Risk factors of acute pulmonary thromboembolism in Japanese patients hospitalized for medical illness: results of a multicenter registry in the Japanese society of pulmonary embolism research

Background: Although the prophylaxis of acute pulmonary thromboembolism (APTE) in hospitalized patients has been improving in Japan, there is no report concerning APTE of Japanese medical patients. Therefore, the present study was designed to investigate the characteristics of APTE in Japanese patients hospitalized for medical illness, through a retrospective study. Methods: In a total of 1,438 registry patients with pulmonary thromboembolism for recent 10 years, 1,027 patients with APTE were analyzed with respect to underlying diseases or predisposing factors, and clinical course. Results: A hundred thirty three patients hospitalized for medical illness developed APTE, among 433 in-hospital APTE patients. The prevalence of APTE in women was more than in men. The mean age of the patients at diagnosis was 61 ± 17 years. Main risk factors were a prolonged immobilization, stroke, cancer, indwelling central venous catheter. Fifty-four patients had 3 or more risk factors. In-hospital mortality rate was 23%. Conclusions: Japanese patients in this registry had almost the same findings as in western patients, except for some points that had the possibility of demonstrating a difference between westerners and Japanese in the development of APTE. Our results will be available for establishing the prevention of APTE in medical patients in Japan. The Japanese Society of Pulmonary Embolism Research (JaSPER) study investigators are listed in the Appendix.     

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.     

Who should be tested for thrombophilia?

PURPOSE OF REVIEW: The purpose of this review is to identify on the basis of available data and expert opinions who would benefit most from screening for thrombophilia. RECENT FINDINGS: Recent studies have clearly defined the risk of venous thromboembolism in members of families with inherited thrombophilia. Meta-analyses have shown the role of the most common thrombophilic conditions in increasing the risk of recurrent venous thromboembolism in carriers. Screening for thrombophilia in venous thromboembolism patients might help identify those at higher risk of recurrences even though it is unclear how this information can be of use in modifying their management. Thrombophilia seems to play a role in early fetal losses as also shown in women at their first intended pregnancy, which makes it interesting to screen women after only one bad pregnancy outcome. SUMMARY: Screening for thrombophilia can be performed particularly in young patients with venous thromboembolism. Carriers of inherited thrombophilia are at increased risk of venous thromboembolism recurrences. Screening families of venous thromboembolism patients with thrombophilia allows the identification of still asymptomatic carriers who may benefit from thromboprophylaxis. This may be true of women in fertile age belonging to thrombophilic families. In thrombophilic women with pregnancy complications prophylaxis may be offered to prevent recurrences.     

Clinical characteristics of acute pulmonary thromboembolism in Japan: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research

BACKGROUND: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome have not yet been assessed in large series. HYPOTHESIS: The present study was designed to investigate the current status of APTE in Japan. METHODS: Of a total of 533 registry patients with pulmonary thromboembolism, 309 with APTE were analyzed with respect to clinical symptoms and signs, predisposing factors, diagnostic procedures, estimation of deep venous thrombosis, treatment, and clinical course. RESULTS: Main risk factors were recent major surgery, cancer, prolonged immobilization, and obesity; only a few patients had coagulopathy and 36% were in cardiogenic shock at presentation. The majority of registry patients underwent lung scans or pulmonary angiography; 30% were diagnosed only by lung scanning. Venous ultrasonography was used in only 34 patients, while 188 patients underwent at least one diagnostic procedure for deep venous thrombosis. Thrombolysis was more frequently performed in patients with cardiogenic shock, and only a few patients received thromboembolectomy. In-hospital mortality rate was 14%. In patients with cardiogenic shock, the mortality rate was reduced by thrombolysis. The predictors of in-hospital mortality were male gender, cardiogenic shock, cancer, and prolonged immobilization. CONCLUSIONS: The patients in this registry had almost the same findings as those in Western patients, except for some points that had the possibility of demonstrating a difference between Westerners and Japanese in the development of APTE. These results can prove especially helpful in planning prospective, randomized trials that will clarify the impact of widely used treatment modalities on the outcome of patients with APTE.     

Triggers of acute pulmonary thromboembolism developed in hospital, with focusing on toilet activities as triggering acts

BACKGROUND: The recognition of the trigger which is the action leading to the occurrence of acute pulmonary thromboembolism (APTE) is important to perform early diagnosis and early management of APTE. METHODS AND RESULTS: The trigger of APTE in 138 patients who developed APTE in hospital was investigated. The triggers of APTE were specified in 57 patients. Approximately half of these patients developed APTE during toilet activities (defecation and micturition). Mortality of the patients with APTE associated with toilet activities was 33%. APTE associated with toilet activities was independently related to a recent major surgery, heart diseases and a recent angiography. CONCLUSIONS: Defecation and micturition would be common triggers of APTE after operation and angiography, especially in patients with cardiac dysfunction.     

Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives

BACKGROUND: Conflicting data are available on air travel as a risk factor for venous thromboembolism. To our knowledge, there are no studies investigating whether individuals with thrombophilia and those taking oral contraceptives are more likely to develop venous thromboembolism during flights than those without these risk factors. PARTICIPANTS AND METHODS: The study sample consisted of 210 patients with venous thromboembolism and 210 healthy controls. DNA analysis for mutations in factor V and prothrombin genes and plasma measurements of antithrombin, protein C, protein S, total homocysteine levels, and antiphsopholipid antibodies were performed. RESULTS: In the month preceding thrombosis for patients, or the visit for controls, air travel was reported by 31 patients (15%) and 16 controls (8%), with an oddsratio of 2.1 (95% confidence interval, 1.1-4.0). Thrombophilia was present in 102 patients (49%) and 26 controls (12%), and oral contraceptives were used by 48 patients and 19 controls (61% and 27% of those of reproductive age, respectively). After stratification for the presence of air travel and thrombophilia, the odds ratio for thrombosis in individuals with both risk factors was 16.1 (95% confidence interval, 3.6-70.9). Stratification for the presence of air travel and oral contraceptive use gave an odds ratio of 13.9 (95% confidence interval, 1.7-117.5) in women with both risk factors. CONCLUSIONS: Air travel is a mild risk factor for venous thromboembolism, doubling the risk of the disease. When thrombophilia or oral contraceptive use is present, the risk increases to 16-fold and 14-fold, respectively, indicating a multiplicative interaction.     

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63·98%) and 191 patients (66·8%) had a thrombophilia marker. Eighty nine (46·6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61·8% of patients with high risk of VTE. Among them, 37·7% were treated in the third trimester only and 24·1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0·35%) and two postpartum-related VTE (0·7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0·35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.     

Association between antithrombotic treatments and prognosis of patients with acute pulmonary thromboembolism in Japan.

The utility of thrombolysis in patients with acute pulmonary thromboembolism (APTE) remains controversial, although anticoagulation therapy for APTE is well-established in Western countries. Nonetheless, large clinical trials of antithrombotic treatments for APTE have yet to be performed in Japan. In the present study, the association between antithrombotic treatments (thrombolysis and anticoagulation) and the clinical outcomes was retrospectively investigated in 225 APTE patients. In-hospital mortality was significantly lower in hemodynamically stable patients who received anticoagulation therapy than in those who received no adequate therapy (0% vs 33%). Thrombolysis in patients with or without cardiogenic shock failed to improve the in-hospital outcomes compared with those who received anticoagulation treatment (8% vs 3%). There was no significant difference in the bleeding rate between patients receiving thrombolysis and anticoagulation (3% vs 3%). These results indicate that anticoagulation could reduce the mortality of hemodynamically stable APTE patients and that the outcome after thrombolysis or anticoagulation treatment was similar. However, this study was limited because it was executed retrospectively. Further prospective randomized trials to investigate the efficacy of thrombolysis in Japan should be performed to completely address this issue.     

Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception

BACKGROUND: Unrecognized thrombophilic defects increase the risk of venous thromboembolism (VTE) in women during oral contraception (OC). We evaluated the sensitivity and specificity of a family history of VTE to identify thrombophilia in women before OC and after venous thrombotic complications during OC. METHODS: Thrombophilia screening was performed after obtaining a family history by means of a standardized questionnaire in (1) thrombosis-free women before OC and (2) women after an episode of VTE during OC. RESULTS: We evaluated 479 thrombosis-free women before OC (age range, 15-49 years); family history was positive in 49 (10.2%). Thrombophilic defects were identified in 36 participants (7.5%; 95% confidence interval [CI], 5%-10%), 3 of whom had a positive family history (8.3%). The sensitivity and positive predictive value of family history of thrombophilic defects were 8.3% (95% CI, 2%-22%) and 6.1% (95% CI, 1%-17%), respectively. We also evaluated 189 women after VTE complications during OC (age range, 15-49 years); family history was positive in 48 (25.4%; 95% CI, 19%-32%), 22 of whom had a thrombophilic defect (45.8%; 95% CI, 31%-61%). Thrombophilic defects were identified in 81 women (42.8%; 95% CI, 36%-50%). The sensitivity and positive predictive value of family history of thrombophilic defects were 27.2% (95% CI, 18%-38%) and 45.8% (95% CI, 31%-61%), respectively. CONCLUSION: Family history of VTE has low sensitivity and positive predictive value for identifying women with thrombophilia who are more susceptible to VTE complications during OC.     

Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population

Hereditary natural anticoagulant deficiencies are the major cause of genetic thrombophilia in Asia. Given the growing acknowledgment of the risk of venous thromboembolism in Asian populations, we investigated the frequency and mutation spectrums of natural anticoagulant deficiency in Korea. The group of patients consisted of consecutive patients with venous thromboembolism screened for thrombophilia. Genetic tests were performed on suspicion of natural anticoagulant deficiency. For the population group, >3,000 individuals were screened from routine check-ups, and those with a low level (<1^st percentile) of natural anticoagulant underwent genetic tests. Mutations were detected by direct sequencing of PROC, PROS1, and SERPINC1, followed by additional multiplex ligation-dependent probe amplification for PROS1 and SERPINC1 for dosage mutations. Among 500 patients screened, 127 were suspected of having a natural anticoagulant deficiency, and this was genetically confirmed in 71: protein C deficiency in 36 (50.7%), antithrombin deficiency in 21 (29.6%), and protein S deficiency in 14 (19.7%). Among 3,129 individuals from the population who were screened, the frequency of natural anticoagulant deficiency was ~1.0%: antithrombin deficiency 0.49%, protein C deficiency 0.35%, and protein S deficiency 0.16%. Two PROC mutations causing type I protein C deficiency were prevalent (Arg211Trp and Met406Ile in patients and Arg211Trp in the population). Two SERPINC1 mutations causing type II antithrombin deficiency, Arg79Cys and Ser158Pro, were prevalent in the population group. This is the first study on the genetic epidemiology of natural anticoagulant deficiencies in Korea. The results demonstrated that the frequencies and spectrum of mutations underlying genetic thrombophilia in Korea are different not only from those in Caucasians but also those in other Asian populations.     

Study of the echocardiographic diagnosis of acute pulmonary thromboembolism and risk factors for venous thromboembolism

OBJECTIVES: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE). METHODS: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group). RESULTS: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE. CONCLUSIONS: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.     

Clinical study of venous thromboembolism during pregnancy and puerperium

We encountered 16 cases of venous thromboembolism (VTE) in women during pregnancy and/or puerperium over the past 15 years at our perinatal center, representing 0.14% of all patients who delivered babies. The present study was undertaken to analyze the risk factors, clinical course and outcomes in these 16 cases. The ages of the patients varied from 29 to 39 years. Four women had pulmonary embolism (PE), 3 of which after caesarean section (C/S) at 35 to 40 weeks, and one case after ovarian cystectomy at 13 weeks of gestation. Twelve cases had deep venous thrombosis (DVT), 4 of which during pregnancy, and the remaining 8 cases after C/S. Four patients who had DVT during a normal course of pregnancy had severe thrombophilia: antiphospholipid antibody syndrome, a history of thrombosis and antithrombin (AT) deficiency. They were treated with heparin with or without AT and had healthy babies via successful vaginal deliveries. The common risk factors in 3 cases of PE with C/S was prolonged bed rest due to threatened premature delivery with total placenta previa, uterine myoma and Ehlers-Danlos syndrome. Other risk factors were massive bleeding, and positive lupus anticoagulant. However, the case of the ovarian cystectomy had only one risk factor, which was obesity. This patient died but the remaining patients recovered with treatment. Because of the low incidence of thrombosis in the Japanese population, prophylactic anticoagulant therapy has not routinely been given to patients undergoing obstetrical operations. However, proper management including prophylactic anticoagulant therapy might be considered for risk patients, depending on the risk factors.     

Thrombophilia: 2009 update

As venous thrombosis is mostly caused by disturbances in the plasma coagulation system, abnormalities of coagulation factors are mostly risk factors for venous thromboembolism (VTE). Relatively little is known about thrombophilias that predispose to arterial thromboembolism. Although some abnormalities in the fibrinolytic pathway appear to predispose to arterial thrombosis, the associations are weak and often inconsistent between studies. At present, there is not enough consistent and clinically meaningful information to include fibrinolytic parameters in a clinical thrombophilia workup. Controversy exists as to which patients and family members to test for thrombophilia. Several testing guidelines exist. Routine screening for inherited thrombophilias is not indicated in patients with VTE provoked by immobility, surgery, and malignancy, or in those with arterial thrombosis with arteriosclerosis risk factors. Heterozygous factor V Leiden (FVL) and prothrombin 20210 mutations increase the risk for recurrent VTE only slightly once anticoagulation is stopped. Therefore, decisions regarding the length of anticoagulant therapy typically are not influenced by finding one of these heterozygous mutations. The main reason to perform thrombophilia testing in a patient is to detect a strong thrombophilia (ie, antithrombin deficiency, antiphospholipid antibody syndrome, homozygous FVL, double-heterozygous FVL plus prothrombin 20210 mutation, protein C deficiency, and maybe protein S deficiency). The finding of a strong thrombophilia has several clinical consequences: it decreases the threshold to recommend long-term anticoagulation in a patient with unprovoked VTE; facilitates discussion regarding whether anticoagulant or antiplatelet therapy is the preferred empiric treatment for a patient who had an unexplained arterial, nonarteriosclerotic thromboembolic event; and leads to the consideration of testing asymptomatic female family members for the identified thrombophilia(s) so they can be counseled on their risk of thromboembolism, the use of hormonal therapies, and the potential benefit of pre- and postpartum anticoagulant therapy.     

Effectiveness and safety of the thrombolytic therapy for acute pulmonary thromboembolism: results of a multicenter registry in the Japanese Society of Pulmonary Embolism Research

OBJECTIVE: To assess the effectiveness and safety of thrombolytic treatment for acute pulmonary thromboembolism (APTE), especially in the hemodynamically stable patients with right ventricular afterload stress. METHODS AND RESULTS: In a total of 221 patients with APTE, the association between thrombolytic treatment and the clinical outcomes were investigated. Thrombolysis was given to 121 patients (Thrombolytic Group), and the remaining 100 patients were treated with anticoagulation alone (Anticoagulation Group). In both patients with prolonged shock and patients who were hemodynamically stable without right ventricular afterload stress, the rate of death and recurrence of APTE in Anticoagulation Group were similar to those in Thrombolytic Group. In patients with right ventricular afterload stress, better outcomes were observed in Thrombolytic Group than in Anticoagulation Group, although the difference did not reach statistical significance. There was no significant difference in the rate of major bleeding episode between these two groups. CONCLUSION: Our results suggested that performing thrombolytic treatment in APTE patients with right ventricular afterload stress should be considered even in Japan.     

Thrombophilic dimension of recurrent fetal loss in Indian patients

We studied the prevalence of acquired and genetic thrombophilia in 198 women with recurrent fetal loss who were having three or more than three abortions. Seventy-nine women had only early pregnancy losses, that is, first trimester abortions, 30 women had only late pregnancy losses, that is, second and third trimester abortions whereas 89 had both early and late pregnancy losses. The control group included 100 age-matched fertile parous women who did not have any obstetric complications and had at least one normal healthy child. Several genetic and acquired thrombophilia markers were studied. The strongest association was observed with anticardiolipin (odds ratio 22.6, confidence interval 5.7-89, P = 0) followed by lupus anticoagulant, anti-beta2 glycoprotein-1, antiannexin. Association of antiphospholipid antibody syndromes was detected with the time of pregnancy loss in anticardiolipin, lupus anticoagulants, which was significantly associated with early pregnancy loss as compared with second and third trimester loss. In case of beta2 glycoprotein-1, antiannexin it was less significantly associated with early pregnancy loss as compared with second and third trimester loss. The risk of fetal loss with protein S deficiency was the highest risk observed for any heritable thrombophilia, followed by protein C, factor V Leiden, endothelial protein C receptor, antithrombin III deficiency and beta448 fibrinogen polymorphism. Modest risks were also observed with 5,10-methylenetetrahydrofolate reductase, plasminogen activator inhibitor 4G/4G polymorphisms and beta448 fibrinogen polymorphism. A combination of two or more than two genetic risk factors were observed in 55 (27.7%), whereas the genetic and acquired risk factors were observed in 107 (54%) of the cases. Thrombophilia is an important contributing factor for both early and late pregnancy losses; approximately two-thirds of our cases of unexplained fetal losses could be explained by acquired or heritable thrombophilia or both, which is in line with other western studies.     

Evidence-based indications for thrombophilia screening

Thrombophilic defects have been shown to be associated with an increased risk of venous thrombosis, fetal loss, and gestational complications. The knowledge about the clinical relevance of thrombophilic defects is increasing, and evidence-based indications for thrombophilia screening are therefore discussed in this review. Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism is more cost-effective than universal screening in all patient groups evaluated. In the majority of patients with acute venous thrombosis, the results of thrombophilia screening do not influence the duration of oral anticoagulation. The only patient population who clearly profits from thrombophilia screening in this situation are patients with a newly diagnosed antiphospholipid syndrome, because prolonged anticoagulation can avoid the high incidence of recurrence in this patient population. Because of the increased risk of venous thrombosis during pregnancy and the puerperium, thrombophilia screening is indicated in selected patients with a previous history of venous thrombosis or a positive family history. Significant associations with early and late pregnancy loss are observed for carriers of the heterozygous factor V Leiden mutation, the heterozygous prothrombin-mutation G20210A and anticardiolipin antibodies, while protein S deficiency is significantly associated with late pregnancy loss. Antithrombotic drugs like UFH, LMWH or low-dose aspirin may have a potential therapeutic benefit in patients with recurrent pregnancy loss and thrombophilia, but placebo-controlled, multicenter trials are urgently needed to clarify this issue. Although a supra-additive effect for the risk of venous thrombosis is observed between oral contraceptives and some thrombophilias, the absolute incidence of venous thromboembolism is low in premenopausal women and mass screening strategies are therefore unlikely to be effective. While antiphospholipid antibodies are known to be associated with arterial thrombosis, screening for heritable thrombophilias is not useful in arterial thrombosis, although subgroup analysis indicates that they may play a role particularly in young patients and children.     

Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.     

Clinical features of acute pulmonary thromboembolism in younger patients.

The incidence of acute pulmonary thromboembolism (APTE) in younger patients is extremely low compared with older patients, so the clinical features of these younger patients with APTE is unknown. In the present study, 8 patients with APTE who were less than 40 years old (YG) were compared with 40 patients who were more than 41 years of age (OG). All YG patients had coagulopathy compared with 3 patients in the OG (p<0.01). Deep venous thrombosis (DVT) occurred in all 8 patients in the YG compared with 19 patients in the OG (p<0.01). A higher incidence of patients whose symptoms occurred gradually was noted in the YG (p<0.05). There were no significant differences in clinical characteristics, initial symptoms, past history or other predisposing factors for venous thromboembolism between the 2 groups. Residual pulmonary hypertension was not noted in the YG. However, 1 patient in the YG had recurrent APTE, despite good warfarin control. This study demonstrated the frequency of gradual onset, coagulopathy and clinical signs of DVT in the YG and therefore more careful and long-term observation is necessary in such patients.     

Inherited thrombophilia, pregnancy, and oral contraceptive use: clinical implications

Inherited thrombophilia has been reported to be associated with an increased risk for complications of pregnancy, including venous thromboembolism (VTE) as well as preeclampsia (PEC), fetal loss (FL), fetal growth retardation (FGR), and abruptio placentae (AP), the latter probably due to inadequate placental perfusion. The estimate of risk largely depends on the kind of thrombophilia and on the criteria applied for the selection of the patients, producing in some cases contradictory results. Convincing evidence is available that deficiency of antithrombin III (AT), protein C (PC), and protein S (PS) is a risk factor for VTE and late FL. Factor V (Leiden) is associated with an increased risk for VTE, unexplained recurrent FL, late FL, and perhaps PEC; prothrombin G20210A is a weak risk factor for VTE. So far, the data available for FGR and AP are scarce. However, the absolute risk for VTE during pregnancy and puerperium is between 1 and 3%, in comparison with the baseline risk of 0.08%. Antithrombotic prophylaxis with subcutaneous heparin is warranted during puerperium in all women with thrombophilia and throughout all pregnancy in women at higher risk (AT deficiency, homozygosity for factor VLeiden, and perhaps PC and PS deficiencies); treatment with subcutaneous heparin for prevention of FL among women with thombophilia is under investigation. Presence of inherited thrombophilia increases the risk for VTE due to oral contraceptives up to an absolute risk of 3 per 1000 person-years, in comparison with the baseline risk of 3 to 6 per 10000 person-years; the risk is further increased by first usage, the use of preparations containing third-generation progestins, and thrombophilia due to AT, PC, and PS deficiency as well as homozygous factor V (Leiden) and combined defects.