Elena Lafoz

Occult cancer in patients with deep venous thrombosis. A systematic approach

The authors prospectively studied 113 consecutive patients with deep venous thrombosis of the lower extremities to determine the most appropriate workup study for searching for a hidden cancer. After a careful physical examination, the following routine tests were performed: erythrocyte sedimentation rate (ESR), whole blood counts, biochemistry, carcinoembryonic antigen (CEA) levels, chest radiograph, upper gastrointestinal endoscopy, abdominal ultrasound and computed tomography (CT) scan. If a malignant lesion was suspected, further appropriate studies were performed. After discharge, periodic follow‐up was performed on all patients in the outpatient clinic. A malignant neoplasm was detected in 12 patients. Of these 12 patients, six were asymptomatic with the exception of experiencing thrombophlebitis. Cancer was found more commonly in patients with idiopathic deep vein thrombosis (DVT) (7 of 31 versus 5 of 82 patients with secondary DVT; P = 0.012), and in those patients with abnormal lactic dehydrogenase (LDH) levels (6 of 23 versus 6 of 90; P = 0.007). Abnormal CEA levels allowed diagnosis of two cases of colonic cancer (on colonoscopy). Both ultrasound and CT scan of the abdomen showed two cases of urinary bladder carcinoma at a very early stage. Furthermore, two cases of adenomatous polyps in colon were found, a condition considered by most authors to be a colorectal cancer precursor. In addition, there were five patients with large benign pelvic tumors, and two patients with absent inferior vena cava. The most striking finding was that some cases of cancer were at a very early stage. It was concluded that blood cell counts, LDH, CEA, chest radiograph, and abdominal ultrasonography (or CT scan) should be routinely performed on all patients with deep venous thrombosis (particularly those with idiopathic DVT). Malignancy would not have been recognized in some patients if these tests had not been performed.

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

SummaryA 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.

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, Fishers 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.

Heparin-Related Osteoporosis in Rats

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.

Comparative Study on the Antithrombotic Efficacy of Four Low-Molecular-Weight Heparins in Three Different Models of Experimental Venous Thrombosis

In a randomized, blind study, both the antithrombotic efficacy (reduction of thrombus weight) and potency (anti-Xa activity) of several commercially available low-molecular-weight heparins (LMWHs) were compared with those of unfractioned heparin (UFH) and placebo. Three different thrombogenic challenges were used: venous thrombosis was induced by direct endothelial damage in 60 New Zealand rabbits (group I), intracarotid injection of bovine thrombin in an additional series of 60 rabbits (group II), or after inferior-vena-cava ligature in 60 Wistar rats (group III). The drugs were administered subcutaneously 2 h before surgery in a blind fashion. The doses recommended for clinical practice were used (adjusted by body weight), except in group II animals, in whom doses were doubled. No differences were found between UFH and most LMWHs in terms of reduction of thrombus weight in group I animals. But UFH showed a weaker antithrombotic efficacy in the other two models. Similarly, one of the LMWHs used (Clexane) proved to be not as effective as the remainder. However, only clinical studies will provide enough information to verify these differences. Additionally, our findings confirm that the antithrombotic efficacy of a given drug differs according to the stimulus used to induce venous thrombosis.

Preoperative Platelet Count and Postoperative Blood Loss in Patients Undergoing Hip Surgery: An Inverse Correlation

In a previous study we tried to assess the clinical usefulness of platelet count (PlC) to confirm whether postoperative pulmonary embolism could be suspected early. Unexpectedly, the 19 patients who subsequently developed pulmonary embolism had significantly lower mean PlC levels even before surgery. In an attempt to discover whether the preoperative PlC levels were associated with a different incidence of postoperative blood loss, we decided to retrospectively study the relationship between preoperative PlC levels and the consequences of blood loss. There were 459 consecutive patients undergoing hip surgery. After excluding 5 patients who died during the first 3 postoperative days, and 16 patients who bled from a definitive anatomic site, there were 438 patients. Blood loss was considered to be excessive when two or more of the following conditions were present: (1) total transfusion requirements exceeding 1,000 ml whole blood or 2 units of packed red cells; (2) a drop in hemoglobin level of 5 g/dl or more, and (3) a hemoglobin level below 8 g/dl at any moment during the first 8 postoperative days. Blood loss was considered to be excessive in 91 patients. Preoperative PlC levels were significantly lower in these patients as compared to patients without the condition (204 +/- 52 vs. 236 +/- 79 x 10(9) liter-1; p = 0.0002). When patients were classified according to the quartiles of preoperative PlC, the odds ratio of developing excessive blood loss was 0.69 (95% CI: 0.38-1.26) in patients in the second quartile; 0.57 (95% CI: 0.30-1.06) in the third quartile, and 0.27 (95% CI: 0.13-0.57) in patients in the highest quartile. After adjusting for age, sex, type of surgery and type of prophylaxis, the preoperative PlC levels maintained a statistically significant inverse correlation with postoperative blood loss.

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.

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.