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Background and Objective: The bleeding manifestations frequently observed in patients with immunoglobulin light chain amyloidosis (AL) have been attributed to different pathogenetic factors: amyloid deposits in several organs and systems leading to failures of these latter, the affinity of amyloid for some clotting factors, and the presence of plasma components interfering with fibrin formation could all induce alterations of clotting tests. This investigation was aimed at defining the prevalence of clotting abnormalities and their clinical manifestations in patients with AL., Design and Methods: Thirty-six consecutive patients with biopsy proven amyloidosis and documented monoclonal gammapathy were enrolled within one year. The following clotting tests were considered in the study: activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), Russell's viper venom time (RVTT), fibrinogen, factor X and alpha-2 antiplasmin., Results: Hemorrhagic manifestations were mild to moderate in nine patients, but severe and untractable in one. The most frequent clotting anomaly was defective fibrinogen conversion to fibrin, as demonstrated by prolongation of both TT (85% of cases) and RT (90% of cases). Low levels of factor X activity were observed in about 1 out of 4 samples, while fibrinogen and alpha2 antiplasmin levels were distributed over a wide range of values. PT was prolonged in 8 and aPTT in 25 patients. The search for lupus anticoagulant was negative in samples showing a prolongation of aPTT and/or RVVT., Interpretation and Conclusions: The prolongation of TT and RT is not dependent on either the presence of a heparin-like substance in the plasma or on fibrinogen levels; furthermore, the prolongation of RVVT is not related to factor X level. The hypothesized presence in the plasma of an inhibitor of fibrin formation could also affect factor X activation by Russell viper venom. The prolongation of TT and RT represents a peculiar feature of amyloidosis. The variability in the behavior of the other clotting times and hemostatic factors studied is mirrored in the heterogeneity of the clinical features observed in this disease.

Background and Objective: Desmopressin (DDAVP) may shorten bleeding time in patients with disorders of platelet function, but its mechanism of action in these conditions is still a matter of debate. In particular, contrasting results have been obtained concerning the ability of DDAVP to interact with platelets and to activate them directly. To gain further information on the DDAVP-platelet interaction, we studied the in vitro and ex vivo effects of DDAVP on platelet function., Design and Methods: Platelet responses to DDAVP both as a single agent and in conjunction with agonists of platelet activation were investigated. For in vitro experiments platelets were obtained from healthy adult volunteers, while the ex vivo effects of DDAVP were studied in 12 patients with a bleeding disorder receiving a test dose of this drug., Results: DDAVP in vitro did not induce either platelet aggregation or surface expression of the activation-dependent antigens; it did, however, greatly inhibit platelet aggregation response to vasopressin (AVP) and increased the maximal extent of platelet aggregation induced by collagen and ADP. DDAVP infusion did not promote the expression of activation antigens, but significantly enhanced ex vivo platelet aggregation stimulated by ADP and collagen. This priming effect was observed in patients with von Willebrand's disease, hemophilia A, May-Hegglin anomaly, gray platelet syndrome and Ehlers-Danlos syndrome. In all these patients bleeding time was shortened by DDAVP infusion. In contrast, neither platelet aggregation nor bleeding time was modified in two subjects with Glanzmann's thrombasthenia., Interpretation and Conclusions: Our in vitro experiments indicate that DDAVP interacts directly with platelets and facilitates their activation via other agonists. In vivo results suggest that this effect occurs and is clinically relevant in patients with platelet dysfunction responding to DDAVP with a shortening of bleeding time.

Background and Objective: It has been previously suggested that activation of coagulation and fibrinolysis may sometime occur in patients with unruptured aortic aneurysm. However, the incidence of this complication and the effect of surgical repair are unknown. The objective of our study was to gain further information on this topic., Methods: We investigated activation of the hemostatic process in 20 consecutive patients with unruptured abdominal aortic aneurysm. We then evaluated the effect of surgical repair of the vascular abnormalities., Results: Both before and in the first week after surgery, the large majority of patients showed clear signs of activation of coagulation (increased plasma levels of prothrombin fragment 1 + 2 and fibrin peptide A), and many had low levels of the natural anticoagulant antithrombin III. Platelets were activated in all cases (high levels of plasma beta-thromboglobulin), and signs of platelet consumption (thrombocytopenia and/or increased mean platelet volume) were present in most of them., Interpretation and Conclusions: Activation of the hemostatic process occurs in nearly all patients with abdominal aortic aneurysm and could play a role in the hemorrhagic and thrombotic events that can complicate the clinical development of these subjects.

Background: Many of the drugs used in the treatment of acute lymphoblastic leukemia in children may induce modifications in different organs and functions. Following the observation of a recurrent, mild delay in the prothrombin time in ALL children during maintenance chemotherapy, we explored the main parameters of the clotting function., Methods: 17 children with acute lymphoblastic leukemia were studied during maintenance chemotherapy for clotting function screening evaluation; 15 healthy children, matched for age and sex, were used as controls., Results: A uniform pattern of slight prolongation of the prothrombin time with significantly reduced levels of factors VII, IX, and a trend toward reduced activity of factor X was observed in the absence of any demonstrable anticoagulant factor., Conclusions: Antileukemic maintenance chemotherapy is associated with a subclinical modification of the clotting parameters that is not responsible for hemorrhagic diathesis. Long-term administration of anti-metabolites (6-mercaptopurine and methotrexate) could be responsible for this reversible impairment.

Purpura Fulminans and DIC were the main clinical manifestations of the antiphospholipid syndrome observed in a 62-year-old man. The patient was well until 44 years of age when he began to suffer from recurrent thrombophlebitis, without other symptoms suggestive of immune disease. At the time of hospital admission the pt. appeared acutely ill, showing high fever, severe anemia, massive urinary blood loss, multiple purpuric patches evolving to hemorrhagic bullae and gangrene rapidly spreading over about 30% of the total body area. No signs of neurological involvement or of visceral thrombotic occlusions were present. Clotting tests were consistent with a diagnosis of DIC, further confirmed by skin biopsy showing the presence of thrombi in dermal arterioles. The autoantibody research was positive as follows: Waaler-Rose 1:40, Anti-DNA 1:80; ANF 1:640, aCA IgG 100 GPL. LA was diagnosed according to standard criteria: prolonged KCT and RVVT not corrected by a mixture of normal plasma and abnormal TTI. Plasma exchange in association with heparin and prednisone was effective in arresting the progression of the skin lesion; nevertheless the patient died ten days after hospital admission for sepsi and acute renal failure.