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Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.

BACKGROUND: Patients who have had an episode of symptomatic venous thromboembolism are usually treated for at least five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin. Thereafter, they received a three month course of a vitamin K antagonist, with a dose adjusted to achieve an International Normalized Ratio between 2.0 and 3.0. Some patients have contraindications to vitamin K antagonists. In addition, treatment with vitamin K antagonists has the disadvantage of regular laboratory measurements. OBJECTIVES: The objective of this review was to evaluate the efficacy and safety of long-term treatment of symptomatic venous thromboembolism with low-molecular-weight heparins compared with vitamin K antagonists. SEARCH STRATEGY: Computerized searches of MEDLINE, EMBASE and Current Contents were made and relevant journals were hand-searched using the search strategy described by the Cochrane Peripheral Vascular Disease Group. In addition, randomized clinical trials were located through personal communication with colleagues. Where necessary, the reviewers contacted pharmaceutical companies for further information. SELECTION CRITERIA: Two reviewers evaluated studies independently for methodological quality. DATA COLLECTION AND ANALYSIS: Two reviewers reviewed and extracted data independently using a standard form. Primary analysis concerned all patients in the studies during the period of randomized treatment. Additional separate analyses were performed for category I and category II studies; studies that used similar initial treatments in both study arms and those that used different treatment regimes during the initial treatment; and the total period of follow-up in the different studies. MAIN RESULTS: Five studies were identified that fulfilled our predefined criteria (three category I and two category II studies). When all five studies were combined, a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.72; 95% CI [0.42, 1.23]) was found. In category I studies, analysis of the pooled data showed a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). This OR was mainly due to one possibly confounded study, and after omitting this study from the analysis a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). No differences in the risk of bleeding (OR 0.63; 95% CI [0.21, 1.88]) and mortality (OR 1.13; 95% CI [0.47, 2.69] were observed. REVIEWER'S CONCLUSIONS: Low-molecular-weight heparins are possibly as effective and safe as vitamin K antagonists in the prevention of recurrent symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but have the disadvantage of much higher medicinal costs. Treatment with low-molecular-weight heparin is possibly a safe alternative in some patients; for example patients who live in geographically inaccessible places; patients who are reluctant to go to the thrombosis service on a regular basis; and patients with contraindications to vitamin K antagonists (e.g. pregnant women). Therefore, in the absence of definitive evidence on the safety and efficacy of low-molecular-weight heparins compared with vitamin K antagonists, we believe that treatment with vitamin K antagonists is still the treatment of choice in the prevention of recurrent symptomatic venous thromboembolism after an episode of deep venous thrombosis, in the majority of patients.

Anticoagulants↗

Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE).

PURPOSE: We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism. SUBJECTS AND METHODS: In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years). RESULTS: A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count. CONCLUSIONS: In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.

Aged↗

Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Duration of Anticoagulation Study Group.

PURPOSE: To compare the risk of recurrent venous thromboembolism in patients with and without antiphospholipid antibodies. PATIENTS AND METHODS: Anticardiolipin antibodies were tested 6 months after a first or second episode of venous thromboembolism. Of the patients with a first episode of venous thromboembolism only the 412 who received 6 months of anticoagulation were studied. Two hundred and eleven patients with a second episode received oral anticoagulation for 6 months or indefinitely. The therapy was targeted at an international normalized ratio (INR) of 2.0 to 2.85. All patients were followed up for 4 years after enrollment. RESULTS: Among the 412 patients with a first episode of venous thromboembolism the risk of recurrence was 29% in patients with anticardiolipin antibodies and 14% in those without antibodies (P = 0.0013). In those with antibodies, there was an increased risk during the first 6 months after cessation of anticoagulation. The risk of recurrence increased with the titer of the antibodies. Four-year mortality rate was 15% in those with antibodies and 6% in those without (P = 0.01). Among 34 patients with a second event of venous thromboembolism and anticardiolipin antibodies, there were no recurrences during anticoagulant therapy versus 20% in those who received only 6 months of treatment (P = 0.08). CONCLUSIONS: The presence of elevated titers of anticardiolipin antibodies 6 months after an episode of venous thromboembolism is a predictor for an increased risk of recurrence and of death. Patients with anticardiolipin antibodies and venous thromboembolism seem to benefit from prolonged oral anticoagulation.

Aged↗

Heparin resistance as detected with an antifactor Xa assay is not more common in venous thromboembolism than in other thromboembolic conditions.

STUDY OBJECTIVE: To identify whether heparin resistance when measured with an antifactor Xa assay is more frequent in patients with venous thromboembolic disease than in patients with other thromboembolic conditions. DESIGN: Prospective observational cohort study. SETTING: A 625-bed, adults-only, private teaching hospital. PATIENTS: Three hundred seventy-two patients receiving intravenous unfractionated heparin for a variety of indications classified as either venous thromboembolism or arterial thromboembolism. INTERVENTION: All patients received an initial unfractionated heparin dosage according to a protocol based on age and estimated blood volume. Targeted antifactor Xa was 0.35-0.65 U/ml. MEASUREMENTS AND MAIN RESULTS: A modest increase in heparin dosage requirement was noted in patients with venous thromboembolism that was entirely related to lower hemoglobin concentration in that group compared with the arterial thromboembolism group. Low hemoglobin concentration was significantly associated with increased heparin resistance regardless of treatment indication. CONCLUSIONS: True heparin resistance seen with an antifactor Xa assay is not more common in venous thromboembolism than in other conditions. Low hemoglobin concentration, rather than treatment indication, appears to be associated with increased heparin resistance.

Adolescent↗

Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke.

OBJECTIVE: Deep venous thromboembolism (DVT) is an important health issue in the hospitalized geriatric population that leads to increased length of stay, morbidity, and mortality. Patients with hemorrhagic strokes are usually not placed on prophylactic therapy because of the risk of hemorrhagic extension of the stroke. The purpose of this study was to evaluate the prevalence of DVTs in hospitalized patients with hemorrhagic vs. thromboembolic strokes. DESIGN: Retrospective chart review of data obtained from the Maryland Health Services Cost Review Commission data base for 1999 to determine the prevalence of DVTs in both hemorrhagic and thromboembolic stroke patients hospitalized acutely. Multiple logistic regression was performed to evaluate possible risk factors. RESULTS: There were 1926 patients hospitalized with a primary diagnosis of hemorrhagic stroke and 15599 with thromboembolic stroke. Women in general had more strokes than men did. Older patients were more likely to have strokes as evidenced by the mean ages of 66 and 71 yr for hemorrhagic and thromboembolic strokes, respectively. A total of 37 patients (1.9%) with hemorrhagic strokes had DVTs, whereas 74 patients (0.5%) with thromboembolic strokes had DVTs. Hemorrhagic stroke was an independent risk factor for DVT (odds ratio, 2.60; 95% confidence interval, 1.49-4.55; P = 0.0008). CONCLUSIONS: DVT prevalence and risk was higher among patients with hemorrhagic strokes in comparison with patients with thromboembolic strokes.

Age Factors↗

Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism.

To establish the prevalence of antibodies against beta2-glycoprotein I (beta2GPI) in unselected patients with venous thromboembolism, as well as the association with antiphospholipid antibodies (aPL) and a history of previous thromboembolism, we investigated the presence of these antibodies in 227 consecutive patients with acute deep vein thrombosis or pulmonary embolism, of whom 63 were carriers of aPL with or without lupus anticoagulant (LA), and seven were carriers of LA alone. The presence of antibodies against beta2GPI was demonstrated in 19 patients [8.4%; 95% confidence interval (CI), 4.5-11.3%]. All of them belonged to the group of 63 patients with aPL (30.2%). A history of a previous thromboembolism was identified in 11 of the 19 patients with anti-beta2GPI antibodies (57.9%) and in 45 of the 208 patients without these antibodies [21.6%; odds ratio (OR)=4.98; 95% CI, 1.89-13.1; p<0.0005]. In the subgroup of patients with aPL and/or LA, the rate of recurrent thromboembolism among patients with anti-beta2GPI antibodies (11 of 19, 57.9%) was significantly higher than that observed in patients without these antibodies (15 of 51, 29.4%; OR=3.3; 95% CI, 1.1-9.83; p=0.28). We conclude that in patients with acute venous thromboembolism the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies seems to identify a subgroup of patients with antiphospholipid antibodies who have a peculiarly high risk of thrombotic recurrences. Further prospective studies are indicated to better define the role of anti-beta2GPI antibodies in the development of recurrent thromboembolism.

Acute Disease↗

[Factor XII (Hageman factor) deficiency: a risk factor for development of thromboembolism. Incidence of factor XII deficiency in patients after recurrent venous or arterial thromboembolism and myocardial infarction].

103 patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (F XII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with F XII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined F XII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in F XII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of F XII deficiency was significantly higher (20%, p < 0.003). In 67% of the patients with F XII deficiency a positive family history of thrombosis could be established. In contrast, only 32% (p = 0.043) of all venous and 28% (p = 0.019) of all arterial thrombosis patients had a positive family history. We believe that reduced levels of F XII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of F XII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Adult↗

Haemorrhagic and thromboembolic complications versus intensity of treatment of venous thromboembolism with oral anticoagulants.

In order to assess the recommended therapeutic interval with the prothrombin complex analysis, using Stago Prothrombin-complex Assay (SPA) as the reagent, a retrospective multicentre study was performed to obtain clinical documentation. All thromboembolic and haemorrhagic complications during secondary prophylaxis after venous thromboembolism in 272 patients were recorded and related to the intensity of the oral anticoagulation. Six thromboembolic complications in patients without a malignant disease occurred at SPA levels greater than or equal to 28%, confirming that the limit of the therapeutic range, determined by the risk of thromboembolic recurrences, should be set at an SPA level of 25% (international normalized ratio, INR = 2.0), at least in venous disease. Major haemorrhages occurred mainly at SPA levels less than 10% (INR greater than 4.0), unless underlying risk factors were present, thus setting the other limit of the therapeutic range. However, an adjustment of this limit to SPA = 15% (INR approximately 3.0) is suggested, since it would lead to further reduction of haemorrhage and is advisable in most patients with venous thromboembolism.

Adult↗

Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.

PURPOSE: Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR. PATIENTS AND METHODS: In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0. RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0. CONCLUSION: Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.

Aged↗

Multicentre hospital drug utilization study on the prophylaxis of venous thromboembolism. The Venous Thromboembolism Study Group of the Spanish Society of Clinical Pharmacology.

1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Postoperative recurrence of venous thromboembolism in patients with episodes of preoperative thromboembolism].

BACKGROUND: Venous thromboembolism (VTE) has become a major health problem in Japan. METHODS: We examined, postoperative recurrence of VTE in patients with preoperative venous thromboembolic events and evaluated factors that are relevant to the occurrence of postoperative VTE. RESULTS: Forty-four cases out of 38500 had been diagnosed preoperatively as having VTE in the period of 1995-2001 at Kitasato University Hospital. Postoperative VTE was detected in four patients (9%) out of these 44 cases. Patients who had thrombophilia (antiphosholipid syndrome) or recent episode of VTE within 1 month were higher in the incidence of postoperative recurrence of VTE than the others. Temporary infra-vena cava filters were placed to prevent pulmonary thromboembolism in twelve patients. In 8 of the patients, thrombi were detected in or at the filter before explantation. Three patients (7%) had undergone thrombolysis therapy. Postoperative VTE was not found in patients who had already received anticoagulant therapy (warfarin) for 3 or more months. CONCLUSIONS: It is concluded that newly developed VTE occurred perioperatively in 9% of patients with preoperative VTE, and that thrombophilia and a recent episode of VTE were considered as risk factors of perioperative VTE. Temporary infra-vena cava filters are a valuable device for prevention of postoperative pulmonary thromboembolism.

Adult↗

A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery.

Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli.

Adult↗

Thromboembolism in patients with prosthetic heart valves. An adequately controlled intense anticoagulant therapy and its influence on the occurrence of thromboembolism in relation to valve type.

This study was designed to evaluate the efficacy of carefully controlled treatment with oral anticoagulants in patients with different mechanical heart valve prostheses. One hundred eighty-one patients with various types of prosthetic valves (mitral 89, aortic 87, combined 5) received oral anticoagulation aiming at Thrombotest (TT) values between 5% and 12%. Median follow-up was 46 months; 80.8% of all TT determinations were below 12%. The thromboembolic rate was 0.25%/year in patients with aortic valve replacement (AVR) and 4.87%/year in patients with mitral valve replacement (MVR). There was a strikingly lower incidence of thromboembolism with newer types of valves (Björk-Shiley convex-concave) in the mitral position under exactly the same intensity and stability of anticoagulant treatment. Clinically overt valve occlusion could be almost completely prevented (0.12%/year) in prostheses at both sites. Severe hemorrhage occurred at a rate of 1.71%/year and fatal bleeding at a rate of 0.37%/year. Our results indicate that carefully controlled anticoagulation is effective in the reduction of thromboembolic complications at a reasonable risk of bleeding.

4-Hydroxycoumarins↗

Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism: results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research.

The incidence of acute pulmonary thromboembolism (APTE) in Japan is quoted as being extremely low compared with the United States, and the incidence and clinical characteristics of chronic pulmonary thromboembolism (CPTE) in Japan is unknown, so this study investigated these aspects of CPTE in 309 patients with APTE and 68 patients with CPTE. The ratio of the incidence of CPTE to APTE was 0.22 and there was no significant difference in age or sex between the APTE and CPTE patients. All of the predisposing factors for pulmonary thromboembolism, except for thrombophilia, were more frequently seen in the patients with APTE. There are some differences in the incidence and clinical characteristics of CPTE compared with APTE between Japanese and American patients in Japan, suggesting that the pathogenesis of CPTE in Japan may differ from that in the USA.

Acute Disease↗

The risk of recurrent venous thromboembolism: the Austrian Study on Recurrent Venous Thromboembolism.

Venous thromboembolism (VTE) is a chronic disease. After withdrawal of oral anticoagulation at least a third of patients will experience a subsequent episode of venous thrombosis. Of these patients, approximately 5% will die from pulmonary embolism. The Austrian Study on Recurrent Venous Thromboembolism (AUREC) is a prospective cohort study aiming to investigate the overall rate of recurrent VTE, the predictive value of laboratory assays, the importance of acquired or congenital risk factors for thrombosis and the impact of extended or modified secondary thromboprophylaxis on the risk of recurrence among high-risk patients. So far, the AUREC investigators have identified subgroups of patients with a particular high risk of recurrence: patients with a history of venous thrombosis, elevated levels of coagulation factors VIII, IX and XI, pulmonary embolism or superficial venous thrombosis and a history of venous thrombosis and hyperhomocysteinemia. Patients with a history of venous thrombosis and mutations in genes encoding for coagulation factors (factor V Leiden, factor II, G20210A) do not have an enhanced risk of recurrence and, thus, do not qualify for extended secondary thromboprophylaxis. At present, interventional trials are in progress in patients with high factor VIII or hyperhomocysteinemia in order to investigate if these patient groups might benefit from extended oral anticoagulation or vitamin supplementation, respectively.

Adolescent↗

Thromboembolism and bleeding after mitral valve replacement with porcine valves: influence of thromboembolic risk factors.

The risk of postoperative thromboembolism (PTE), anticoagulant related hemorrhage (ARH), and the influence of thromboembolic risk factors ( TERF ) were assessed retrospectively in 206 unselected patients undergoing mitral valve replacement (MVR) with porcine xenobioprotheses ( PXBP ). Other aims were to identify the "high-risk" group with respect to PTE and to assess the effectiveness of long-term anticoagulant therapy (AT) in this subset, as well as to elucidate the most adequate method of AT and ascertain if AT is strictly necessary in patients undergoing MVR with PXBP . Patients were divided in two groups: Group I (N = 115) received long-term AT; there were 22 PTE. Group II (N = 91) with only 8 weeks of AT had 2 PTE (P less than 0.01). ARH was the same in both groups. Actuarially , 71.7% of the patients in group I and 96.3% of the patients in group II were free of PTE at 6 years. Long-term AT proved ineffective in preventing PTE and carried a significant incidence of ARH. ARH surpassed PTE (3.5:1) in patients on short-term AT. Patients without TERF have a low incidence of PTE, and AT is not indicated. The "high-risk" group were patients in postoperative atrial fibrillation and left atrial enlargement. One week heparin therapy and 3 months oral AT is suggested for patients with TERF . PXBP for MVR in patients with TERF is significantly thrombogenic. Early operation is advocated to avoid development of TERF that will affect patient outlook after MVR with PXBP due to the significantly increased risks of PTE and (if placed on AT) ARH.

Adult↗

[Prevention of thromboembolism as a cause of thromboembolic complications. A study of the incidence of heparin-induced thrombocytopenia type II].

PROBLEM: A life-threatening complication of the thrombembolism prophylaxis with heparin is heparin-induced thrombocytopenia (HIT) type II. HIT type II is based on immunological mechanisms. Even low, subcutaneously applied doses may produce HIT type II. In those patients, continued application may cause thromboembolic complications. The most important symptom of HIT type II is a decrease of platelets. METHODS: In a prospective study, we investigated the incidence of HIT type II within the period from 01.07.95 to 30.06.96 in orthopedic patients. We also evaluated the importance of the daily platelet count from the fifth postoperative day for the early diagnosis of HIT type II and a possible reduction of the thrombosis rate. The study included 307 patients after primary implantation of hip and knee endoprosthesis and after hip endoprosthesis replacement. All patients received 3 x 5000 IU/d of unfractionated heparin subcutaneously. Whenever there was a decrease of platelets of at least 50% in relation to the preoperative value or whenever thrombembolic complications occurred, serum was analyzed by the heparin-induced platelet activation test (HIPA). RESULTS: 20 patients developed HIT type II. This corresponds to an incidence of 6.5%. 10 of the HIT type II antibody positive patients (50%) developed thrombembolic complications. 3 patients (0.9%) of the group studied developed clinically symptomatic thrombembolic complications without evidence of heparin antibodies. The total risk of getting thrombembolic complications was 4.2% (13 patients). 3.3% (10 patients) of the entire group developed HIT type II antibody associated thrombembolic complications; 1 patient died. The lethality in the HIT type II antibody positive patient group amounted to 5%. The patients with HIT type II received LMW heparinoid Orgaran (AKZO-Organon, The Netherlands) or hirudin (as a clinical trial). The comparison group (retrospective study from 17.10.92 to 16.10.93) was composed of 262 patients with the same operations and equal thromboembolism prophylaxis. The platelet count was made only as part of routine diagnostic tests. 21 patients (8.0%) developed clinically symptomatic thrombembolic complications. The difference in the thrombosis rate between these two groups of patients is statistically significant. Unrecognized HIT type II is probably the reason for the high thrombembolic complication rate in the comparison group. CONCLUSIONS: The daily platelet count from the fifth postoperative day and from the first day in case of reexposure to heparin is an important measure for the early diagnosis of HIT type II.

Adult↗

Relationship between fibrinopeptide A and fibrinogen/fibrin fragment E in thromboembolism, DIC and various non-thromboembolic diseases.

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Collagen Diseases↗