Confusion in the nomenclature of vascular malformations has been a major obstacle to the understanding of these conditions, so that misdiagnosis and treatment inconsistencies are common. Coagulation abnormalities occurring in combination with venous malformations (VM) have been misdiagnosed as Kasabach-Merritt syndrome (KMS), despite marked differences in clinical features, pathology and treatment. A homogenous group of 24 patients with diffuse limb VM was entered into a retrospective chart review study. The VM affected an upper limb in 12 patients, a lower limb in 10 and both in two. Localized intravascular coagulation (LIC) was characterized by a decrease in fibrinogen (0.5-1 g/l), an increase in d-dimers (2-64 micro g/ml) and presence of soluble complex of fibrin (+ to +++). Platelet counts were normal or slightly decreased. Higher VM severity scores were associated with more severe LIC. A number of events such as sclerotherapy, surgery, bone fracture, prolonged immobilization and pregnancy or menstruation triggered conversion of the LIC to disseminated intravascular coagulation (DIC), with bleeding related to factor consumption and multiorgan failure related to disseminated microvascular thrombosis. Clinical symptoms associated with worsening of LIC were pain, thrombosis and bleeding at wound sites or during surgery. None of the patients had the large ecchymotic and inflammatory tumours seen in KMS. Graded permanent elastic compression with heparin therapy was the only effective treatment. In conclusion, VM-associated LIC is a distinctive lifelong coagulopathy that must be differentiated from KMS, which is characterized by platelet trapping within a vascular tumour of infancy. The treatment of the two conditions is very different.

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Bovine and human K-caseinoglycopeptides, two antithrombotic peptides derived from the corresponding K-caseins, were detected in physiologically active concentrations in the plasma of 5-d-old newborn infants after ingestion of cow's-milk-based formula or human milk respectively. It is suggested that these two bioactive peptides are released from milk proteins during digestion.

AimTo quantify the effect of paracetamol on the anticoagulant effect of war farin under normal clinical conditions. Patients and methodsIn a prospective double-blind, cross-over, placebo-controlled study, 11 patients on stable warfarin therapy received in random order two 14-day regimens of paracetamol 4 g day − 1 or placebo, with a 14-day or more wash-out period in between, time necessary to fulfil the inclusion criteria. ResultsIn patients on paracetamol, the mean maximum increase in the International Normalized Ratio (INR) observed was 1.04 ± 0.55 vs. 0.20 ± 0.32 in those on placebo ( P = 0.003). The mean maximum INR observed was significantly higher with paracetamol than with placebo (3.47 vs. 2.61, P = 0.01). In patients receiving paracetamol, the mean observed INR was significantly increased after 4 days ( + 0.6 ± 0.6, P < 0.001). ConclusionParacetamol at 4 g day − 1 induces a significant increase in INR in patients receiving a stable regimen of warfarin, increasing the risk of bleeding associated with warfarin.

In patients with an implanted external ventricular assist device, the platelet activation profile displays a persistent activation with a preserved reactivity associated with a persistent high inflammatory state and endothelial activation.

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Among inherited risk factors for venous thrombosis, the most common are the FV-G1691A and FII-G20210A polymorphisms. The FV-G1691A polymorphism is preferentially observed in Europe, with differences between European countries. The FII-G20210A polymorphism is observed all over the world. The study was designed to compare the prevalence of the FV-G1691A and FII-G20210A polymorphisms in a large French population of unrelated individuals with no thrombotic disease history and to determine the age and geographical distributions. Over a period of 18 months, 6154 individuals were included throughout France and FV-G1691A and FII-G20210A polymorphisms were determined. The FV-G1691A prevalence was 3.84% (95% confidence interval 3.35-4.33) and the FII-G20210A prevalence was 3.07% (95% CI 2.63-3.51). A north-east/south-west gradient was observed in the FV-G1691A geographical distribution. No difference was observed in the geographical distribution of FII-G20210A polymorphism nor in the age distribution of the two polymorphisms. The prevalence of the two polymorphisms was similar whatever the blood group (O or non-O). Plasma D-dimers were significantly higher in healthy individuals with FV-G1691A but not in individuals with FII-G20210A. Thirty percent of variation in plasma prothrombin level was explained by environmental factors (serum cholesterol, age, oral contraception, hormonal replacement therapy, body mass index, sex) and genetic factors (FII-G20210A). As expected, individuals with FII-G20210A displayed higher plasma prothrombin level compared with individuals with wild type. However, this was not associated with a modification of the fibrin clot elastic modulus. This study shows a differential distribution of the two polymorphisms among the French territory. These polymorphisms confer a very mild hypercoagulable state as shown by the limited increased in basal D-dimers in mutated FV-G1691A populations and only a trend that does not reach statistical significance for FII-G20210A population.

KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested in vitro on human platelet function, and its effects were compared to those of RGDS, a tetrapeptide from human fibrinogen. Both peptides had a high probability of initiating a p-turn and were highly hydrophilic. KRDS inhibited ADP-induced platelet aggregation [median inhibitory concentration (1C5,J 350 pM] and fibrinogen binding 360 pM) to a lesser extent than RGDS (IC50 75 pM and 20 pM, respectively). Different from RGDS, thrombin-induced serotonin release was inhibited by KRDS (750 pM) on normal platelets (55 loo/,) and type I Glanzmann's thrombasthenia platelets (43% f 1). However, KRDS had no effect on cytoplasmic Ca2 + mobilization, inositol phospholipid metabolism or protein phosphorylation (myosin light chain P20 and P43). In contrast to RGDS, KRDS does not inhibit the binding of monoclonal antibody PAC-1 to activated platelets. KRDS and RGDS inhibited 4P-phorbol-12-myristate-13-acetate (PMA)-induced aggregation and fibrinogen binding, while proteins were normally phosphorylated. Thus, the tetrapeptide KRDS is (a) an inhibitor of serotonin release by a mechanism independent of protein phosphorylation and (b) an inhibitor of fibrinogen binding and, hence, aggregation by a mechanism that may not necessarily involve its direct binding to the glycoprotein IIb-IIIa-complex.It is well established [l, 21 that fibrinogen interaction with platelets is essential for platelet aggregation and that fibrinogen binds to a specific receptor on the platelet surface: the glycoprotein IIb-IIIa complex (GPIIb-IIIa). Unstimulated platelets do not bind fibrinogen. In type I Glanzmann's thrombasthenia, characterized by the absence of platelet membrane GPIIb-IIIa, fibrinogen binding and ADP-or thrombininduced platelet aggregation are not observed. Yet the mechanisms of fibrinogen receptor exposure on the platelet surface and of fibrinogen interaction with GPIIb-IITa are not completely understood. Two binding sites have been identified on the fibrinogen molecule: a decapeptide in the carboxy-terminal region of the y-chain (LGGAKQAGDV; residues 402 -41 1) and a tetrapeptide in the carboxy-terminal region of the a-chain (RGDS; residues 572-575). Both peptides inhibit aggregation and fibrinogen binding to ADP-activated platelets [3]. Recently it has been shown that RGDS becomes more chemically cross-linked to residues 109-171 of GPIIIa number of similarities have been previously reported between these two clotting processes [6, 71. Moreover, structural homology has been found between cow K-casein and human fibrinogen y-chain [8]. Recently, Jolles et al. [9] showed that both the natural and the corresponding synthetic undecapeptide MAIPPKKNQDK of cow K-casein (residues 106-116) were more inhibitory of ADP-induced platelet aggregation and fibrinogen binding than the C-terminal dodecapeptide, HHLGGAKQAGDV, of the human fibrinogen y-chain (residues 400-411). Based on these observations, we looked for a peptide from a milk protein that is structurally and fun...