Internal jugular vein thrombosis after ovarian stimulation

Thromboembolic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. Here, we report a case of internal jugular vein thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or hereditary hypercoagulability. Screening for these risk factors in our patient was negative. The patient was successfully treated with low molecular weight heparin and a twin pregnancy is ongoing.     

Subclavian vein thrombosis following IVF and ovarian hyperstimulation: a case report

Thromboembolic phenomena are a serious consequence of assisted reproductive technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7 weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three weeks after recovering from OHSS, the patient presented with left neck pain and swelling. Ultrasound revealed a thrombus in the left jugular vein and left subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom resolution within 1 week. The patient remained on LWMH throughout her pregnancy and delivered at term. A literature review showed 97 published cases of thromboembolism following ovulation induction. A majority of these cases was associated with OHSS and pregnancy and the site of involvement was predominantly in the upper extremity and neck. Infertility physicians and obstetricians should be aware of this complication and keep in mind that it may occur weeks after resolution of OHSS symptoms.     

Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis.

Acute deep-vein thrombosis is usually treated with intravenous heparin for a number of days, then with oral anticoagulants for weeks to months. We have compared adjusted-dose warfarin sodium with fixed low-dose subcutaneous heparin in the prevention of recurrent deep-vein thrombosis. Sixty-eight patients with acute deep-vein thrombosis confirmed by venography were treated with intravenous heparin and then randomized to secondary prophylaxis. Nine of 35 patients receiving subcutaneous heparin, but none of 33 receiving warfarin sodium, had new episodes of objectively documented venous thromboembolism (P = 0.001). Seven patients on warfarin sodium experienced bleeding complications (of which four were major), as compared with no patients receiving subcutaneous heparin (P less than 0.005). Thus, adjusted-dose warfarin sodium is more effective than low-dose subcutaneous heparin in preventing recurrent venous thromboembolism, but its use is accompanied by a significant risk of bleeding.     

Heparin induced platelet aggregation: in vitro confirmation of thrombotic complications associated with heparin therapy

Eleven patients who developed thromboembolic complications while receiving heparin were studied for a possible adverse reaction to heparin as the cause of their progressive thrombosis. Fifteen additional patients who were receiving heparin for recurrent thromboembolism, but who did not develop signs of thrombotic complications, were studied as patient controls. The most significant finding was an abnormal in vitro aggregation response to heparin alone in all of the patients who developed complications who were tested for it (64 percent). None of the patient controls demonstrated this abnormality. In addition, thrombocytopenia was noted in all of the former but in only one of the latter. Results of prothrombin times, fibrinogens and fibrin split products eliminated disseminated intravascular coagulation as the cause of the thrombocytopenia in the majority of cases. Finally, an approach to the early detection of the abnormal heparin response is presented and guidelines for its therapeutic management are recommended.     

Internal jugular vein thrombosis caused by resistance to activated protein C as a complication of ovarian hyperstimulation after in-vitro fertilization

We present a case of a 24 year old woman who became pregnant(twins) after human menopausal gonadotrophin (HMG)-induced ovarianstimulation, in-vitro fertilization (IVF) and subsequent embryotransfer. She developed a right internal jugular vein thrombosisas a complication of severe ovarian hyperstimulation syndrome(OHSS) 28 days after embryo transfer. The thrombosis developedin spite of anticoagulation with low-dose heparin. Later a resistanceto activated protein C (APC) or Dahlbäck disease was diagnosed.Due to a new test procedure (accelerin inactivation test), thediagnosis was possible even under anti-coagulation treatment.The coincidence of hyperstimulation and internal jugular veinthrombosis with the concurrent diagnosis of resistance to APChas not been published previously. The benefit of general screeningfor resistance to APC before admission to the IVF programmeshould be weighed. Targeted selection of a group of high-riskwomen would therefore be made possible.     

Complications of IVF and ovulation induction

BACKGROUND: The frequency and importance of complications of IVF and other ovulation induction (OI) are poorly known. We examined the occurrence of serious complications and miscarriages leading to hospitalization or operation after IVF (including microinjections and frozen embryo transfers) and OI treatment (with or without insemination). METHODS: Women who received IVF (n = 9175) or OI treatment (n = 10 254) 1996-1998 in Finland were followed by a register linkage study until 2000. RESULTS: After the first IVF treatment cycle, 14 per 1000 women had a serious case of OHSS (ovarian hyperstimulation syndrome), with 23 per 1000 throughout the study period (mean of 3.3 treatments). The corresponding values after OI were very low. The rates of registered ectopic pregnancies and miscarriages after IVF were nine and 42 respectively per 1000 women, with corresponding rates after OI of eight and 42. Infections and bleeding were not common after IVF and even rarer after OI. Overall, 15% of IVF and 8% of OI women had at least one hospital episode during the study period. CONCLUSIONS: Though there was a low risk of complications after each IVF treatment cycle, repeated attempts resulted in serious complications for many women, and these occurred much more often than after ovulation induction alone.     

Thromboembolism after ovarian stimulation: successful management of a woman with superior sagittal sinus thrombosis after IVF and embryo transfer: case report

The current literature was reviewed in order to analyse the clinical manifestations, progression and management, and pregnancy outcome of thromboembolism in infertile patients undergoing ovarian stimulation. The first case of superior sagittal sinus thrombosis following IVF that was successfully managed with intracranial thrombectomy is also reported. This retrospective cohort study comprised 65 women who experienced thromboembolism after ovarian stimulation (64 from other published studies and the present case report). Thrombosis attack occurred at a mean (+/-SD) of 25.5 +/- 20.1 days after oocyte retrieval. The onset timing in the intracranial thrombosis group (10.2 +/- 4.6 days) was less (P < 0.05) than in those experiencing thromboembolism at other sites. Ovarian hyperstimulation syndrome (OHSS), haemoconcentration and high serum estradiol level were noted in 79, 62 and 54% of women respectively. Forty-eight of 55 patients (87%) who received anticoagulation recovered without sequelae. Among patients willing to continue pregnancy, 32% succeeded in term delivery with all healthy babies, and 23% were ongoing pregnancies. In conclusion, ovarian stimulation cycles accompanying high serum estradiol levels, haemoconcentration or OHSS are at potential risk of thromboembolism. Dose-adjusted heparinization is recommended as the first-line treatment of choice, while intravascular thrombolysis or operative thrombectomy is an aggressive but effective treatment. Continuation of pregnancy is considered safe, without any increased risk of fetal congenital anomalies.     

The incidence of major clinical complications in a Dutch transport IVF programme

Four different major clinical complications were identifiedin a retrospective analysis of 2495 in-vitro fertilization (IVF)cycles resulting in oocyte retrieval. The severe form of ovarianhyperstimulation syndrome (OHSS) occurred in 18 patients, givinga prevalence for this complication of 0.7%. Seven (39%) of these18 patients had previously been diagnosed as having polycysticovaries. Eleven patients were admitted with moderate OHSS. Adnexaltorsion was diagnosed in two patients. Ovariectomy was considerednecessary in both cases. Complications of the transvaginal procedureoccurred in seven cases (0.3%): one patient had an acute appendicitiswith puncture holes in the appendix, six patients were admittedshortly after oocyte retrieval with a pelvic inflammatory disease.Of the 624 pregnancies obtained, 13 were ectopic, giving anectopic pregnancy rate of 2.1%. It is concluded that seriousclinical complications of IVF treatment are rare. However, patientsshould be counselled for the occurrence of serious procedure-relatedcomplications before entering an IVF programme.     

A clinician's response to the oral contraceptive thrombosis controversy

The controversy involving new progestin oral contraceptives (OC) began in late 1995, continued through 1996, and started to reach resolution in 1997. The fundamental question is whether OC containing desogestrel and gestodene have a different risk of thrombosis compared with OC containing older progestins. Correcting for preferential prescribing and the healthy user effect leads to the conclusion that all low-dose OC--regardless of progestin type--have an increased risk of venous thromboembolism. Low-dose OC do not increase the risk of myocardial infarction or stroke in healthy, non-smoking women less than 35 years of age. With effective patient screening for risk factors, the serious side effects of OC can be virtually eliminated.     

Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group

BACKGROUND: Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. METHODS: We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. RESULTS: Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episode of thrombosis that was associated with a temporary risk factor. Among the 51 women with abnormal laboratory results or a previous episode of idiopathic thrombosis, or both, 3 (5.9 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 1.2 to 16.2 percent). CONCLUSIONS: The risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.     

严重髂股静脉血栓形成解剖因素及临床治疗

目的:探讨髂股静脉血栓形成的解剖因素及Fogarty导管取栓术并发症的防治。方法:对20例严重下肢深静脉血栓形成的病人,Fogarty取栓导管分别取出血管的血栓时,用肝素盐水冲洗或注入尿激酶24ku冲洗溶解残留血栓碎屑。结果:均自髂股、股浅、股深静脉取栓成功。随访0.5～3年17例肢体完全或基本恢复正常,有效率85％。结论:髂股静脉血栓形成与静脉行程长、易受压等解剖特点有关。Fogarty导管取出严重型静脉血栓是一种有效安全的方法;应用肝素冲洗或注入尿激酶可有效的清除残余血栓碎屑;松解受压血管可减少术后并发症。     

Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.

BACKGROUND. Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. METHODS. In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. RESULTS. Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049). CONCLUSIONS. Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.     

Uro-retroperitoneum after ultrasound-guided transvaginal follicle puncture in an oocyte donor: a case report

Ultrasound-guided transvaginal follicle aspiration is the standard technique for oocyte retrieval prior to IVF. Complications are rare, but some are potentially serious. We report a case of ureteral injury with acute-onset uro-retroperitoneum in a volunteer oocyte donor. The patient recovered rapidly after ureteral stenting. This case underlines the need for all candidate oocyte donors to receive proper information on serious procedure-related complications.     

Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis

We performed a randomized double-blind trial comparing continuous intravenous heparin with intermittent subcutaneous heparin in the initial treatment of 115 patients with acute proximal deep-vein thrombosis. Intermittent subcutaneous heparin as administered in this trial was inferior to continuous intravenous heparin in preventing recurrent venous thromboembolism. The subcutaneous heparin regimen induced an initial anticoagulant response below the target therapeutic range in the majority of patients and resulted in a high frequency of recurrent venous thromboembolism (11 of 57 patients, 19.3 percent), which was virtually confined to patients with a subtherapeutic anticoagulant response. In contrast, continuous intravenous heparin induced a therapeutic anticoagulant response in the majority of patients and a low frequency of recurrent events (3 of 58 patients, 5.2 percent; P = 0.024); the recurrences were limited to patients with an initial subtherapeutic anticoagulant response. The results of this trial establish the efficacy of intravenous heparin in the treatment of proximal venous thrombosis and suggest a relation between the effectiveness of heparin and the levels of anticoagulation achieved; such a relation could explain the observed failure of the subcutaneous regimen.     

Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis

BACKGROUND: Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition. METHODS: In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death. RESULTS: Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups. CONCLUSIONS: In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.     

Thromboembolism

The overall incidence of venous thromboembolism is about 0.7 per thousand maternities, but pulmonary embolus is currently the single most common cause of maternal mortality. Major risk factors are operative delivery, age, multiparity and previous thromboembolism. Because of the risks in anticoagulant therapy and the difficulties of clinical diagnosis, it is essential to use objective tests, usually venography for deep-vein thrombosis and lung scan for pulmonary embolus. The acute phase will normally be treated with a continuous infusion of heparin, followed by subcutaneous heparin, given until at least six weeks post-delivery. Warfarin may be substituted after the first week post-delivery. In contrast to the treatment of other forms of thromboembolism, patients with artificial heart valves should be managed with warfarin until 36 weeks of pregnancy. Although the fetal risks in warfarin therapy are greater than those of subcutaneous heparin, the obvious alternative, subcutaneous heparin, does not provide adequate prophylaxis against thromboembolism. In patients who have had venous thromboembolism in the past, the maternal risks do not justify prolonged prophylaxis with subcutaneous heparin as usually given (20 000 units per day) throughout pregnancy. Further clinical trials are necessary to select the best alternatives. Antithrombin III deficiency should be managed with subcutaneous heparin taken from before conception until at least one week post-delivery, when warfarin therapy can be recommended. In addition, the labour should be covered with antithrombin III concentrate.     

Clinical cure of severe, early onset preeclampsia with low molecular weight heparin therapy in primigravida with hyperreactio luteinalis and thrombophilia

Inherited thrombophilias, suggested to be risk factors for ovarian hyperstimulation syndrome and known to be associated with venous thromboembolism during pregnancy, may also increase the risk for preeclampsia (PE). We describe the case of a 29-year-old woman with primary infertility with no history of thrombosis, hypertension or renal disorders. In her first pregnancy, achieved by frozen embryo transfer, she developed severe early-onset (23rd gestational week) PE with heavy proteinuria, and at the same time was found to have enlarged ovaries with hyperreactio luteinalis. After admission we found that she was a heterozygotic carrier of the factor V Leiden mutation. After administering low molecular weight heparin (LMWH) therapy, her blood pressure normalized, proteinuria diminished and her d-dimer values returned to that of a normal pregnant level. The fetus grew normally. Her ovaries normalized during the pregnancy, as determined by ultrasound examinations. At term she delivered spontaneously a normal weight, healthy girl. Previously, only prophylactic LMWH, in subsequent pregnancy, have been administered in patients with thrombophilia and a history of severe PE. We describe a case of spontaneous hyperreactio luteinalis, where the clinical characteristics of PE improved after beginning LMWH therapy in severe, very early onset PE. Inherited thrombophilia, spontaneous hyperreactio luteinalis and PE may be associated phenomena.     

Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis.

BACKGROUND. In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries. METHODS. In a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up. RESULTS. The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to-treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups. CONCLUSIONS. Patients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy.     

Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early onset) or a late pattern (late onset). This observational study was designed to identify whether the onset pattern of OHSS is associated with the occurrence of pregnancy and the early pregnancy outcome. METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized for OHSS after IVF/ICSI treatment and were included in the study. The setting was the Dutch-speaking Brussels Free University Hospital, between June 2000 and September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (P < 0.05). Although in the early group there initially was a 41.5% positive HCG rate per cycle, the clinical pregnancy rate fell to 28.3% as a result of a significantly (P < 0.05) increased preclinical pregnancy loss rate compared with the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple pregnancy rates were high in both groups (40 and 45.5%, respectively), but only in the late group did the incidence reach significance compared with the non-OHSS population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of follicles on the day of HCG were significantly higher in the early OHSS group. However, there was no difference in estradiol values on the day of hospital admittance between the two groups. In addition, the number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS than the estradiol values (87% of the severe cases had > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.     

阿司匹林和利伐沙班预防全膝关节置换后下肢深静脉血栓形成

背景：现中国临床上常用抗凝药物为利伐沙班,但有效预防静脉血栓栓塞性疾病的同时,围手术期出血性并发症发生率也明显增加。有研究表明阿司匹林对深静脉血栓形成和肺栓塞具有良好预防效果,但对于能否将其作为全膝关节置换后预防静脉血栓栓塞性疾病的常规用药至今存在争议。 目的：观察比较阿司匹林和利伐沙班预防全膝关节置换后下肢深静脉血栓形成的疗效和安全性。 方法：初次行单侧全膝关节置换的324例骨关节炎患者随机等分为3组,于置换后12 h,分别用利伐沙班,低分子肝素,阿司匹林干预治疗14 d。所有患者均随访4周。 结果与结论：与低分子肝素组相比,利伐沙班组深静脉血栓发生率降低(P < 0.05),隐性失血量及切口并发症率升高(P < 0.05)。与低分子肝素相比,阿司匹林组深静脉血栓发生率、隐性失血量、切口并发症率、下肢肿胀率和皮下瘀斑率差异均无显著性意义(P > 0.05)。结果证实,利伐沙班拥有较强抗凝效果,但并发症发生率高。阿司匹林与低分子肝素相比疗效和安全性均无差异。阿司匹林作为全膝关节置换后多模式抗凝治疗的一部分,安全有效。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：