Management of patients on long-term oral anticoagulant therapy undergoing elective surgery: survey of the clinical practice in the Italian anticoagulation clinics.

In the perioperative management of patients on long-term oral anticoagulant (OAC) therapy the problem is balancing the thromboembolic (TER) and the haemorrhagic risk (HR) in the perioperative period. The Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA) activated an online registry from November 2001 to August 2003 in order to collect information on the management of these patients in Italy. Four hundred and eleven patients, undergoing elective major (18%) and minor surgery (82%), from 7 centres, were registered. Three hundred and ninety-nine out of 411 patients received LMWH either once a day (310 patients) or twice a day (89 patients) during OAC therapy discontinuation. Two thromboembolic (0.48%) and 16 bleeding events (7 major; 1.7%) were reported. Notwithstanding the lower doses of heparin (54.3 U/kg o.d. and 64.4 U/kg b.i.d.), the thromboembolic complications are in line with those reported in the literature. The data of this study suggest that the intervention with LMWH may be relevant only in the high-risk patients as already proposed by others.

Critical bleeding in pregnancy: a novel therapeutic approach to bleeding.

AIM: In the developed countries the frequency of life threatening post-partum hemorrhages (PPH) is 1 in 1,000 deliveries with a risk of death of 1-2/100,000 deliveries. Hysterectomies for intractable bleeding are carried out in approximately 50% of the cases. The majority of PPH have obstetrical causes, most frequently atony of the uterus. Hereditary and acquired hemostatic defects are very rare. Guidelines of standard surgical and medical measures are available. In this paper we focus on the use of activated recombinant factor VII (rFVIIa) in PPH. METHODS: A computerized literature search was carried out in PubMed and Ovid for papers published between 2001 and 2005 in the English literature reporting on life-threatening PPH treated with rFVIIa after failure of conventional therapy, including hysterectomy. RESULTS: We identified 11 papers including 39 patients; in 18 of them the laboratory data were indicative for disseminated intravascular coagulation and in 24 hysterectomy was carried out. Controlled or reduced bleeding was reported in 38 out of 39 treated patients. CONCLUSIONS: The bleeding can occur in a series of events conductive to metabolic complications, hypoxia, disseminate intravascular coagulation, organ damage and multiorgan failure, progressively exhaustive. The therapeutic intervention must be instituted as early as possible before successive complications ensue. These preliminary reports in PPH after failure of conventional standard therapy suggest that rFVIIa is an active agent but should be administered as early as possible before the consequences of severe and intractable bleeding.

von Willebrand factor ristocetin cofactor (VWF:RCo) assay: implementation on an automated coagulometer (ACL).

BACKGROUND: VWF:RCo assay is the standard and widely used laboratory test for von Willebrand disease (VWD) diagnosis. It is hampered by high intra- and inter-assay imprecision and is time consuming. Automation may improve the assay performance and allow its routine application. OBJECTIVE: Automation of VWF:RCo on the ACL 7000 coagulometer (Instrumentation Laboratory, Milan, Italy) and its evaluation in VWD diagnosis. METHODS AND MATERIALS: Method performance determination: precision, detection limit (DL), interferences, dose-response curve. Method comparison: analysis of 105 plasma samples from normal subjects (50), VWD type 1 (24), VWD type 2 (24) and VWD type 3 (7) with ACL VWF:RCo and comparison with the reference aggregometric (AGM) method. RESULTS: ACL VWF:RCo: CVs around 10% vs. 19% of AGM method; DL: 0.08 U mL(-1); potential interferences from bilirubin, triglycerides and hemoglobin, avoided by suitable plasma dilution; high correlation with AGM VWF:RCo (Deming regression Y =-0.0277 + 1.0519X) either in normal or VWD plasmas. In VWD types 1 and 2, the VWF:RCo/VWF:Ag ratios are >0.6 or <0.6, respectively, when calculated with both AGM and ACL VWF:RCo values. CONCLUSIONS: The automated VWF:RCo on the ACL 7000 coagulometer shows precision improvement and high correlation with the reference AGM method. The test allows the diagnosis of both quantitative (VWD types 1 and 3) and qualitative (VWD type 2) forms of the disease. These results and the assay feasibility make it a suitable and reliable test for the routine diagnosis of VWD.

Long-term evaluation of a novel surgical approach to the pseudotumour of the ilium in haemophilia: exeresis and transposition of the omentum in the residual cavity.

Pseudotumour of the ilium is a rare but severe complication in haemophiliacs. Excision is often complicated by infections, fistulation and extensive pelvic bone destruction. In 1978, the first author carried out excision of the pseudotumour with transposition of the omentum in the dead cavity to avoid recurrence. This type of surgery has been carried out in three additional patients. The long follow-up of these four patients suggests that this procedure is feasible and curative; local bleeding, infection and fistulation did not recur and the patients remained ambulant with the aid of appropriate devices.

The continuous infusion of recombinant activated factor VIIa (rFVIIa) in patients with factor VIII inhibitors activates the coagulation and fibrinolytic systems without clinical complications.

The standard modality of administration of rFVIIa to patients with FVIII and FIX inhibitors is the intermittent infusion every 2 to 6 hours. No untoward local or systemic effects have been reported; laboratory data of activation of coagulation were reported in the presence of coexistent problems (sepsis, septic shock) or with high doses. We treated four patients with FVIII inhibitor with rFVIIa administered by continuous infusion by a central vein catheter, monitoring the signs of systemic activation of the hemostatic system. The F(1+2) prothrombin fragments and the D-dimer increased after the bolus, and remained above the baseline values throughout the treatment period. These variations observed during the infusion period were not accompanied by clinical events.

L-asparaginase in acute lymphoblastic leukemia treatment: the role of human antithrombin III concentrates in regulating the prothrombotic state induced by therapy.

It is well known that L-asparaginase (L-Ase) treatment may cause thrombotic events in patients with acute lymphoblastic leukemia (ALL). The mechanism of this effect is not well understood although a reduction in plasma antithrombin III (AT III) levels is observed. In our study, a group of patients treated with L-Ase received AT III concentrates as adjuvant treatment. This adjuvant treatment reduced the levels of plasma D-dimer and thrombin-antithrombin complex, which are considered as early markers of a hypercoagulability state. These preliminary data suggest that large randomized trials will have to be conducted to improve our understanding of the role of AT III concentrates in ALL therapy.