1/53. Anaemia, thrombocytopenia and coagulopathy due to occult diffuse infantile haemangiomatosis of spleen and pancreas.Diffuse infantile haemangiomatosis of the spleen is a very rare lesion. Large haemangiomas may cause trapping of platelets and coagulation disorders known as Kasabach-Merrit syndrome. We here report the case of an infant with splenic and pancreatic haemangiomatosis presenting with life-threatening thrombocytopenia, anaemia and intravascular coagulation. diagnosis was hampered by reactive erythroblastosis and non-conclusive radiological findings. While treatment with corticosteroids was ineffective, administration of antithrombin III improved coagulation parameters. After splenectomy the child recovered promptly and has remained free of disease for 3 years to date. CONCLUSION: Occult visceral haemangiomatosis without visible cutaneous haemangiomas should be included in the differential diagnosis of thrombocytopenia, anaemia and consumption coagulopathy. Antithrombin III treatment may be considered to overcome bleeding problems in patients with Kasabach-Merrit syndrome.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
2/53. Reduced nitric oxide production by L-arginine deficiency in lysinuric protein intolerance exacerbates intravascular coagulation.Lysinuric protein intolerance (LPI) results in low serum L-arginine, hyperammonemia, mental retardation, thrombocytopenia, and an increased frequency of bowel movements. Our objective was to evaluate the effects of low serum L-arginine, the essential substrate for reactions catalyzed by nitric oxide synthetase (NOS), on the serum nitric oxide (NO) level and coagulation activity in a patient with LPI. A 37-year-old Japanese man who presented with abdominal pain and subnormal fasting levels of serum L-arginine and L-lysine was found to have LPI. The result of oral administration of diamino acids was an increased in urine and a decrease in serum, thus confirming the diagnosis. A decrease in the platelet count and an increase in the plasma levels of thrombin-antithrombin III complex (TAT) and fibrin degradation products (FDPs) indicated the presence of subclinical intravascular coagulation. serum levels of NO derivatives and L-arginine were determined after intravenous administration of L-arginine. The effects of intravenous L-arginine or transdermal nitroglycerin on the plasma level of TAT were also investigated. serum levels of NO derivatives were significantly reduced in the LPI patient versus the healthy control group (n = 5). Intravenous administration of L-arginine increased the serum level of NO derivatives and the platelet count and reduced plasma TAT and FDP levels. The plasma level of TAT was also reduced by transdermal nitroglycerin. A decrease in the serum level of L-arginine in patients with LPI appears to result in a decrease in NO production. The improvement in plasma TAT levels produced by administration of intravenous L-arginine or transdermal nitroglycerin suggests that intravascular coagulation is exacerbated by the decrease of NO production in patients with LPI.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
3/53. Cerebral venous sinus thrombosis associated with hepatic cirrhosis.Cerebral venous sinus thrombosis is not a recognized complication of end-stage liver disease. A case of sagittal sinus thrombosis in a 44-year-old male with end-stage hepatic cirrhosis is described. Recurrent seizures were the only manifestation. work-up revealed severe deficiency of protein C, protein s, and antithrombin III. He was treated with low molecular weight heparin and underwent an orthotopic liver transplant after three months. Follow-up helical CT venogram showed resolution of the sinus thrombosis.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
4/53. Is there a possible role for haemostasis in the development of perigraft reaction complicating the modified Blalock Taussig shunt?The perigraft reaction is an unusual complication found in patients in whom a modified Blalock Taussig shunt has been created using a polytetrafluoroethylene graft. We found that, in two infants, consistent laboratory findings during such a perigraft reaction were hypofibrinogenemia, increased levels of thrombin-antithrombin III complex, prothrombin fragment 1 and 2 and products of degradation of fibrin. Normalization of the levels of fibrinogen produced resolution of the perigraft reaction.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
5/53. Successful anticoagulation with hirudin in a patient with mesenteric venous thrombosis and multiple coagulation abnormalities.A case of multiple thrombotic diatheses discovered in the setting of mesenteric venous infarction is discussed. The patient had deficiencies of protein C, protein s, antithrombin III; was heterozygous for factor V Leiden; and had polycythemia vera. Adequate anticoagulation could not be established with heparin administration and hirudin was used. The diagnosis of mesenteric venous infarction, thrombotic tendency of multiple coagulation diatheses, and use of hirudin are discussed.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
6/53. Autoantibody against prothrombin aberrantly alters the proenzyme to facilitate formation of a complex with its physiological inhibitor antithrombin III without thrombin conversion.Acquired coagulation factor inhibitors include pathologic immunoglobulins that specifically bind to coagulation factors and either neutralize their procoagulant activity, accelerate their clearance from the circulation, or have proteolytic activity to degrade them into inactive polypeptides. Here, an autoantibody against prothrombin is described in a patient with serious hemorrhagic diatheses. The autoantibody exerts its influence by a previously unknown mechanism in which it inhibits coagulation through aberrant activation of the proenzyme in a catalytic manner. The antibody-bound prothrombin formed a stable stoichiometric complex with antithrombin III, consisting of intact prothrombin and an antithrombin III molecule cleaved at the (393)Arg-(394)Ser bond. The antibody dissociated from prothrombin after the complex formation with antithrombin III. Although the bound antibody elicited protease activity from prothrombin, the complex was not able to convert fibrinogen to fibrin or to activate protein C. Thus, this is the first description of an autoantibody that induces protease-like activity from a human proenzyme, permitting subsequent neutralization by its physiological inhibitor. (blood. 2001;97:3783-3789)- - - - - - - - - - ranking = 7keywords = antithrombin (Clic here for more details about this article) |
7/53. Venous limb gangrene during warfarin treatment of cancer-associated deep venous thrombosis.BACKGROUND: The cause of cancer-associated venous limb gangrene is unknown but could paradoxically be due to warfarin. OBJECTIVE: To determine the pathogenesis of venous gangrene in a patient with cancer. DESIGN: Case report. SETTING: University hospital in ontario, canada. PATIENT: 66-year-old woman with metastatic lung cancer and deep venous thrombosis. MEASUREMENTS: Levels of vitamin k-dependent factors, additional coagulation factors, and thrombin-antithrombin complexes (marker of thrombin generation). RESULTS: During warfarin use, venous limb gangrene developed when the international normalized ratio (INR) reached 6.0 (therapeutic range, 2.0 to 3.0); at this time, the level of protein C (a vitamin k-dependent natural anticoagulant) was severely reduced, but thrombin-antithrombin complexes remained markedly elevated. The supratherapeutic INR was explained by the greatly reduced levels of factor vii, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity. CONCLUSION: warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein C while at the same time failing to reduce thrombin generation.- - - - - - - - - - ranking = 2keywords = antithrombin (Clic here for more details about this article) |
8/53. Anticoagulation management in a patient with an acquired antithrombin iii deficiency.We report a case of heparin resistance and its management during cardiopulmonary bypass (CPB). A 63-year-old, 96 Kg female with a posterior myocardial infarction (MI) with previous deep venous thrombosis was treated with intravenous (IV) heparin infusion for 7 days before myocardial revascularization surgery. The patient required 1200 IU/Kg of beef lung heparin to extend the activated clotting time (ACT) in order to initiate CPB. A total of 1562 IU/Kg of heparin was administered throughout the procedure. This acquired heparin resistance was attributed to an antithrombin (AT III) deficiency, and was treated with fresh frozen plasma (FFP) to restore adequate anticoagulation. The patient's heparinized ACTs ranged between 368 seconds and 387 seconds before FFP administration as opposed to 626 seconds to 1329 seconds after treatment with FFP and additional heparin once on CBP. The patient experienced an uneventful postoperative course. Future treatment with AT III concentrate rather than FFP may reduce heparin requirements that will, in turn, reduce protamine reversal dose, postoperative bleeding attributable to heparin rebound, and its associated complications.- - - - - - - - - - ranking = 5keywords = antithrombin (Clic here for more details about this article) |
9/53. Haemostatic effects in vivo after snakebite by the red-necked keelback (Rhabdophis subminiatus).We describe a patient who developed a severe coagulopathy after being bitten by a red-necked keelback snake (Rhabdophis subminiatus), a species which is generally considered non-venomous. The patient's blood was incoagulable due to complete depletion of fibrinogen. Comprehensive coagulation studies were performed to identify the mechanism(s) by which the snake toxin caused the coagulopathy. It was found to contain a potent prothrombin activator, probably an activator of protein C and possibly also a factor X activating enzyme. The fibrinolysis was secondary to intravascular fibrin formation; there were no indications for a direct fibrinogenolytic activity in the snake toxin. Remarkably, there was virtually no consumption of antithrombin III, despite extensive thrombin formation; this feature appears to be not uncommon after snake bites, but is still unexplained.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
10/53. Met 358 to Arg mutation of alpha 1-antitrypsin associated with protein c deficiency in a patient with mild bleeding tendency.The molecular defect responsible for a dramatic prolongation of all standard clotting tests discovered in a 15-yr-old boy has been identified. Initial investigations revealed the presence of an activated Factor X (factor xa) and thrombin inhibitor which copurified with alpha 1-antitrypsin (alpha 1-AT), thereby suggesting the occurrence of an alpha 1-AT variant similar to alpha 1-AT Pittsburgh. This was confirmed by dot-blot analysis and direct sequencing after amplification by the polymerase chain reaction. A G to T transition at nucleotide 10038 results in the substitution of Met to an Arg, converting alpha 1-AT into an Arg-Ser protease inhibitor (serpin) that inhibited thrombin and factor xa more effectively than antithrombin III. Surprisingly, there was no bleeding history in the proband. The common mutation Z, which may explain a reduced expression of the allele bearing the Arg 358 Met mutation, was not observed in the propositus' dna. To exclude the presence of another mutation, the coding regions and intron/exon junctions were sequenced. No other mutation was found. Recently, the patient experienced his first hemorrhagic episode at the age of 17. The level of the abnormal inhibitor had increased twofold 2 mo before. The large decrease in protein C concentration may account for the mild bleeding tendency in this case, despite the presence of the alpha 1-AT Pittsburgh mutation. An abnormal protein C pattern was observed in patient's plasma, suggesting that the circulating deficiency might be due to a deleterious effect of the abnormal inhibitor on both intracellular processing and catabolism of protein C.- - - - - - - - - - ranking = 1keywords = antithrombin (Clic here for more details about this article) |
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