 82%. We suggest that granulocytes could play a role in the development of DVT and preoperative granulocyte count may be used to detect a high-risk population for DVT after a hip fracture.

Platelet count in acute pulmonary embolism: its relationship to recurrences.

We have prospectively studied a large series of patients with acute venous thromboembolism, trying to correlate pulmonary embolism (PE) recurrences to a number of clinical variables, and platelet count behavior. A baseline lung scan was obtained initially in every patient. Repeated chest X-ray and lung scans were obtained routinely 8 days after heparin onset. The primary trial endpoint was confirmed, clinically apparent recurrent PE; in addition, laboratory evidence of subclinical PE at the repeat scan was also considered. PE recurrences were found in 26/180 patients, and 3 out of these patients died because of massive, recurrent PE. No significant differences were found in age and sex distribution, or in the degree of deep vein thrombosis proximity between patients who did or did not develop recurrences. There were, however, differences between groups in platelet count: No differences were found in baseline counts, but mean values were significantly lower by the 8th day when recurrences had appeared (229 +/- 86 x 10(9) liters-1 versus 314 +/- 129 x 10(9) liters-1; p < 0.005). The sensitivity, specificity, positive predictive value and negative predictive value for platelet count decrease were 52, 71, 21 and 91%, respectively. Thus, platelet count cannot be reliably used for individual cases, but our findings add to the pathophysiological picture of the disease.

Heparin-related osteoporosis in rats. A comparative study between unfractioned heparin and a low-molecular-weight heparin.

In an animal model, the effect of a high dose of conventional heparin (2 IU/g s.c. twice a day) and a low-molecular-weight heparin (LMWH; Fragmin, 1 anti-Xa U/g once a day) was compared with that of placebo on the mineral bone mass in the femur of rats. After 33 days of treatment no differences were found in the weight of the femur. But heparin-treated rats exhibited a lower density (1,249 +/- 0.046 g/ml as compared with that in control rats (p = 0.00007) and also in LMWH-treated rats (p = 0.001). Similarly, statistically significant differences have been found in ash contents. They were higher in control rats than in heparin-treated rats (p = 0.0002), and also slightly higher than in LMWH-treated rats (p = 0.01). Our findings suggest that LMWH may have a lower osteopenic effect than that of conventional heparin.

Recurrent pulmonary embolism in patients treated because of acute venous thromboembolism: a prospective study.

OBJECTIVE: To evaluate the risk of pulmonary embolism (PE) despite adequate heparin therapy in a large series of patients with acute deep venous thrombosis and/or pulmonary embolism. DESIGN: Prospective study. SETTING: University Hospital Germans Trias i Pujol, Badalona, Spain. MATERIALS: 348 patients admitted because of deep venous thrombosis in the lower limbs and/or pulmonary embolism. A baseline lung scan was obtained initially in every patient, whether the original diagnosis was PE or deep vein thrombosis (DVT). Repeat chest X-ray and lung scans were obtained routinely at 8 days of heparin onset. OUTCOME MEASURES: The primary trial endpoint was a finding of confirmed, clinically apparent recurrent PE; in addition, laboratory evidence of subclinical PE at the repeat scan was also considered. RESULTS: PE recurrences were found in 23/348 patients (7%). No significant differences were found in age and sex distribution, or in the degree of DVT proximity between patients who developed and those who did not develop recurrences. Recurrent PE was more commonly found in patients with scintigraphic evidence of PE on admission, irrespectively of the original diagnosis being DVT or PE (18/151 vs. 3/155; p = 0.0005, Fisher's exact test). Recurrences were also more common in patients in whom thrombosis developed in the absence of any known risk factor (10/70 vs. 13/278; p = 0.007). The logistic regression analysis confirmed the statistical significance of these two clinical variables. CONCLUSIONS: Pulmonary embolism despite adequate heparin therapy is not an uncommon event. It appears possible to identify a subgroup of patients at a higher risk, and, modify treatment accordingly.

Predicting pulmonary embolism in postoperative patients with deep venous thrombosis of lower limbs.

Ventilation-perfusion lung scans were done in 70 patients admitted because of an iliofemoral deep vein thrombosis (DVT), and diagnosed by venography. Eighteen items of clinical and laboratory information were measured to predict the presence of lung scan abnormalities consistent with asymptomatic pulmonary embolism. Eighteen patients had perfusion defects in the lung scan that were classified as "high probability of pulmonary embolism", while the lung scan was normal in 32 patients. Patients with an idiopathic DVT were at high risk of pulmonary embolism, but those with a postoperative DVT had a low embolic risk. In patients with a postoperative DVT two factors predicted pulmonary embolism: those patients who developed symptomatic DVT after an operation but had a normal lung scan showed higher platelet counts than their preoperative levels. Conversely, it they developed a pulmonary embolism their platelet count dropped from their preoperative levels.

Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia.

A prospective study has been made of the incidence of changes in transaminase levels, hyperkalaemia and thrombocytopenia in three groups of patients: 89 consecutive patients with venous thrombosis receiving therapeutic heparinization, 49 patients admitted because of hip fracture and receiving prophylactic low-dose conventional heparin, and 43 patients admitted because of hip fracture and randomly allocated to receive low molecular weight heparin. Laboratory measurements were made on admission and 8 days after commencing heparin. Only two patients on high-dose heparin developed thrombocytopenia. Increased transaminases were frequent with conventional heparin (18% and 32% of patients on high-dose heparin developed abnormal AsT and AlT values, respectively compared with 14% and 17% patients on low dose therapy). In contrast, only one patient on low molecular weight heparin developed abnormal AlT activity. Hyperkalaemia was uncommon in patients on any form of heparin therapy, and severe hyperkalaemia occurred in only one patient.

Gastroduodenal ulcer incidence in patients with venous thromboembolism.

The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants.