Portal vein thrombosis in liver cirrhosis: incidence, management, and outcome.

BACKGROUND: Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients. METHODS: The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy. RESULTS: Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053). CONCLUSION: We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.

[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view]. / Die heparininduzierte Thrombozytopenie (HIT II) : Eine medizinökonomische Betrachtung.

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to be determined. The objective is to describe the clinical course and treatment plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a past history of end stage renal disease (ESRD) of unknown etiology was initiated on NHD in February 2005. His clinical and biochemical parameters improved after conversion to NHD. However, excessive bleeding at the vascular access sites complicated his treatments. Clinical investigations revealed development of HIT Alternative therapeutic strategies were attempted to enable our patient to continue NHD: unfractionated heparin, citrated regional anticoagulation, Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific clinical challenge. We speculate that the augmented exposure of heparin coupled with a primed autoimmune response may be responsible for the development of HIT in our patient. Further research is required to elucidate the appropriate clinical monitoring and treatment strategy for this patient.

Dermatan sulfate versus unfractionated heparin for the prevention of venous thromboembolism in patients undergoing surgery for cancer. A cost-effectiveness analysis.

BACKGROUND: In a recent clinical trial, dermatan sulfate was found to be more effective than unfractionated heparin (UFH), but equally well tolerated, for the prevention of deep vein thrombosis (DVT) after major surgery for cancer. OBJECTIVE: To perform a cost-effectiveness analysis of dermatan sulfate versus UFH in this clinical setting. DESIGN AND SETTING: This was a retrospective economic analysis using data from a randomised clinical trial, and was performed from the hospital perspective. METHODS: Clinical event rates were extrapolated from the observed venographic DVT rates, using appropriate assumptions from the scientific literature. The economic effects of switching DVT prophylaxis from UFH to dermatan sulfate and the potential lives saved were assessed by a predictive decision model. RESULTS: The per patient cost, including the burden of residual thromboembolic events and major bleeding complications, was estimated to be 154 euros (EUR) for dermatan sulfate and EUR185 for UFH (1998 values). With reference to a potential target population of 60,000 patients/year undergoing surgery for cancer in Italy, the total prophylaxis-associated cost was EUR9,258,000 for dermatan sulfate and EUR11,096,000 for UFH, whereas the potential deaths from prophylaxis failure were 204 and 392, respectively. This represented a saving of EUR1,838,000 and 188 potential lives per year with the dermatan sulfate option. The final costs and effects were mainly sensitive to variations in the rates of DVT and pulmonary embolism, and to the possible need for 1 extra day of hospitalisation because of the earlier preoperative initiation of dermatan sulfate prophylaxis. CONCLUSION: Dermatan sulfate is more cost effective than UFH for the prevention of postoperative venous thromboembolism in patients with cancer. If the hospital stay needs to be prolonged, then the dermatan sulfate option may involve a small additional cost (EUR47) per potential life saved.

Danaparoid sodium.

Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT). It has excellent bioavailability following s.c. injection. Danaparoid has little effect on routine coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be monitored carefully. For its FDA approved indication (DVT prophylaxis during hip replacement surgery), its cost per day is approximately eight times more than LMWH. Even though monitoring is not routinely necessary according to the manufacturer for its approved indication, monitoring is frequently necessary when it is used in other clinical scenarios. Its higher cost than comparable therapies for DVT prophylaxis and the low availability of the FXa assay in most non-tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid has been found to be effective in the treatment of HIT although this is an off label use, despite being the most frequent reason why danaparoid is used.

Cost effectiveness of danaparoid compared with enoxaparin as deep vein thrombosis prophylaxis after hip replacement surgery.

Guidelines for prophylaxis of deep vein thrombosis (DVT) after hip replacement surgery suggest the use of twice-daily low-molecular-weight heparin as one treatment option. Danaparoid, a low-molecular-weight heparinoid, and once-daily enoxaparin are recently released dosage forms that have been evaluated as pharmacoprophylaxis for DVT after hip replacement surgery. Incremental cost-effectiveness ratio calculations using published efficacy and safety data suggest that enoxaparin (40 mg) daily is the more cost effective of these two agents as routine prophylaxis after hip replacement surgery.

[Thrombocytopenia due to heparin therapy. Use of danaparoid (Orgaran), 13 monocentric cases under authorization of temporary prescription (ATU)]. / Thrombopenies sous héparinothérapie. Utilisation du danaparoïde (Orgaran), trieze cas monocentriques sous le régime de l'ATU.

Since September 1994, danaparoid (Orgaran), a heparinoid, has been used in our centre to treat patients with thrombocytopenia occurring during heparin therapy and who need continuing antithrombotic therapy. We carried out a retrospective study using clinical and biological data on the first 13 consecutive patients treated with danaparoid (for 1 to 18 consecutive days). The platelet count returned to normal for ten patients, but one patient died having contracted a severe sepsis and bleeding occurred in one patient with acute renal failure. In the three other cases, the diagnosis of heparin induced thrombocytopenia (HIT) was in retrospect unlikely and the death of these patients was related to severe underlying diseases which were held responsible for thrombocytopenia. We confirm that danaparoid appears to be an effective, well-tolerated substitute for heparin in HIT patients. The French regulation Temporary Authorization for Prescribing Medicines allowed the prompt use of this as yet unmarketed drug and collection of reliable and pertinent data.