Hypogonadotropic Hypogonadism Associated with Hereditary Hemorrhagic Telengiectasia

A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis.

Inferior vena cava filters in the management of cancer-associated venous thromboembolism: a systematic review

This study systematically reviews outcomes after inferior vena cava (IVC) filtration in cancer-associated venous thromboembolism (VTE). A comprehensive review of the English language literature was performed using MEDLINE, COCHRANE library, Embase and CINAHL on outcomes (i.e., pulmonary embolism, recurrent DVT, postphlebitic syndrome and survival) following IVC filtration in cancer-associated VTE. Fourteen studies with 2,154 cancer patients receiving IVC filters post-VTE were included. All were observational studies. The mean duration of followup was 0.7–38 months and mean patient age was 56.8– 68 years. Among study participants, 47–87% had stage 3 or 4 cancers. Of the 47–93% of filters inserted for contraindications to anticoagulation (AC), 10–33% were placed for relative contraindications. Recurrent PE was seen in 0–6%, fatal PE in 0–4.5%, recurrent DVT in 0–18.2%, postphlebitic syndrome (PPS) in 0–2.7%, and IVC thrombosis (ICVT) in 3% of cancer patients. Median survival post-filter insertion was 2–10 months. Evidence supporting the utility of IVC filter insertion in cancer-associated VTE is limited to observational studies only. Preliminary data demonstrate similar safety and efficacy of filters in cancer and noncancer populations. The combination of filters and anticoagulation is no more effective than either modality alone. Retrievable filters are an attractive option for prevention of VTE in the presence of temporary risk factors or temporary contraindications to anticoagulation in patients who have a reasonable life expectancy, but there is no evidence to support their preferential use in patients with advanced malignancy.

Treatment of Symptomatic Lower Extremity Acute Deep Venous Thrombosis: Role of Mechanical Thrombectomy

Systemic anticoagulation with heparin or its unfractionated derivatives followed by warfarin therapy has been the mainstay of treatment in patients with lower extremity deep venous thrombosis (DVT). Although heparin is an effective treatment modality in preventing thrombus propagation, it provides minimal therapeutic effect in dissolving preexisting venous thrombus. The clinical consequence of DVT, owing in part to loss of venous endothelial and valvular function, is postphlebitic syndrome or chronic venous insufficiency. Current advances in endovascular therapy have resulted in various endovascular thrombectomy systems that can effectively remove a large venous thrombus burden, which may represent a potential advantage of preserving venous valvular function and thereby reduce the likelihood of postphlebitic syndrome. In this article, we review a variety of surgical and interventional methods in venous thrombus removal. Current treatment modalities using mechanical thrombectomy devices and pharmacomechancial thrombectomy strategy are also discussed.

The Risk of Venous Thromboembolism Following Hospitalization in Medical Patients without Cancer.

Background: Heparin therapy is recommended for prevention of venous thromboembolism (VTE) in hospitalized medical patients. This recommendation is based on studies demonstrating the efficacy of heparin in preventing surrogate endpoints such as positive venograms or vascular ultrasounds in patients without symptoms or signs of VTE. The efficacy of low-dose heparin prophylaxis in preventing clinical VTE in hospitalized general medical patients remains uncertain. Short-term studies suggest that up to 15% of such patients experience subclinical thrombosis during or shortly after hospital admission. Objective: To quantify the incidence of clinically significant events, we determined the rate of readmission for acute venous thromboembolism (VTE) in patients without cancer discharged from an medical inpatient stay. Methods: The study was performed using nation-wide DVA administrative and inpatient pharmacy databases. The source population was all male patients without a diagnosis of cancer admitted to any DVA medical service between April 1, 2002 and September 30, 2005. To qualify, the index medical admission (IMA) had to be longer than 3 days and not preceded by a surgical admission. Using ICD-9 codes for VTE and postphlebitic syndrome, subjects were categorized as follows: no history of VTE (noVTE), a history of prior VTE (pVTE) and an IMA of acute VTE (aVTE). Annualized rates of subsequent readmission for VTE were determined in each of these groups by life-table analysis and Cox proportional hazard models were used to derive hazard ratios (HR). Results: The final cohort consisted of 206,290 subjects of whom 0.36% had a subsequent readmission for VTE. The rates of VTE in the first year following IMA were 7.15%, 2.13% and 0.30% for aVTE, pVTE and noVTE groups respectively. Age adjusted Cox proportional models demonstrated a HR of 24.3 (95%CI 20.6, 28.8) for the aVTE and 7.7 (95%CI 5.9, 10.0) for the pVTE compared to the noVTE group. In the noVTE group, 25% of patients received warfarin or therapeutic heparin, 11% received only heparin prophylaxis and 64% received no anticoagulant therapy at any time during the IMA, with readmission for VTE occurred in 0.3%, 0.2% and 0.2% of patients in these subgroups respectively. Conclusions: Despite high rates of sub-clinical VTE in clinical trials enrolling patients admitted to medical services, we found that only 0.36% of patients are readmitted to hospital for VTE following discharge. An exception appears to be patients with a history of VTE who have considerably higher rates (2.13%). The rate of readmission for VTE in patients with an index admission for VTE (7.15%) is within the expected range, and consistent with other published reports. Despite the low utilization rates of heparin prophylaxis in patients without prior VTE, readmission with clinically apparent VTE is distinctly uncommon. These results support the argument claiming that prophylaxis may be unnecessary in the majority of medical patients without known malignancy or prior VTE.

Venous Thromboembolism Treatment

The potential morbidity and mortality associated with venous thromboembolism (VTE) dictates rapid diagnosis and effective treatment. An understanding of basic anatomy permits a strategic approach to diagnosis and decisions regarding initial therapy. VTE can include the superficial or deep venous systems of the lower (most common) and upper extremities. Because deep vein thrombosis (DVT) of the proximal vessels (iliac, femoral veins) is associated with the greatest risk of pulmonary embolism (PE) (as well as chronic complications such as postphlebitic [thrombotic] syndrome), a proactive response, which may include anticoagulant therapy pending a definitive diagnosis, is recommended. Many DVTs begin in the calf veins and most, in all likelihood, resolve spontaneously. The probability of extension to the popliteal vein or above (where embolism is more likely) is determined by the prothrombotic environment. Proximal thrombi resolve slowly with anticoagulant therapy, and may be detectable in up to 50% of patients 1 year later. Approximately 10% of patients develop postphlebitic syndrome within 5 years—a complication from progressive valvular damage that increases in prevalence with recurrent events (Anderson et al., 1991). Approximately 10% of all PEs are rapidly fatal, and an additional 5% of patients die even after treatment is initiated. Up to 5% of patients develop pulmonary hypertension because of limited thrombus resolution (Kearon, 2003). The diagnosis of DVT and PE is difficult and requires a mixture of clinical suspicion and objective testing. A complete history with attention to specific symptoms and signs should be recorded; a thorough family history is also invaluable. The laboratory evaluation is critical in establishing an unequivocal diagnosis, but most of the tests currently used are not of uniform high sensitivity and specificity. Thus, an accurate diagnosis requires experience and attention to detail. The cardinal symptoms of DVT are pain and swelling in the lower extremity. The pain may be sharp and sudden in onset or come on more gradually and be reported as restricting in character. There may be little or no swelling, or the entire lower extremity may be markedly enlarged. On examination, there is frequently reddish-purple discoloration of the leg in comparison with the noninvolved side.

Incidence, Risk Factors, and Outcomes of Catheter-Related Thrombosis in Adult Patients With Cancer

Purpose Thrombosis of long-term central venous catheters (CVC) is a serious complication that causes morbidity and interrupts the infusion of chemotherapy, intravenous medication, and blood products. We performed a prospective study to examine the incidence, risk factors, and long-term complications of symptomatic catheter-related thrombosis (CRT) in adults with cancer. Patients and Methods Consecutive patients with cancer, undergoing insertion of a CVC, were enrolled and prospectively followed while their catheter remained in place plus 4 subsequent weeks or a maximum of 52 weeks, whichever came first. Patients with symptomatic CRT were followed for an additional 52 weeks from the date of CRT diagnosis. The end points were symptomatic CRT, symptomatic pulmonary embolism (PE), postphlebitic syndrome, and catheter life span. Results Over 76,713 patient-days of follow-up, 19 of 444 patients (4.3%) had symptomatic CRT in 19 of 500 catheters (0.3 per 1,000 catheter-days). The median time to CRT was 30 days and the median catheter life span was 88 days. Significant baseline risk factors for CRT were: more than one insertion attempt (odds ratio [OR] = 5.5; 95% CI, 1.2 to 24.6; P = .03); ovarian cancer (OR = 4.8; 95% CI, 1.5 to 15.1; P = .01); and previous CVC insertion (OR = 3.8; 95% CI, 1.4 to 10.4; P = .01). Nine of the 19 CRT patients were treated with anticoagulants alone, eight patients were treated with anticoagulants and catheter removal, while two patients did not receive anticoagulation. None had recurrent CRT or symptomatic PE. Postphlebitic symptoms were infrequent. Conclusion In adults with cancer, the incidence of symptomatic CRT is low and long-term complications are uncommon.

Emerging anticoagulants for the treatment of venous thromboembolism

SummaryAnticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists,such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

Endoluminal Recanalization in a Patient with Phlegmasia Cerulea Dolens Using a Multimodality Approach

Phlegmasia cerulea dolens, a rare complication of deep venous thrombosis, has traditionally been difficult to treat. The patient described in this report posed additional therapeutic challenges based on a history of heparin-induced thrombocytopenia. She presented with severe leg pain and swelling, and a venogram showed occlusion of both her inferior vena cava and right iliac vein. The use of a multimodality approach, both chemical and mechanical, was successful in removing the venous occlusion, thereby preventing further complications, such as circulatory shock, postphlebitic syndrome, and venous gangrene.