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The effect of subcutaneously administered low-molecular-weight heparin on microarterial thrombosis in the rat.

OBJECTIVE: To examine the effect of administration of a low-molecular-weight heparin derivative, enoxaparin, on the rate of arterial thrombosis in a rat model. STUDY DESIGN: Prospective, randomized, blinded study. METHODS: A standard microarterial anastomosis tuck injury was created in both femoral arteries of 25 Long Evans retired breeder rats. Thirteen animals received a subcutaneous injection of 50 IU/kg of enoxaparin 2 hours before the procedure, while 12 control animals received vehicle (isotonic sodium chloride solution) alone. Sites of injury/repair were assessed 2 hours after the procedure for anastomotic patency or thrombosis. RESULTS: Six (23%) of 26 vessels in the drug-treated group developed an arterial thrombosis at the site of repair, while 6 (25%) of 24 vessels in the control group developed thrombosis. There was no statistically significant difference at the 95% confidence limit between the 2 groups based on a comparison-of-proportions test. CONCLUSION: The preoperative subcutaneous administration of 50 IU/kg of enoxaparin did not alter the rate of arterial thrombosis following the creation of a thrombogenic tuck injury/repair of the rat femoral artery.

Animals↗

Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.

Adolescent↗

Simplification of the diagnostic management of suspected deep vein thrombosis.

BACKGROUND: The standard diagnostic approach in patients with suspected deep vein thrombosis is to repeat the compression ultrasonography after 1 week in all patients with an initial normal result. We hypothesized that a normal finding of a D-dimer assay safely obviates the need for repeated ultrasonography. In addition, we evaluated the potential value of a pretest probability assessment for this purpose. METHODS: At presentation, consecutive outpatients with suspected thrombosis underwent independent assessment by means of ultrasonography of the proximal veins, a whole-blood D-dimer assay, and a pretest clinical model. Patients with normal ultrasonographic findings and an abnormal D-dimer assay result were scheduled for repeated ultrasonography. We evaluated the incidence of symptomatic venous thromboembolic complications during a 3-month follow-up, and the value of clinical pretest probability with ultrasonography or D-dimer assay in scenario analyses. RESULTS: We studied 1756 patients with prevalence of thrombosis of 22%. At entry, results of the D-dimer assay and ultrasonography were normal in 828 patients (47%). Of these, 6 returned with confirmed symptomatic venous thromboembolism (complication rate, 0.7%; 95% confidence interval [CI], 0.3%-1.6%). Repeated ultrasonography was avoided in 61% of the patients with an initial normal test result. Scenario analyses disclosed that the complication rate was 1.6% (95% CI, 0.8%-2.6%) in those with a low clinical pretest probability and a normal result of ultrasonography at referral, whereas this figure was 1.8% (95% CI, 0.9%-3.3%) in patients with a low clinical probability result and a normal result of the D-dimer assay at referral. CONCLUSIONS: It is safe to withhold repeated ultrasonography in patients with suspected deep vein thrombosis who have normal results of ultrasonograpy and the SimpliRED D-dimer assay at presentation. The combination of a low clinical pretest probability with a normal result of compression ultrasonography or the D-dimer assay appears to be equally safe in refuting the diagnosis of deep vein thrombosis.

Adolescent↗

A pilot randomized double-blind comparison of a low-molecular-weight heparin, a nonsteroidal anti-inflammatory agent, and placebo in the treatment of superficial vein thrombosis.

BACKGROUND: The efficacy and safety of antithrombotic treatment in patients with superficial vein thrombosis remain to be established in adequately designed trials. METHODS: In a double-blind trial, 427 patients older than 18 years, with documented acute symptomatic superficial vein thrombosis of the legs, were randomly assigned to receive subcutaneous enoxaparin sodium, 40 mg; subcutaneous enoxaparin, 1.5 mg/kg; oral tenoxicam; or placebo, once daily for 8 to 12 days. The primary efficacy outcome was deep venous thromboembolism between days 1 and 12, defined as deep vein thrombosis detected by ultrasonography between days 8 and 12 or earlier if clinically indicated, or documented symptomatic pulmonary embolism. For the secondary efficacy outcomes, superficial vein thrombosis recurrence or extension was also considered. RESULTS: The incidence of deep venous thromboembolism by day 12 was 3.6% (4 of 111 patients) in the placebo group, 0.9% (1 of 109 patients) in the 40-mg enoxaparin group (P =.37 vs placebo), 1.0% (1 of 102 patients) in the 1.5-mg/kg enoxaparin group (P =.37 vs placebo), and 2.1% (2 of 94 patients) in the tenoxicam group (P =.69 vs placebo). The incidence of deep and superficial venous thromboembolism by day 12 was significantly reduced in all active treatment groups, from 30.6% (34 of 111 patients) in the placebo group to 8.3% (9 of 109 patients), 6.9% (7 of 102 patients), and 14.9% (14 of 94 patients) in the 40-mg enoxaparin (P<.001), 1.5-mg/kg enoxaparin (P<.001), and tenoxicam (P<.01) groups, respectively. No death or major hemorrhage occurred during the study. CONCLUSION: Treatment with a low-molecular-weight heparin or with an oral nonsteroidal anti-inflammatory agent should be evaluated further in the prevention of thromboembolic complications in patients with superficial vein thrombosis.

Adult↗

Deep vein thrombosis in elderly patients hospitalized in subacute care facilities: a multicenter cross-sectional study of risk factors, prophylaxis, and prevalence.

BACKGROUND: The efficacy of venous thromboembolism prophylaxis has not been established, to our knowledge, in elderly patients hospitalized in subacute care facilities. OBJECTIVES: To describe risk factors and physician practices in the prevention of venous thromboembolism and to estimate the prevalence of deep vein thrombosis. METHODS: A multicenter cross-sectional study was conducted in the subacute care departments of 36 French hospitals. The study population included 852 inpatients older than 64 years. Systematic ultrasound examination was performed by angiologists. RESULTS: Of the 852 inpatients, 178 (20.9%; 95% confidence interval [CI], 18.2%-23.8%) had 3 or more risk factors other than age, while 144 patients (16.9%; 95% CI, 14.4%-19.6%) had none. The rate of prophylactic anticoagulant treatment was 56.1%, ranging from 20.0% to 86.9%, depending on the department. In multivariate analysis, prophylaxis use was associated with acute immobilization (odds ratio [OR], 4.17; 95% CI, 2.48-7.01), chronic immobilization (OR, 3.19; 95% CI, 2.22-4.60), major surgical procedure (OR, 6.81; 95% CI, 4.26-10.88), and congestive heart failure (OR, 1.65; 95% CI, 1.02-2.67). Prophylaxis use was low in patients who had cancer (OR, 0.49; 95% CI, 0.29-0.84) or myocardial infarction (OR, 0.39; 95% CI, 0.14-1.00). It was not significantly associated with paralytic stroke or history of venous thromboembolism. Deep vein thrombosis was detected in 135 patients (15.8%; 95% CI, 13.4%-18.5%): 50 (5.9%; 95% CI, 4.4%-7.7%) had proximal vein thrombosis and 85 (10.0%; 95% CI, 8.0%-12.2%) had calf vein thrombosis. CONCLUSIONS: The prevalence of deep venous thrombosis is high in these patients, despite wide use of prophylaxis. Further prospective studies assessing the clinical benefit of extended duration prophylaxis are needed in elderly patients hospitalized in subacute care settings.

Aged↗

Clopidogrel use for reducing the rate of thrombosis in a rat model of microarterial anastomosis.

OBJECTIVES: The national success rate for microvascular free tissue transfer is around 94%. However, in cases of failure, which is most often due to thrombosis in the vascular pedicle, the morbidity can be significant. Microvascular surgeons have used various pharmacologic agents to reduce thrombosis rates; however, none have been ideal. We examined the effects of clopidogrel bisulfate (Plavix), a member of the relatively new class of antiplatelet agents, on the rate of arterial thrombosis in a rat model. DESIGN: Prospective randomized, blinded. SETTING: Tertiary care academic medical center. SUBJECTS: Male Sprague-Dawley rats weighing between 350 and 400 g. INTERVENTION: Clopidogrel or placebo via gavage. After waiting 2 hours for absorption and activation, the "tuck" model of microvascular anastomosis was performed on both femoral arteries. Arteries were transected after 3 hours and patency was assessed. MAIN OUTCOME MEASURES: Bleeding time was obtained by determining the time to clot after removal of 2 mm from the tail tip. Vessel patency was assessed after 3 hours in the clopidogrel-treated and control groups. RESULTS: Of 33 arteries, 19 (58%) in the control group developed complete thrombosis by the end of the period compared with only 6 (19%) of 32 arteries in the group that received clopidogrel. Chi(2) analysis revealed this to be significant (P = .001). The mean (SD) bleeding time in the control group was 158 (44) seconds compared with 233 (48) seconds in the clopidogrel group. CONCLUSIONS: Clopidogrel significantly reduced the rate of arterial thrombosis in a rat model of microvascular repair. The average bleeding time in the clopidogrel group was prolonged, suggesting that absorption and activation occurred. These preliminary data suggest a potential role for clopidogrel in select high-risk patients undergoing microvascular free tissue transfer.

Anastomosis, Surgical↗

A prospective study of a focused, surgeon-performed ultrasound examination for the detection of occult common femoral vein thrombosis in critically ill patients.

HYPOTHESIS: A focused, surgeon-performed ultrasound examination of the common femoral veins is an accurate screening tool for the detection of common femoral vein thrombosis in high-risk, critically ill patients. DESIGN: A prospective study using a focused ultrasound examination for findings consistent with deep vein thrombosis of the common femoral veins. The results of these examinations were compared with those of duplex imaging or computed tomographic venography studies. SETTING: Surgical intensive care unit. PATIENTS: All critically ill patients who were admitted to the surgical intensive care unit and considered to be at high risk for the development of deep vein thrombosis. MAIN OUTCOME MEASURE: Presence of deep vein thrombosis in the common femoral veins. RESULTS: During a 16-month period, surgeons performed 306 ultrasound examinations on 220 critically ill surgical patients. The results included 295 true negative, 9 true positive, 1 false negative, and 1 false positive, yielding a 90.0% sensitivity, 99.6% specificity, and 99.3% accuracy. CONCLUSION: A focused, surgeon-performed ultrasound examination is a rapid and accurate screening method to detect common femoral vein thrombosis in critically ill patients as well as to examine those patients in whom pulmonary embolism is strongly suspected.

Adult↗

Aortic thrombosis after umbilical artery catheterization.

Neonatal arterial thrombosis has become more common with the use of umbilical artery catheters; however, catheter-induced aortic thrombosis is rare. A review of the literature disclosed a 100% mortality from medically managed neonatal aortic thrombosis. Two cases of umbilical artery catheterinduced acute neonatal thrombosis were managed successfully by surgical thrombectomy. Severe lower extremity ischemia and hypertension with aortic occlusion developed in two neonates, and intractable congestive heart failure developed in one of the neonates. This seems to be the first documented report of successful surgical treatment of umbilical artery catheter-induced aortic thrombosis. Acute neonatal aortic occlusion should be considered a surgical emergency.

Acute Disease↗

Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation.

We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery. The arterial flow was reestablished and maintained in 5 (38.5%) of the 13. Recurrent thrombosis in the other 8 grafts developed 2 to 24 days (mean, 13.8 days) after transplantation. Reconstruction was successful in 50% (4/8) of the adults, compared with only 20% (1/5) of the children. Satisfactory results were obtained when a definitive cause of thrombosis could be identified. We conclude that early recognition and correction of the cause of hepatic artery thrombosis during or after orthotopic liver transplantation, especially in adults, is often a graft-saving and lifesaving procedure worthy of consideration.

Adolescent↗

Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution.

Heparin-induced thrombocytopenia with thrombosis (HITT) can lead to serious morbidity and may be potentially fatal. We reviewed our experience with this entity over a 4-year period, to determine the following: 1) incidence and type of thrombosis in patients with heparin-induced thrombocytopenia (HIT), 2) clinical consequences of thrombosis, i.e., amputation, cerebrovascular accidents and death, 3) risk factors associated with development of thrombosis, and 4) impact of therapy on clinical outcomes in patients with HITT. Between 1991-1994, 108 patients were diagnosed to have HIT by heparin-induced platelet aggregation test. Thirty-two (29%) of these developed thrombotic complications, of which 20 were venous, 8 arterial, and 4 both. Five of the 32 died, 3 underwent amputations, and 3 had cerebrovascular accidents. The patients who developed thrombotic complications, when compared to those with HIT alone, were older (68.7 +/- 11.5 vs. 63.3 +/- 16 years, P = .05), had more severe thrombocytopenia (platelet count 46,300 +/- 30,400/mm3 vs. 62,500 +/- 34,400/mm3, P = .02), and developed it earlier (6.0 +/- 2.9 vs. 7.4 +/- 3.1 days, P = .03). Multivariate analysis showed that severity of thrombocytopenia and early fall in platelet count were independent risk factors for development of thrombotic complications. We did not find an association between development of thrombosis and clinical events (myocardial infarction, cardiac procedures or surgery, noncardiac surgery, and sepsis) that occurred immediately prior to onset of thrombocytopenia. Heparin was stopped in all 32 patients with HITT. Six received no additional therapy, and one received a single dose of aspirin. Three of these 7 died. The other 25 received anticoagulant or multiagent therapy, with 2 deaths. The death rate was lower in those who were treated with anticoagulant or multiagent therapy (P = .05). We conclude that: 1) Thrombotic complications occur in about 29% of hospitalized patients who develop HIT. 2) Early, severe fall in platelet count in elderly patients receiving heparin appears to be associated with development of thrombotic complications. 3) Our data do not show an association between development of thrombotic complications and clinical events immediately preceding the diagnosis of HIT. 4) In addition to discontinuation of heparin, anticoagulant or thrombolytic therapy should be considered in patients with HITT.

Anticoagulants↗

Activated protein C resistance and the factor V Leiden mutation in children with thrombosis.

To determine the prevalence of activated protein C resistance and the factor V Leiden mutation (position 1691, arginine 506 to glutamine substitution) in children with thrombosis, plasma samples from children with thrombosis were tested for activated protein C resistance. DNA was analyzed for the factor V Leiden mutation. Five of 34 children (15%) had activated protein C resistance; each was heterozygous for the factor V Leiden mutation. All 5 children heterozygous for the factor V Leiden mutation suffered non-CNS venous thromboses comprising 21% of the group of children (5/24) with non-CNS venous thrombotic events. Each of these 5 children had a family history of thrombosis. In conclusion, children with non-CNS venous thrombosis should be evaluated for the factor V Leiden mutation. Children most likely affected are those with a family history of thrombosis.

Adolescent↗

Causes of venous thrombosis in fifty Chinese patients.

In a whole year from July 1997 to June 1998, a total of 50 patients with sonogram-proved venous thrombosis who called on our hematology clinic consecutively entered into the study. Their mean age was 59.1 +/- 17.5 years, range 18-83 years, and 29 were male. A series of examinations were performed in order to find out the cause of venous thrombosis. These examinations included antithrombin, protein C, protein S, plasminogen, heparin cofactor II, activated protein C ratio, factor V Leiden mutation, fibrinogen, factors VIII and XII, euglobulin lysis time, 677 C-->T mutation of methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210 (PT 20210) A allele mutation, lupus anticoagulant, anticardiolipin antibody, and complete blood count. Five patients (10%) were found to have malignancy; an inferior vena cava thrombosis in one patient was due to venous compression by hydronephrosis; two patients had lupus anticoagulant; two had varicose veins of legs; two had protein C deficiency; four had protein S deficiency; two had plasminogen deficiency; two had antithrombin deficiency. No activated protein C resistance, elevated factor VIII level, factor V Leiden, PT 20210 A allele or heparin cofactor II deficiency was found in the present study. Homozygous MTHFR 677 C-->T gene mutation was found in 7 patients (14%); one of them also had a plasminogen deficiency. No possible risk factor of venous thrombosis could be found in 24 patients (48%). In conclusion, malignancy and protein S deficiency were the most frequent acquired and congenital causes of venous thrombosis in the Chinese, respectively.

Adenocarcinoma↗

Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters.

BACKGROUND: Peripherally placed percutaneous central venous catheters (PCVC) are used in neonates to provide long-term vascular access. Major complications associated with these catheters include mechanical complications (catheter thrombosis, occlusion or dislodgement) and infection. Strategies to prevent catheter thrombosis and occlusion include the use of heparin. Systematic review has revealed that heparin is effective in prolonging the umbilical arterial catheter stay in neonates. However, heparin is known to be associated with complications such as bleeding and thrombocytopenia which may result in serious long-term sequelae. OBJECTIVES: The primary objective is to assess the effectiveness of heparin for prevention of catheter related thrombosis. The secondary objectives are to assess the effectiveness of heparin on catheter occlusion, duration of catheter patency, catheter related sepsis and complications associated with the use of heparin. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) and abstracts from the annual meetings of the Society for Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2005). No language restrictions were applied. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: the population had to be neonates, intervention had to be heparin infusion compared to placebo or no treatment for prevention of any of the complications related to peripherally placed PCVC, the trial had to be randomized or quasi-randomized and at least one of the primary or secondary outcomes reported. DATA COLLECTION AND ANALYSIS: The methodological quality of included trials was assessed using criteria for masking of randomization, masking of intervention, completeness of follow-up and masking of outcome measurement. Data on relevant outcomes were extracted and the effect size was estimated by calculating relative risk (95% CI), risk difference (95% CI) and weighted mean difference (95% CI). MAIN RESULTS: Two randomized trials on the use of heparin for peripherally placed PCVC were identified . One trial (Kamala et al) of 66 neonates of adequate methodology met the eligibility criteria. There was no statistically significant differences in the incidence of thrombosis (RR 0.79, 95% CI 0.35, 1.79), occlusion (RR 0.63, 95% CI 0.22), catheter related sepsis (RR 0.89, 95% CI 0.06, 13.57), extension of intraventricular hemorrhage (RR 0.87, 95% CI 0.25, 3.03), mortality (RR 0.59, 95% CI 0.18, 1.90) or duration of catheter patency (WMD 1.50 days, 95% CI -1.35 days, 4.35 days) between heparin and no heparin groups. Another trial (Betremieux et al) was excluded due to several methodological issues: 1. randomization was at the time of umbilical catheter placement rather than later PCVC placement 2. multiple PCVC were used in some infants, with reported results based on number of catheters rather than infants. AUTHORS' CONCLUSIONS IMPLICATIONS FOR PRACTICE: Prophylactic use of heparin for prevention of complications related to peripherally placed PCVC has been examined in only one randomized controlled clinical trial that was eligible for inclusion in this review. No significant differences in the incidence of thrombosis, occlusion, sepsis, mortality and duration of catheter patency were observed. With the current state of knowledge, routine use of heparin for this purpose can not be recommended. Implication for research: Increasing survival of extremely low birth weight infants may be accompanied by prolonged intravenous access for nutrition. Well designed randomized controlled trials of sufficient power to determine the benefits and risks of continuous infusion of heparin in neonates with peripherally inserted PCVC are warranted.

Anticoagulants↗

Mesenteric venous thrombosis occurring late after splenectomy.

Two patients with mesenteric venous thrombosis which occurred late after splenectomy are reported. In the first case the thrombosis was seen, with preceding thrombocytosis, 3 years after splenectomy. In the second case the thrombosis occurred 2 years and 5 months postoperatively. Platelet counts had not been obtained before the mesenteric thrombosis in this case. In both instances persistent severe anaemia for several weeks preceded the symptoms and signs of mesenteric venous thrombosis. Both patients were treated by extended resection of the affected small bowel. Thus, dangerous thrombocytosis may occur in the presence of persistent severe anaemia even late after splenectomy. Thrombocytosis occurring immediately after splenectomy, which is almost inevitable, should be treated with heparin or other anticoagulants. In the late period the avoidance of persistent severe anaemia seems to be important in the prevention of thrombotic complications due to reactive thrombocytosis in splenectomized patients.

Adult↗

Treatment of coronary stent thrombosis with rheolytic thrombectomy: results from a multicenter experience.

The objective of this study was to assess the feasibility, efficacy, and safety of rheolytic thrombectomy (RT) for treatment of coronary stent thrombosis. Stent thrombosis is an infrequent but potentially devastating complication. Conventional treatment with balloon angioplasty and/or thrombolysis has yielded suboptimal results. RT was used to treat 18 patients (mean age, 62 +/- 8 years; 72% male) with in-stent thrombosis (mean time to stent thrombosis, 2.4 +/- 1.8 days). Device success, procedure success, in-hospital and 30-day major cardiovascular events (MACE) were assessed in the hospital and at 30 days. Device success was obtained in 94% and procedure success was achieved in 100% of patients. Following RT, 11 patients underwent balloon angioplasty and 7 patients received additional stents. TIMI 3 coronary flow was obtained in 94.4% and all (100%) patients achieved either TIMI 2 or 3 coronary flow. The angiographic thrombus area decreased from 113.7 +/- 79 to 5.5 +/- 5.7 mm(2) after RT, and to 0.9 +/- 2.1 mm(2) (P < 0.001) after final treatment. Procedural complications were limited to transient no-reflow in five patients. Only one patient evolved a Q-wave MI. At 30 days of follow-up, no patients suffered death, emergent bypass surgery, or stroke. Our data suggest that the adjunctive use of rheolytic thrombectomy offers improved outcomes compared to prior results of intervention after coronary stent thrombosis and should be strongly considered as a treatment option for this complication.

Aged↗

Hypothesis: warfarin administered simultaneously with heparin infusion will prevent heparin-discontinuance associated coronary thrombosis.

Recent studies have evidenced an association between the time of heparin discontinuance and coronary artery reocclusion. Some investigators have concluded that inadequate heparinization was responsible, and further heparin infusion or an increase in dose would have been indicated. However, several investigators (Rao: Thrombosis Research 24:181-186, 1981; Marciniak and Gockerman: Lancet September 17:581-584, 1977; Fisken et al.: Lancet December 10: 1231, 1977; Conard et al.: Thrombosis Research 22:507-511, 1981; Kakkar et al.: Lancet January 12:103-104; Green: Lancet February 16:374, 375; Harborne and Nicolaides: Thrombosis Research 43:657-662, 1986; Bonen et al.: Thrombosis Research 27:123-124, 1982; Blomback et al.: Acta Physiologica Scandinavica 58:306-318, 1963; Holm et al.: Scandinavian Journal of Haematology 35:564-569, 1985; Andersson et al.: Thrombosis Research 34:333-340, 1984) have demonstrated that antithrombin III levels are reduced in patients on intravenous heparin. Both reduced antithrombin III levels and reduced rate of antithrombin inhibition of thrombin at the time of heparin discontinuance may increase the risk of coronary rethrombosis. If this theory is correct, increasing heparin infusion may exacerbate this risk. We propose an investigation that will provide evidence for or against the decreased antithrombin III theory, and in doing so, test an experimental therapy designed to prevent coronary reocclusion upon heparin discontinuance. In a randomized, placebo-controlled double-blinded study, we will determine whether simultaneous administration of warfarin with heparin initiation provides more time to increase antithrombin III levels and prevent coronary reocclusion upon heparin discontinuance, compared to heparin without warfarin therapy.

Antithrombin III↗

Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia.

BACKGROUND: There is currently insufficient evidence to either support or refute an association between estrogen-based hormone treatment (EBHT) and thrombosis risk in essential thrombocythemia (ET). METHODS: A retrospective review of thrombotic events, which occurred both at diagnosis of ET and during subsequent follow-up, was performed in a consecutive cohort of women with WHO-defined ET seen at the Mayo Clinic. Details of EBHT were concomitantly obtained. RESULTS: A total of 305 women were seen during the study period and followed for a median of 133 months. EBHT at diagnosis was documented in 59 women and such therapy was instituted at a variable time after diagnosis in 34 additional patients. At diagnosis, major thrombosis occurred in 73 patients (24%), including 11 of 59 (19%) on EBHT and 62 of 246 (25%) not on EBHT (P=.28). Thrombosis after diagnosis occurred in 94 patients (31%), including 64 of 212 (30%) not on EBHT, 5 of 17 (29%) in whom EBHT was discontinued at diagnosis, 13 of 42 (31%) in whom EBHT was continued despite the diagnosis of ET, and 12 of 34 (35%) in whom EBHT was started after diagnosis (P=.95). The overall results were the same when arterial and venous events were analyzed separately. However, EBHT in the form of oral contraceptives (OCP) was associated with an increased risk of venous thrombosis (P=.03). CONCLUSIONS: EBHT is safe in ET outside the setting of OCP use, which might be associated with an increased risk of deep vein thrombosis.

Adolescent↗

Deficiency of protein C in patients with portal vein thrombosis.

Portal vein thrombosis has been considered idiopathic in 50% of cases reported in adults. Protein C deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein C was present. Both cases were very similar, with a history of recurrent episodes of systemic thromboembolic disease, mesenteric venous thrombosis that required intestinal resection and upper gastrointestinal bleeding from gastroesophageal varices. Portal hypertension as well as portal vein thrombosis were demonstrated. The hematologic work-up revealed a deficiency of protein C. Both patients were subjected to the Sugiura procedure, and anticoagulation was instituted thereafter. At the time of surgery, a liver biopsy was performed, which was reported as "normal." Two years and 3 months, respectively, after surgery both patients are in good condition. We conclude that protein C deficiency should be investigated in all cases of portal vein thrombosis, especially in those with a history of thromboembolic disease elsewhere.

Adult↗