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Diagnostic imaging in deep vein thrombosis of the limbs.

The clinically suspected deep vein thrombosis (DVT) should always be confirmed by instrumental procedures. In fact, about 70% of patients with clinically suspected DVT are shown to be negative on instrumental investigations. Phlebography is still the gold standard in the diagnosis of peripheral DVT. Main phlebographic findings are: persistent filling defect; abrupt interruption of contrast in a vein; lack of opacification in all or some deep veins; flow diversion with opacification of collateral branches. At present, peripheral phlebography is performed when the other noninvasive exams (Color Doppler US and Duplex Doppler) are doubtful, technically limited or when thrombosis of innominate veins or superior vena cava, is suspected. Real-time US enables direct visualization of the limb proximal veins. The venous wall, the venous valves, the thrombus and its development, the anatomic variants, the perivenous structures which may impact on the normal physiology of venous return, are depicted. However, the distal veins of the leg and arm and deep veins (the iliac veins, the superficial femoral vein in the adductor canal) are not accurately visualized. The US findings in DVT include: the presence of echoes within the vascular lumen; the veins in axial scans are not compressible. Pulsed Doppler and duplex Doppler combine the morphologic and functional study. Injury caused by DVT at the valvular level (postphlebitic syndrome) is visualized. Primary deep vein thrombosis caused by valvular disorders (valvular aplasia) is identified. Inadequate superficial and perforating veins to be treated with surgery are mapped. Color Doppler US depicts directly superficial and deep limb veins combining the morphologic with the functional assessment represented by the visualization of the map of flow velocity and direction. Recently, a new diagnostic procedure, the color Doppler Energy (CDE) or Power Doppler has been introduced. Together with mean flow velocity and spectral variance, the signal energy or power is also analyzed. The CDE is independent of the US incidence angle, it does not shows the flow direction, detects particularly slow flows, early canalization of thrombi and non occlusive thrombosis. Color Doppler diagnosis of thrombosis is prompt because an area with absence of color is visualized. Collateral vessels and flow direction within them, is well depicted. Beside the site and extension of thrombosis, color Doppler US is able to directly visualize the distal end of the thrombus, which when floating is at high risk for embolism. CT allows an adequate study of the iliocaval axis and is useful if phlebography or color Doppler US are not diagnostic. Iliocaval thrombosis represents a not infrequent finding during abdominal CT. The thrombus appears as a hypodense mass encircled by the hyperdense rim of contrast medium.

Humans↗

The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis.

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.

Adolescent↗

The methylenetetrahydrofolate reductase TT677 genotype is associated with venous thrombosis independently of the coexistence of the FV Leiden and the prothrombin A20210 mutation.

A polymorphism, C-->T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for venous thrombosis. We have investigated the frequency of the TT genotype in 277 consecutive patients with confirmed deep venous thrombosis and 431 healthy subjects. The TT MTHFR genotype was more frequent in patients than in controls (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis among carriers of this genotype was significantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factors for venous thrombosis. Factor V Leiden and prothrombin G-->A20210 are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A20210 mutations, a significant association was also observed. After adjustment for sex, FV Leiden and prothrombin A20210 mutation, the estimated risk of venous thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.

Adolescent↗

Thrombosis during pregnancy and the postpartum period.

OBJECTIVE: To describe the circumstances surrounding deep vein thrombosis among pregnant or postpartum patients enrolled in a large multicenter registry. STUDY DESIGN: Consecutive patients with ultrasound-confirmed deep vein thrombosis were enrolled at 183 institutions during a 6-month period from October 2001 to March 2002. Fifty-three who were either pregnant or within 6 weeks postpartum were analyzed. RESULTS: Thirty-four were pregnant and 19 were postpartum. Among those pregnant, 44% experienced deep vein thrombosis in the first trimester, 24% in the second, and 26% in the third. Deep vein thrombosis occurred in the left lower extremity in 76% of the pregnant and 47% of the postpartum women. Four pregnant and 2 postpartum women had pelvic vein thrombosis. Among those postpartum, 74% had undergone surgery within 3 months. CONCLUSION: During pregnancy, the risk of deep vein thrombosis begins in the first trimester. Thus, we believe that when prophylaxis is indicated, it should be initiated early in gestation.

Adult↗

Estrogens, progestogens and thrombosis.

Hundreds of millions of women worldwide use either oral contraceptives or postmenopausal hormone replacement. The use of oral contraceptives leads to an increased risk of venous thrombosis, of myocardial infarction, of stroke and of peripheral artery disease, the risks of which are highest during the first year of use. Women with coagulation abnormalities have a higher risk of venous thrombosis when they use oral contraceptives (or postmenopausal hormones) than women without these abnormalities. The risk of venous thrombosis is also higher for preparations containing desogestrel or gestodene (third-generation progestogens) than for those containing levonorgestrel (second-generation progestogens). A previous thrombosis as well as obesity also increase the risk of oral contraceptive-related thrombosis. Hormone replacement therapy increases the risk of venous thrombosis, and has no beneficial, and possibly even a detrimental, effect on the risk of arterial disease. The risk of arterial disease in oral contraceptive users and users of hormone replacement therapy is at most weakly affected by the presence of prothrombotic abnormalities.

Contraceptives, Oral↗

von Willebrand factor and factor VIII as risk factors for arterial and venous thrombosis.

Since the early 1990s attempts have been made to elucidate whether high concentrations of von Willebrand factor (VWF) and factor VIII (FVIII) in plasma are associated with an increased risk of thrombosis. Several prospective studies on the role of VWF in arterial thrombosis, mainly coronary heart disease, were performed in healthy individuals and patients with previous cardiovascular disease. Although the majority showed an association between high VWF levels and arterial thrombosis, others failed to confirm such findings. A smaller number of studies have evaluated FVIII, mainly for its association with venous thrombosis. Two prospective observations, together with several case-control studies, provided solid evidence of an association between high FVIII levels and a first or recurrent episode of venous thrombosis. On the whole, high levels of VWF and FVIII in plasma confer a moderately high risk of arterial and venous thrombosis, respectively. These findings have no therapeutic implication, but they should be taken into account in the assessment of the individual risk profile.

Animals↗

Cortical vein thrombosis misinterpreted as intracranial haemorrhage in severe ovarian hyperstimulation syndrome: case report.

A case of cortical vein thrombosis presenting as intracranial haemorrhage is described in a patient with ovarian hyperstimulation syndrome (OHSS) after IVF and embryo transfer. Veno-occlusive disease of the brain could appear as a haemorrhagic lesion on magnetic resonance imaging (MRI) and this made the initial diagnosis of cortical vein thrombosis difficult. The patient developed deep vein thrombosis 2 weeks after the intracranial event and the diagnosis of cortical vein thrombosis was made at that time on MRI study after the resolution of the haemorrhage. This patient actually developed generalized thrombosis as a complication to OHSS. Although the initial MRI picture may be misleading, the diagnosis of thrombosis should always be kept in mind, as it is the commonest cause of intracranial lesions after OHSS.

Adult↗

Coronary thrombosis in non-cardiac death.

BACKGROUND: Coronary thrombosis is the major cause of acute myocardial ischaemia but can be, albeit rarely, clinically silent. We investigated a series of autopsy hearts from hospitalized patients who died from non-cardiac causes, to detect and study coronary thrombosis. METHODS: The series consisted of 132 autopsy cases (81 men and 51 women, age range 32-39 years, mean 63 +/- 14), in whom cause of death was confirmed as extracardiac. Major epicardial coronary arteries were isolated from the hearts and routinely processed for histopathological study. We evaluated the presence of coronary atherosclerosis and thrombosis. Plaque size was histologically graded with low magnification lenses. RESULTS: Coronary atherosclerosis, which was found in 110 hearts, caused critical stenosis or occlusion of at least one major vessel in 55 (41.6%) cases. Coronary thrombosis was found in 10 vessels from nine different hearts. One coronary tree presented two thrombi in two different vessels. Thrombi were mural in all but one vessel. We did not observe either deep sub-thrombotic ulceration or atheromatous material mixed with thrombus. Deep thrombus layers often presented organizing features. There was no correlation between thrombosis and degree of vessel stenosis, which was only mildly increased by thrombus. Plaque rupture without thrombus was found in five coronary arteries of five different cases. CONCLUSIONS: Coronary thrombus may overlay the intima of a diseased vessel independently of plaque type and severity. Moreover, thrombosis is more frequent than expected, although it is rare when compared with the spread of coronary atherosclerosis. It may represent a plaque progression mechanism in the natural history of coronary atherosclerosis.

Adult↗

Randomized controlled trial of clopidogrel plus aspirin to prevent hemodialysis access graft thrombosis.

Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.

Aged↗

Low-molecular-weight heparin (dalteparin) effectively prevents thrombosis in a rat model of deep arterial injury.

Unfractionated heparin is often used to prevent thrombosis in microvascular surgery, but a major drawback of heparin therapy is increased bleeding. Low-molecular-weight heparins prevent venous thrombosis as effectively as heparin and have better bioavailability and a longer plasma half-life, which explains the increased use of low-molecular-weight heparins as substitutes for heparin in clinical practice. However, the ability of low-molecular-weight heparins to prevent arterial thrombosis has been debated. In this study, the authors compared the antithrombotic and antihemostatic effects of heparin and the low-molecular-weight heparin dalteparin in a rat model of arterial thrombosis. A segment of the left common carotid artery was isolated between vascular clamps and opened longitudinally. An endarterectomy was performed and the arteriotomy was closed with a running suture. The antithrombotic effect (vascular patency 31 minutes after reperfusion) and the surgical bleeding were measured. Groups of 10 rats were treated in a blind, random fashion with intravenous injection of one of the following substances 1 minute before clamp release. Three groups received a bolus of heparin (20, 60, or 180 IU anti-factor Xa/kg), three groups received dalteparin (60, 180, or 540 IU anti-factor Xa/kg), and one group was treated with vehicle (saline). Heparin 180 IU/kg produced a distinct antithrombotic effect compared with the control group (p = 0.03), but it also significantly increased the surgical bleeding to 2.0 g compared with 1.5 g in the control group (medians, p = 0.01). Dalteparin 180 and 540 IU/kg also produced a powerful antithrombotic effect (p = 0.01 and p = 0.03, respectively). In contrast to heparin, 180 IU/kg dalteparin did not increase the surgical bleeding (median, 1.5 g; p = 0.37 versus controls). Dalteparin 540 IU/kg increased the median surgical bleeding to 2.6 g (p = 0.06 versus controls). The nonsignificant difference may be explained by the great interindividual variation of surgical bleeding in the high-dose dalteparin group. Dalteparin prevented arterial thrombosis as effectively as unfractionated heparin. In contrast to heparin, dalteparin did not increase the surgical bleeding, which indicates that dalteparin instead of heparin can be used to prevent thrombosis in microvascular surgery.

Animals↗

Integrative Multi-Omics Analysis Identifies Thrombosis-Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer.

Emerging evidence indicates that coagulation-related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis-associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis-associated genes and establish a machine learning-based prognostic signature. Genome-wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome-wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility-associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single-cell RNA sequencing (scRNA-seq) and cell-cell communication analyses were further performed to characterize cell-type-specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis-associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high- and low-risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility-associated transcriptional programs that were positively correlated with the thrombosis-associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA-seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil-B cell interactions involving COLLAGEN-related signaling. This integrative multi-omics study identified a thrombosis-associated molecular signature linked to prognosis and germline susceptibility-associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single-cell analysis suggested potential immune-related communication features.

Humans↗

Recanalisation of cerebral venous thrombosis.

OBJECTIVE: To investigate recanalisation in the first 12 months after cerebral venous thrombosis. METHODS: 33 consecutive patients presenting with cerebral venous thrombosis were enrolled in the study. Diagnosis was made by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or catheter angiography. Patients were initially treated with intravenous heparin. Warfarin was given for at least four months. Cerebral MRI and MRV were done at four months and repeated after 12 months if venous thrombosis persisted. Outcome was evaluated by the Rankin scale at 12 months. RESULTS: Outcome at 12 months was good, with a median modified Rankin scale score of 0 (range 0 to 2); 27 patients (82%) had no residual deficits. No patient suffered recurrent cerebral venous thrombosis, deep vein thrombosis, or pulmonary embolism during follow up. After four months, all deep cerebral veins and cavernous sinuses, 94% of superior sagittal sinuses, 80% of straight sinuses, 73% of jugular veins, 58% of transverse sinuses, and 41% of sigmoid sinuses had recanalised. No further recanalisation was observed thereafter. CONCLUSIONS: The results suggest that recanalisation only occurs within the first four months following cerebral venous thrombosis and not thereafter, irrespective of oral anticoagulation.

Adult↗

Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation.

The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.

Blood Circulation↗

[A family with multiple thrombosis including infancy occurrence].

Since the first patient with antithrombin deficiency was reported, various hereditary thrombophilia have been discovered. However, we experienced a family line of multiple thrombosis in which known hereditary thrombophilia were all refuted. Case 1 died of inferior vena cava thrombosis at the age of 56 days. Case 2, the elder sister of Case 1, developed deep vein thrombosis of the left leg at age 2. She was started on warfarin but contracted deep vein thrombosis of the right leg at the age of 7. In the family of these cases there have been another five cases of thrombosis, spanning three generations, giving a total of seven cases. Six of the cases developed at an early age, below 50 years. Antithrombin, protein C, protein S, heparin cofactor II, soluble thrombomodulin, plasminogen, alpha 2 plasminogen inhibitor, and tissue factor pathway inhibitor were measured but there were no abnormalities, nor was there any resistance to activated protein C. The onset of thrombosis in this family is becoming younger with the passing of generations, and clinical symptoms have been showing a worsening tendency.

Age Factors↗

Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice.

Occlusive thrombosis depends on the net balance between platelets, coagulation, and fibrinolytic factors. Epidemiologic information suggests that plasminogen activator inhibitor-1 (PAI-1), a central regulator of the fibrinolytic system, plays an important role in determining the overall risk for clinically significant vascular thrombosis. Vitronectin (VN), an abundant plasma and matrix glycoprotein, binds PAI-1 and stabilizes its active conformation. This study assessed the role of PAI-1 and VN expression in the formation of occlusive vascular thrombosis following arterial or venous injury. The common carotid arteries of 17 wild-type (WT) mice and 8 mice deficient in PAI-1 were injured photochemically while blood flow was continuously monitored. WT mice developed occlusive thrombi at 52.0 +/- 3.8 minutes (mean +/- SEM) following injury; mice deficient in PAI-1 developed occlusive thrombosis at 127 +/- 15 minutes (P <.0001). Mice deficient in VN (n = 12) developed vascular occlusion 77 +/- 11 minutes after injury, intermediate between the values observed for WT mice (P <.03) and mice deficient in PAI-1 (P <.01). PAI-1 and VN also affected the time to occlusion after injury to the jugular vein. Three WT mice developed occlusive venous thrombosis an average of 39.7 +/- 1 minutes following the onset of injury, whereas the jugular veins of 4 mice deficient in PAI-1 and 4 deficient in VN occluded 56.7 +/- 5 and 58.7 +/- 2 minutes, respectively, following injury (P <.04 and P <.01 compared to WT mice). These results suggest that endogenous fibrinolysis and its regulation by PAI-1 and VN have important roles in the development of occlusive vascular thrombosis after vascular injury. (Blood. 2000;95:577-580)

Animals↗

The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor, in rat models of venous and arterial thrombosis.

The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor (Ki = 4.9 nM) was evaluated in rat models of venous thrombosis combined with a bleeding time test and arterial thrombosis. After drugs were given by i. v. bolus injection plus a continuous infusion, the ID50, (a dose that exhibits 50% inhibition of thrombus formation over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.04 mg/kg plus 0.04 mg/kg/h, 0.1 mg/kg plus 0.4 mg/ kg/h, and 13.0 IU/kg plus 26.0 IU/kg/h, respectively, in the venous thrombosis study. The BT2 (a dose that causes 2-fold prolongation of bleeding time over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.9 mg/kg plus 0.9 mg/kg/h, 1.0 mg/kg plus 0.6 mg/kg/h, and 345.5 IU/kg plus 691.0 IU/kg/h in the rat tail transection model. The ratios of BT2/ID50 of AT-1459, argatroban, and dalteparin were 22.5, 10.0, and 26.6, respectively. In a rat model of arterial thrombosis induced by topical FeCl2 application, intravenous administration of AT-1459, argatroban, and dalteparin improved the vessel patency significantly (P < 0.01) at 0.6 mg/kg plus 0.6 mg/kg/h, 0.6 mg/kg plus 2.4 mg/kg/h, and 300 IU/kg plus 600 IU/kg/h, respectively. The oral antithrombotic effect of AT-1459 lasted for 6 after administering 30 mg/kg and improved the vessel patency significantly 1 h after administering the same dose in venous and arterial thrombosis models, respectively, with a rapid onset of action. Warfarin also inhibited thrombus weight and improved the vessel patency significantly after oral administration of 0.3 mg/kg for three consecutive days in the same study. The antithrombotic and hemorrhagic effects of all drugs studied were correlated with plasma concentration or clotting times. These results suggest that AT-1459 may be clinically useful as an orally available antithrombotic agent for the prevention of venous and arterial thrombosis.

Administration, Oral↗

[P-pills and thrombosis].

This review provides an account of the present situation as reflected by findings in recent studies, which illustrate epidemiological, clinical and metabolic aspects of thrombosis associated with oral contraceptive (OC) usage. With the reduction of the oestrogen content of OCs, the relative risk for acute myocardial or cerebral thrombosis is now 1.5-3. Low-dose OCs containing third generation gestagens seem to be associated with less risk of infarction, and possibly of cerebral thrombosis, than are OCs containing second generation gestagens. The risk of venous thrombosis is increased 2-4-fold in conjunction with the usage of low-dose OCs with second generation gestagens, and possibly slightly more (3-5-fold) in conjunction with OCs containing third generation gestagens, though this is of small clinical significance. When prescribing OCs for women at an increased risk of venous thrombosis, a low-dose pill with a second generation progestagen seems to be preferable. If OCs are prescribed to women at an increased risk of arterial thrombosis, OCs with third generation progestagens seem to be a reasonable first choice. Women with no thrombotic predisposion can safely use any type of low-dose OCs [corrected].

Contraceptives, Oral, Hormonal↗

Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5.

BACKGROUND: Prolonged anticoagulation is the treatment of choice for patients with thrombosis and the antiphospholipid syndrome. However, there is still debate about the optimum intensity of anticoagulation. METHODS: The study included 66 patients with antiphospholipid syndrome (Sapporo criteria) and previous thrombosis. All were receiving oral anticoagulation to a target international normalized ratio of 3.5. Every patient was individually interviewed to recall major bleeding and thrombotic episodes during the previous 12 months. RESULTS: Patients were mainly women and white. The rate of major bleeding was 6 cases per 100 patient-years (95% confidence interval [CI] 1.6-15.0). The rate of intracranial bleed was 1.5 per 100 patient-years (95% CI, 0.04-8.4). None of the bleeding episodes was fatal. The rate of thrombotic recurrences was 9.1 cases per 100 patient-years (95% CI, 3.3-19.6). Most recurrences took place in the same vascular bed as the original thrombosis. Age, time receiving anticoagulant therapy, primary vs secondary antiphospholipid syndrome, positivity for anticardiolipin antibodies, positivity for lupus anticoagulant, previous arterial thrombosis, previous stroke, previous venous thrombosis, and previous thrombocytopenia were not predictive of bleeding events. However, the risk of thrombotic recurrences was independently higher in patients who were receiving anticoagulation for longer periods. CONCLUSIONS: The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses.

Adolescent↗