Stroke and intracranial venous thrombosis during pregnancy and puerperium

OBJECTIVES: To determine nationally representative estimates of the incidence of stroke and intracranial venous thrombosis during pregnancy and the puerperium, and to identify potential risk factors for these conditions. METHODS: National Hospital Discharge Survey data were analyzed for the period 1979 to 1991. Nationally representative estimates of risk were calculated by age, race, presence of pregnancy-related hypertension, census region, hospital ownership, and number of hospital beds. Multivariate models were developed using logistic regression. RESULTS: There were an estimated 8,918 cases of stroke and 5,723 cases of intracranial venous thrombosis during pregnancy and the puerperium in the United States among 50,264,631 deliveries, giving risks of 17.7 cases of stroke and 11.4 cases of intracranial venous thrombosis per 100,000 deliveries. In the multivariate models, stroke was associated strongly with pregnancy-related hypertension, larger hospital size, and proprietary hospital ownership, and inversely associated with living in the South. Intracranial venous thrombosis was associated with maternal age. CONCLUSIONS: Stroke and intracranial venous thrombosis are relatively common complications of pregnancy and the puerperium. Collectively, rates for these conditions are about 50% greater for the entire period of pregnancy and the puerperium than for the immediate peripartum period.     

Deep-vein thrombosis

Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep-vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D-dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism.     

IL-10 regulates thrombus-induced vein wall inflammation and thrombosis

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.     

The effect of 17 beta-estradiol and endothelin 1 on prostacyclin and thromboxane production in human endothelial cell cultures

The authors present an account on a neonate with dextro-lateral renal venous thrombosis. They focus attention on the diagnostic and therapeutic procedure and compare it with available data from the literature. Contrary to data in the literature, they did not observe in the acute stage of renal venous thrombosis signs of disseminated intravascular coagulation in peripheral blood. It did not prove possible to elucidate the action of any of the factors leading to the development of renal venous thrombosis. After evidence of permanent functional loss of the right kidney nephrectomy was performed. Histopathological examination provided evidence of obliterating thrombosis of the renal veins with partial recanalization and calcifications. The authors emphasize the necessity of early diagnosis of renal venous thrombosis and adequate treatment based on the revealed findings.     

Urokinase protocol for free-flap salvage following prolonged venous thrombosis

The incidence of free-flap failure is reported at 4 to 5 percent. Often, these failures are attributed to postoperative venous thrombosis with salvage rates reported at 42 percent. The use of thrombolytics has been effective in laboratory protocols; however, there have been only case reports to substantiate their use in humans. In this study, we establish a protocol for the administration of urokinase for postoperative venous thrombosis. Upon clinical evidence of venous thrombosis, all patients were urgently returned to the operating room, where the venous anastomosis was resected and a new venous anastomosis was performed. A solution of 250,000 units of urokinase was then infused over 30 minutes through a 25-gauge butterfly inserted into the recipient artery just proximal to the arterial anastomosis. Patients were continued on a daily aspirin (325 mg). More than 600 free flaps have been performed by our group since 1990. In that group of patients, five were diagnosed with postoperative venous thrombosis. Flaps consisted of four radial forearm flaps and one free transverse rectus abdominis muscle flap. All patients were diagnosed late based upon significant changes within the flap. Thromboses were clinically apparent on postoperative days 1 through 6, with an average of 3.6 days. All five patients received urokinase as described. The average age of the patients treated was 43. There were no postoperative hematomas, blood transfusions, or bleeding complications. There were no allergic or anaphylactic reactions to the urokinase. All flaps survived (100 percent) with a mean follow-up of 27 months. The use of urokinase as described in our protocol has been an effective thrombolytic, capable of reversing clinically advanced venous thrombosis when combined with repeated venous anastomosis. We believe this protocol provides a viable option for the treatment of postoperative venous thrombosis.     

The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism

This paper describes the role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Inability to compress the common femoral or popliteal vein is usually diagnostic of a first episode of deep venous thrombosis in symptomatic patients (positive predictive value of about 97%). Full compressibility of both of these sites excludes proximal deep venous thrombosis in symptomatic patients (negative predictive value of about 98%). In patients with suspected deep venous thrombosis or in those who present with suspected pulmonary embolism but have a nondiagnostic lung scan, the subsequent risk for symptomatic venous thromboembolism is very low (<2% during 6 months of follow-up) provided that ultrasonography of the proximal veins remains normal in the course of 1 week (suspected deep venous thrombosis) or 2 weeks (suspected pulmonary embolism). Anticoagulation and further diagnostic testing can usually be safely withheld in these situations. Venous ultrasonography is much less reliable for the diagnosis of asymptomatic, isolated distal, and recurrent deep venous thrombosis than for the diagnosis of a first episode of proximal deep venous thrombosis in symptomatic patients. Clinical evaluation of the probability of deep venous thrombosis or pulmonary embolism, preferably by using a validated clinical model, complements venous ultrasonographic findings and helps to identify patients who would benefit from additional (often invasive) diagnostic testing. Thus, venous ultrasonography is thought to be a very valuable test for the diagnosis and management of patients with suspected deep venous thrombosis or pulmonary embolism.     

Prevention and treatment of adverse effects of corticosteroids in systemic lupus erythematosus

The therapy of deep venous thrombosis consists of several elements and depends on the localization, the age and the extent of the thrombus. This article discusses various types of initial therapy and long-term treatment of venous thromboembolism and also reviews future perspectives of pharmacological treatment. The initial treatment regimens comprise thrombolysis, thrombectomy, inferior vena cava filters and the anticoagulation with either unfractionated heparin or low molecular weight heparins. Various thrombin-inhibitors have been tested for initial treatment of thrombosis, however, further investigations of their efficacy, safety and cost-effectiveness will have to provide firm evidence on their superiority when compared to unfractionated or low molecular weight heparins.     

Risk factors for deep venous thrombosis of the upper extremities

BACKGROUND: Hypercoagulable states and triggering factors (surgery, trauma, immobilization, pregnancy, and use of oral contraceptives) are associated with an increased risk for deep venous thrombosis of the lower extremities. In contrast, risk factors for deep venous thrombosis of the upper extremities have not been identified. OBJECTIVE: To evaluate the prevalence of hypercoagulable states and triggering factors in patients with primary deep venous thrombosis of the upper extremities. DESIGN: Frequency-matched case-control study. SETTING: Hemophilia and thrombosis center at a university hospital. PATIENTS: 36 patients who had primary deep venous thrombosis of the upper extremities, 121 patients who had primary deep venous thrombosis of the lower extremities, and 108 healthy controls. Patients who had deep venous thrombosis of the lower extremities and study controls were frequency-matched by age, sex, geographic origin, and social status with patients who had deep venous thrombosis of the upper extremities. MEASUREMENTS: Resistance to activated protein C was evaluated by a clotting method based on the activated partial thromboplastin time. If test results were abnormal or borderline, DNA analysis for substitution in coagulation factor V gene was done. Antithrombin, protein C, protein S, antiphospholipid antibodies, and total plasma homocysteine levels were also measured. RESULTS: Prevalences of abnormalities of the natural anticoagulant system (9%) and hyperhomocysteinemia (6%) in patients who had deep venous thrombosis of the upper extremities were similar to prevalences of both factors in controls (6% and 7%, respectively) but lower than in patients who had deep venous thrombosis of the lower extremities (31% and 14%, respectively). Antiphospholipid antibodies were found only in patients who had venous thrombosis of the lower extremities (7%). The overall prevalence of hypercoagulable states in patients who had thrombosis of the upper extremities (15%) was similar to that in controls (12%) but was significantly lower than that in patients who had thrombosis of the lower extremities (56%). A recent history of strenuous exercise of muscles in the affected extremity was the most frequent triggering factor for patients who had deep venous thrombosis in the upper extremities (33%). CONCLUSIONS: This preliminary study indicates that the prevalence of hypercoagulable states is low in patients who have primary deep venous thrombosis of the upper extremities.     

New anticoagulant strategies

The limitations of standard heparin have prompted the development of a variety of newer antithrombotic agents. In fact, a LMWH preparation has recently been approved for clinical use in North America. Of these novel preparations, LMWH, the direct thrombin inhibitors, and inhibitors of GPIIb-IIIa have been used clinically and are in advanced stages of evaluation. Not only is LMWH effective in the prevention of venous thromboembolic disease in high-risk patients, but its more predictable dose response makes it an ideal candidate for the treatment of venous thrombosis. Further studies are needed to determine whether LMWH is superior to standard heparin as adjunctive therapy in patients undergoing coronary thrombolysis or angioplasty. Particularly promising in the setting of arterial thrombosis are hirudin, hirulog, and 7E3. With the encouraging results reported to date, it is likely that these agents will soon find their way into the treatment armamentarium of arterial thrombosis.     

A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis

BACKGROUND: Antiphospholipid syndrome (APS) is a disorder of recurrent venous or arterial thrombosis, pregnancy losses, and thrombocytopenia. Recurrent thrombosis has particularly adverse effects on patients prognosis. The factors that influence recurrence and management techniques that prevent these events remain controversial. To add further insight regarding predisposing factors and the prevention of thrombotic recurrence, 61 well-characterized patients with APS were followed up for a median time of 77 months. METHODS: A retrospective cohort study was conducted in which the following factors were examined to determine their influence on thrombotic recurrence: primary vs secondary syndrome; the presence of hypertension, hyperlipidemia, diabetes, or smoking; patient age, sex, and race; pregnancy and oral contraceptives use; and treatment with warfarin sodium, warfarin plus aspirin, aspirin alone, prednisone, or no treatment. RESULTS: There was no difference between patients with primary and secondary APS with respect to recurrent arterial (55% vs 38%, respectively) or recurrent venous (47% vs 50%, respectively) thrombotic events. In all patients with APS, white race (P = .02) was associated with recurrent arterial events. Venous thrombosis occurred during pregnancy or in the postpartum period in 16 (30%) of 53 women and in 8 women taking oral contraceptives. Recurrent arterial and venous thromboses were significantly decreased with prophylactic warfarin use when compared with prednisone use or no treatment. Recurrences were infrequent in patients with prothrombin ratios of 1.5 to 2.0. CONCLUSIONS: Treatment with warfarin was most effective in preventing recurrent arterial and venous thrombosis. Pregnancy and the use of oral contraceptives or prednisone may also influence recurrence.     

Efficacy and safety of low molecular weight heparin in renal transplantation

BACKGROUND: Deep venous thrombosis (DVT) is a common problem with potentially devastating results in patients undergoing major surgical procedures. Certain renal transplant recipients are particularly at risk for allograft loss as a consequence of renal vein and artery thrombosis. Over the past few years, low molecular weight heparin has been well established as an accepted modality of treatment and prophylaxis of DVT. The efficacy and safety of low molecular weight heparin in the prophylaxis of DVT following renal transplantation in adults has not previously been reported. METHODS: Dalteparin was administered to 120 adult renal transplant recipients postoperatively at the Oregon Health Sciences University. RESULTS: No patient developed allograft arterial or venous thrombosis. One patient developed subclavian vein thrombosis. No bleeding complications were encountered, and side effects were very minimal. CONCLUSION: Prophylaxis with dalteparin is an effective and safe modality for the prevention of thrombosis in adult patients undergoing renal transplantation.     

Upper limb thrombosis associated with assisted conception treatment

Three cases of upper limb deep venous thrombosis occurring in association with assisted conception treatment are presented. The accepted argument that lower limb thrombosis occurring in cases of complicated or severe hyperstimulation syndrome represents the likeliest thrombo-embolic disorder in this situation is questioned.     

Cockett syndrome. Initial results with percutaneous treatment in 6 patients

Intimal hypertrophy with venous spur formation caused by compression of the left common iliac vein by the right common iliac artery is advanced as the etiology of the higher incidence of deep venous thrombosis involving the left leg. In most cases of left iliofemoral thrombosis no underlying compression syndrome is detected or treated because the left common iliac vein has to be cleared from thrombi before compression can be identified. A series of 6 consecutive retrospectively analyzed patients with acute left iliofemoral thrombosis is presented. In these patients a left iliac vein compression syndrome was detected after percutaneous intraluminal thrombolysis with Actilyse (rt-PA). This compression was successfully relieved by insertion of a wall stent. Percutaneous treatment of Cockett's syndrome seems an attractive alternative for conservative and/or surgical management.     

Mesenteric venous thrombosis probably due to hereditary thrombophilia in an 18-year-old boy

The authors describe the case-history of an 18-year-old patient with an extensive venous mesenteric thrombosis. The case proved fatal despite repeated surgery as a result of relapsing gangrene of the small intestine with diffuse stercoral peritonitis. Thrombosis of the mesenteric veins is a rare disease and accounts only for 4 to 10% of all acute intestinal episodes. The cause of the disease is either idiopathic but more frequently it is associated with various types of coagulopathy. In this context the authors discuss etiological factors, symptoms, diagnosis as well as possible treatment of acute mesenteric venous thrombosis.     

Thrombosis of tibial arteries in a patient receiving tamoxifen therapy

BACKGROUND: Tamoxifen has been used extensively as adjuvant therapy in the treatment of pre- and post-menopausal patients with breast cancer. One of its known complications is venous thromboembolism. However, arterial thrombosis has been reported rarely. METHODS: A 49-year-old patient with breast cancer had had a total mastectomy 3 years earlier. She was receiving tamoxifen therapy when she developed a sudden onset of pain and numbness of the left foot and calf. An arteriogram showed thrombosis of her tibial arteries. RESULTS: This thrombosis was lysed successfully with urokinase therapy, and tamoxifen therapy was discontinued. At follow-up 4 months later, the patient had normal circulation to both legs. CONCLUSIONS: Patients receiving tamoxifen should be monitored closely for the development of venous or arterial thromboembolism.     

Flow diagram or prose: does the format of practice guidelines matter?

BACKGROUND: Hematopoietic and organ transplantations are increasing worldwide with more patients receiving immunosuppressive therapy. Neurological problems may complicate the posttransplant period. Possible causes include the conditioning regimen (e.g., seizures with busulfan), central nervous system infections (viral, bacterial, and fungal), or factors secondary to the immunosuppressive therapy and side effects of drug treatment (e.g., cyclosporine and tacrolimus). Sinus venous thrombosis, the occlusion of a cerebral venous vessel or a sinus, is an unusual cause of neurologic symptoms in patients after transplantation, and this has not been reported in the literature previously. METHODS: Three patients presenting with various neurological symptoms after allogeneic bone marrow transplantation underwent computed tomography scans and magnetic resonance imaging as a primary diagnostic procedure. RESULTS: In all patients, sinus venous thrombosis was found as the cause for seizures; it was the cause of disturbance of consciousness in two patients and headaches in two patients. All symptoms resolved without any neurologic deficiency after anticoagulation therapy with heparin followed by dicumarol. CONCLUSION: We conclude that sinus venous thrombosis should be considered as a cause of neurological symptoms in patients after transplantation under immunosuppressive therapy. Diagnosis is rapidly confirmed by noninvasive magnetic resonance imaging angiography. Therapeutic heparinization is the treatment of choice.     

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.     

Peptide vaccination with an anchor-replaced CTL epitope protects against human papillomavirus type 16-induced tumors expressing the wild-type epitope

PURPOSE: Upper-extremity thrombosis appears to be more frequent today, comprising about 2% of all deep venous limb thrombosis. Its severity depends on the type of possible complications, i.e., pulmonary embolism and post-thrombotic sequelae. In this retrospective series, we investigated both the predisposing factors and the evolution of upper-extremity deep venous thrombosis. METHODS: Forty-nine consecutive patients (24 men and 25 women, mean age 50.2 years) with upper extremity deep venous thrombosis documented by color Doppler ultrasonography (n = 47) or phlebography (n = 2) were included in the study. RESULTS: Clinical manifestations were mainly pain (81.6%) and edema (93.9%). Mean time between the onset of clinical signs and diagnosis was 7.2 days. Thrombosis involved humeral (26.5%), axillary (46.9%), subclavian (73.5%) and jugular (24.5%) veins. Causative factors were malignancies (32.7%), venous catheters (22.4%), deep venous thrombosis related to effort or thoracic outlet syndrome (22.5%) and thrombophilic states (8.2%). During the 6-month follow-up, six patients developed symptomatic pulmonary embolism (12.2%); one recurrence (2.2%) and 19 post-thrombotic sequelae such as residual edema (36.7%) were also observed. Initial therapy included heparin administration, principally subcutaneous low molecular weight heparins (n = 36/49). CONCLUSION: This series highlights the fact that upper-extremity deep venous thrombosis is mainly secondary to either malignancies or catheterization. Moreover, it confirms that color Doppler ultrasonography may be useful in the diagnosis of the disease and also underlines the high frequency of severe complications, i.e., pulmonary embolism and post-thrombotic sequelae. Finally, this study also demonstrates that low molecular weight heparins should be considered as the initial treatment of choice.     

Epidemiological study of angioedema and ACE inhibitors

A total 30,040 pregnancies were reviewed at one institution over 5 years to determine the incidence of venous thrombotic complications. Thirty-one patients experienced such complications related to pregnancy (incidence 0.1%); 13 had deep venous thrombosis and 14 had superficial venous thrombophlebitis diagnosed by duplex ultrasound. Four had pelvic vein thrombophlebitis diagnosed by computed tomography scan; three patients (one from each group) sustained a non-fatal pulmonary embolus. Of those with deep venous thrombosis, 10 (77%) were left-sided, and three (23%) were right-sided. Three had a prior history of deep venous thrombosis and one of pulmonary embolism. Of those with superficial venous thrombophlebitis, seven (50%) were left-sided, six (43%) were right-sided, and one (7%) was bilateral. Most with deep venous thrombosis presented later in pregnancy; three in the first trimester, two in the second, three in the third, and five early postpartum. Most (10/14) with superficial venous thrombophlebitis presented within 48 hours of delivery. Distribution of thrombi in those with deep venous thrombosis was compared with 643 non-pregnant women with a similar condition. A pattern of proximal involvement on the left was found, with left common femoral vein (54% versus 28%, P = 0.03) and superficial femoral vein (62% versus 26%, P = 0.006) more often involved in pregnant patients. The average number of vein segments involved was greater on the left than the right (5.3 versus 3.7). Symptoms of chronic venous insufficiency developed in three with deep venous thrombosis (25%) and in three with superficial venous thrombophlebitis (27%). None had recurrence of deep venous thrombosis. It is concluded that venous thrombotic complications associated with pregnancy are not necessarily benign, with the risk of pulmonary embolism and chronic venous insufficiency not limited to patients with deep venous thrombosis only.     

Neonatal mortality amongst Scottish preterm singleton births (1985-1994)

BACKGROUND: Few studies have compared the incidence of deep venous thrombosis among ethnic groups. OBJECTIVE: To determine the incidence of deep venous thrombosis among ethnic groups. Design: Analysis of the linked California Patient Discharge Data Set from 1991 to 1994. Setting: California. PATIENTS: 17991 patients with idiopathic deep venous thrombosis (thrombosis without cancer or hospitalization within preceding 6 months) and 5573 patients with secondary thromboembolism (thromboembolism occurring within 3 months of seven different events). MEASUREMENTS: Ethnicity was determined by using race as documented in the data set. For idiopathic deep venous thrombosis, standardized age- and sex-adjusted incidences were calculated. For secondary thromboembolism, proportional hazards modeling was done. RESULTS: The annual incidence of idiopathic deep venous thrombosis per 1000000 persons older than 18 years of age was 230 for white persons, 293 for African Americans (rate ratio, 1.27 [95% CI, 1.07 to 1.51]), 139 for Hispanic persons (rate ratio, 0.60 [CI, 0.54 to 0.67]), and 60 for Asians and Pacific Islanders (rate ratio, 0.26 [CI, 0.22 to 0.30]). Compared with white persons, Asians and Pacific Islanders who developed secondary thromboembolism had a significantly lower relative risk (range, 0.22 to 0.61) for all seven conditions analyzed. CONCLUSIONS: Compared with white persons, Asians and Pacific Islanders have a very low incidence of idiopathic deep venous thrombosis and a very low relative risk for secondary venous thromboembolism.