Heparin cofactor II in adults and infants with thrombosis and DIC

Heparin cofactor II (HC II) was measured by a chromogenic activity assay in normal preterm infants (gestational age, 28-36 weeks; n = 17; 29% +/- 11.5 [mean +/- 1 SD], range 11-51), normal full-term infants (n = 18; 49% +/- 6.6 [mean +/- 1 SD], range 36-58), and normal adults (n = 38; 101% +/- 14 [mean +/- 1 SD], range 73-130). Normal children attained adult levels at approximately 5 to 7 months of age. The lower values in preterm and term infants most likely reflect immature liver function. Neither adults and children with a history of thrombosis with prior negative evaluation (n = 74), patients with documented protein C and protein S deficiency (n = 4), nor sick infants without evidence of consumptive coagulopathy (n = 15) had significantly lower levels of HC II activity. Infants with disseminated intravascular coagulation (n = 2) had strikingly lower levels of HC II activity.     

Suspected acute deep vein thrombosis in patients with rheumatoid arthritis

Real-time venous ultrasound has replaced phlebography for making the diagnosis of clinically relevant lower extremity DVT. Phlebography is still useful in suspected calf vein thrombosis when an immediate diagnosis is required and in the postoperative patient. A combination of sonography and contrast phlebography is used to sort out the extent of chronic and acute venous changes in patients with chronic deep vein thrombosis.     

Heart failure in patients with deep vein thrombosis

Patients with heart failure (HF) are particularly vulnerable to the development of venous thromboembolism (VTE) and its related complications of pulmonary embolism and right ventricular failure. To improve our understanding of the clinical characteristics, prophylaxis, and initial management of patients with HF and deep vein thrombosis (DVT), we compared 685 patients with a history of HF with 3,890 patients without HF in a prospective registry of 5,451 consecutive patients with ultrasound-confirmed DVT. We excluded 876 patients for whom data regarding HF status were incomplete. Patients with HF had an increased frequency of co-morbid conditions such as neurologic disease including stroke (33% vs 26%, p = 0.0002), acute lung disease including pneumonia (31% vs 15%, p <0.0001), and acute coronary syndrome (11% vs 4%, p <0.0001) contributing to a higher medical acuity than in patients without HF. Furthermore, patients with HF were more likely to have VTE risk factors of immobilization (53% vs 42%, p <0.0001), acute infection (33% vs 27%, p = 0.01), and chronic obstructive pulmonary disease (29% vs 12%, p <0.0001). Patients with and without HF and DVT had a high frequency of recent hospitalization (48% vs 47%, p = 0.96). Fewer than 12 of patients with HF (46%) who subsequently developed DVT received any VTE prophylaxis. In conclusion, the combination of higher medical acuity, increased frequency of VTE risk factors, and low rate of VTE prophylaxis presents a "triple threat" to patients with HF.     

Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer

Journal of Thrombosis and Thrombolysis - After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of...     

Postoperative deep vein thrombosis in patients with colorectal cancer

Deep vein thrombosis (DVT) is reported to be common among patients undergoing surgery for colorectal cancer. This randomized controlled trial was aimed to determine the efficacy of low molecular-weight heparin in the prophylaxis of DVT in this high-risk group and was truncated early in view of an unexpectedly low incidence of DVT. Between March 2002 and January 2004, a total of 99 patients with colorectal cancer - selected for surgery in the lithotomy position - were randomized before surgery to either receive dalteparin or no drug (51 and 48 patients, respectively) during the perioperative period. Duplex ultrasonography was performed before and after the surgery. We also looked for distal venous thrombosis, pulmonary embolism, hemorrhage and any mortality. No episode of DVT occurred in either the drug arm or the observation arm. There was no death following surgery. The incidence of DVT in Indian patients operated for colorectal cancer in the lithotomy position was negligible.     

Splenic vein thrombosis in patients with acute pancreatitis

We performed a retrospective autopsy case-control study to identify clinical characteristics of acute pancreatitis associated with splenic vein thrombosis. Age, sex, spleen weight, presence or absence of gastrointestinal hemorrhage, and pancreatic pseudocyst were not associated with splenic vein thrombosis. Patients with peak serum amylase over 10,000 U/L were at high risk for splenic vein thrombosis. We conclude that, of the factors examined, only the peak serum amylase may be of value in diagnosing splenic vein thrombosis in patients with acute pancreatitis.     

Splenic vein thrombosis in patients with acute pancreatitis

We performed a retrospective autopsy case-control study to identify clinical characteristics of acute pancreatitis associated with splenic vein thrombosis. Age, sex, spleen weight, presence or absence of gastrointestinal hemorrhage, and pancreatic pseudocyst were not associated with splenic vein thrombosis. Patients with peak serum amylase over 10,000 U/L were at high risk for splenic vein thrombosis. We conclude that, of the factors examined, only the peak serum amylase may be of value in diagnosing splenic vein thrombosis in patients with acute pancreatitis.     

Ruling out deep vein thrombosis in patients with superficial vein thrombosis: external validation of the ICARO score

Journal of Thrombosis and Thrombolysis - A clinical score was recently proposed to rule out concomitant DVT in patients with a clinical suspicion of SVT. This study aimed to assess the external...     

Whole blood coagulation assessment using rotation thrombelastogram thromboelastometry in patients with acute deep vein thrombosis

Common tests for the assessment of blood coagulation in the acute phase of deep vein thrombosis are of limited value for the evaluation of the associated hypercoagulability. The new rotation thromboelastometry by rotation thrombelastogram has the potential to provide information on whole blood clot formation and prothrombotic state in patients with acute deep vein thrombosis. Rotation thrombelastogram parameters were evaluated in whole blood of 30 patients with a first episode of acute deep vein thrombosis and 40 healthy controls. The effect of factor VIII and fibrinogen levels on rotation thrombelastogram assays was also assessed in the study population and in a model of blood supplemented by increasing amounts of fibrinogen. All assays performed were consistent with a remarkable hypercoagulable profile in deep vein thrombosis patients as compared with controls. In particular, maximum clot firmness and the area under curve values, which are expected to better correlate with the hypercoagulable state in the acute phase of deep vein thrombosis, were significantly higher in patients than in controls. As expected, fibrinogen was shown to be one of the main determinants of the hypercoagulability in rotation thrombelastogram assays. In a small subset of acute deep vein thrombosis patients, inherited thrombophilia had no influence on rotation thrombelastogram parameters. The new rotation thrombelastogram thromboelastometry is a useful tool to detect acute deep vein thrombosis-related hypercoagulability. Prospective studies are needed to define the potential applications of rotation thrombelastogram in the management of deep vein thrombosis patients.     

Thrombus removal with a temporary vena caval filter in patients with acute proximal deep vein thrombosis

Between September 1999 and January 2001 we performed thrombus removal with the use of a temporary vena caval filter in 11 patients who had acute iliofemoral venous thrombosis. To facilitate thrombus removal, 5 patients initially received catheter-directed thrombolytic therapy (thrombolysis group), and the other 6 received surgical thrombectomy (thrombectomy group). Residual thrombus was confirmed after initial catheter-directed thrombolysis in all patients in the thrombolysis group, and thrombolysis was continued in the ward. Bleeding complications subsequently occurred in 2 patients. In the thrombectomy group, 1 patient had residual thrombus just below the temporary filter, and a permanent vena caval filter was deployed for removal. Another patient had a residual thrombus in the superficial femoral vein, and rethrombectomy was performed. One patient in the thrombectomy group died of pneumonia. All other patients were discharged. There were no deaths from pulmonary thromboembolism in this series. Post-thrombotic syndrome occurred in 2 of the 5 patients in the thrombolysis group (40%) and in 3 of the 6 patients (50%) in the thrombectomy group. We conclude that a temporary vena caval filter is useful for the management of acute proximal deep vein thrombosis, especially when aggressive treatment is required.Presented at the 31st Annual Meeting of the Japanese Society for Cardiovascular Surgery, Yamaguchi, Japan, February 2001.     

Thrombotic disorders of hemostasis in patients with deep vein thrombosis

For 22 months we investigated the hemostatic status of 93 inpatients (44 male, and 49 female, average age 54.6 years) with a phlebographically objectified deep venous thrombosis of the leg or iliac veins. Corresponding blood samples were taken before, during, and after therapy. In 58 (62.4%) patients we found several kinds of disorders of hemostasis. There were deficiencies of the protein C, protein S, factor XII, antithrombin III, and the thrombocytes function. In most cases there was a single acquired deficiency of one of these factors. Only in one patient (1.07%) could we verify an inherited deficiency of factor XII. The most frequent disorder was a protein C deficiency in 32 (34.4%) patients. In 44 (47%) operatively treated patients we had postoperative complications such as rethrombosis, phlegmasia coerulea dolens, or development of skin necrosis during anticoagulant therapy in 12 (27.3%) cases. In 10 (83%) of these patients with complications we had found preoperatively a disorder of hemostasis. The statistical correlation between a preoperatively measured deficiency of the protein C and the relapse of deep vein thrombosis was significant (p=0.0026).Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Ambulatory care for ambulant patients with deep vein thrombosis

A follow-up study is reported on 49 patients with acute deep vein thrombosis (DVT) treated on an ambulatory basis. Venography had shown crural DVT in 27 % and proximal extension in 73 %. The initial treatment consisted of heparin (7,500 U iv, 40,000 U sc), ethylbiscoumacetate (900 mg), phenprocoumon (9 mg), and a ready made compression stocking for the calf. The patients were advised to undertake frequent strolls, the first when leaving the office. Pain, swelling and incapacity for walking vanished within two days. The partial thromboplastintime was prolonged 2.4-times on the first day and the thromboplastintime was in the therapeutic range on the second day already. Until follow-up 4 patients died of other diseases. There was no clinical pulmonary embolism, no secondary hospitalisation and only one new DVT. Of 844 months of patients at risk of recurrence 50 % passed under anticoagulants and 70 % with compression therapy. At an average of 19 months, 82 % of patients were asymptomatic and 45 % showed mild chronic venous insufficiency. In contrast, impaired drainage function (by lightreflectionrheography) was found in 79 % overall and in 100 % after DVT of the proximal veins. The discrepancy is explained by the compliance with compression therapy.     

Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure

Heparin cofactor II (HCII) is a glycoprotein in human plasma which inactivates thrombin rapidly in the presence of heparin or dermatan sulfate. We have developed a functional assay for HCII in which inhibition of thrombin by plasma is determined in the presence of dermatan sulfate. The assay is specific for HCII by the following criteria: (a) under the conditions of the assay, 125I-thrombin forms complexes in plasma which comigrate with the thrombin-HCII complex during sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS- PAGE); (b) activity detected by the assay is decreased in plasma absorbed with monospecific antibodies against HCII; and (c) purified antithrombin III (ATIII) is unreactive in the assay system. Addition of Polybrene to the assay permits determination of HCII activity in samples containing less than or equal to 12 U/mL of heparin. The range of HCII concentrations in normal individuals is 1.2 +/- 0.4 mumol/L (mean +/- 2 SD, n = 34). HCII activity was determined in 54 consecutive patients undergoing evaluation for the possibility of disseminated intravascular coagulation (DIC). Ten of the 11 patients with documented DIC had decreased HCII activity as compared with only 7 of the 43 patients without DIC (chi 2 = 19.3, P less than .0001). The concentrations of HCII and ATIII varied in parallel in most of the patients tested. A significant correlation between decreased HCII activity and decreased serum albumin concentration was also observed in these patients and in eight additional patients with hepatic failure in the absence of DIC. We conclude that HCII activity is decreased in many patients with DIC and hepatic failure.     

Prevention of deep vein thrombosis in cancer patients

Venous thromboembolism (VTE) in patients with cancer follows an aggressive course, and it is often resistant to traditional regimens of pharmacological prophylaxis and treatment. Anticoagulant-related bleeding is also common and can complicate VTE treatment as well as cancer therapy. Consequently, the most effective approach to reducing the burden of VTE and its associated morbidity and mortality is to provide appropriate prophylaxis. Few clinical trials have focused on the prevention of VTE in this high-risk patient population, and they consistently demonstrate the efficacy and safety of anticoagulant prophylaxis in reducing thrombotic complications. Currently, low-molecular-weight heparins and oral vitamin K antagonists are the most commonly used anticoagulants for primary prevention in patients with cancer, but compliance with consensus guidelines is poor. Novel anticoagulants with a convenient and favorable risk/benefit profile may help to improve prophylaxis utilization and treatment. This review will provide a summary of the evidence on the primary prevention of VTE in patients with cancer.