1/130. leukostasis followed by hemorrhage complicating the initiation of chemotherapy in patients with acute myeloid leukemia and hyperleukocytosis: a clinicopathologic report of four cases.BACKGROUND: Pulmonary and cerebral leukostasis, or parenchymal hemorrhage in these organs, are well-known early complications developing in patients with acute myeloid leukemia (AML), particularly when myelomonocytic features, hyperleukocytosis, and/or a coagulation disorder are initially present. Commonly, these complications arise during increasing leukocyte counts (WBCs). methods: The authors describe four patients with AML and hyperleukocytosis who developed leukostasis followed by parenchymal hemorrhage. RESULTS: Bleeding in all patients occurred while their WBCs were decreasing following cytosine-arabinoside chemotherapy, and in the absence of disseminated intravascular coagulation or severe thrombocytopenia. Radiologic and histopathologic findings underscoring possible mechanisms are presented in the article. CONCLUSIONS: Alterations of cell adhesion associated with chemotherapy-induced blast lysis or cellular differentiation are possible factors contributing to this particular sequence (cytosine arabinoside-based chemotherapy, leukostasis, and subsequent hemorrhage). Prophylactic measures for managing this early complication of AML treatment include leukapheresis to reduce the WBC prior to the initiation of chemotherapy.- - - - - - - - - - ranking = 1keywords = count (Clic here for more details about this article) |
2/130. Fibrinogens Bern IV, Bern V and Milano XI: three dysfunctional variants with amino acid substitutions in the thrombin cleavage site of the Aalpha-chain.Thrombin-induced cleavage of fibrinopeptide a is the initial step in the conversion of fibrinogen to fibrin. Three dysfunctional fibrinogen variants are described with an amino acid substitution at position 16 of the Aalpha-chain: the fibrinogen variants Bern IV and Milano XI having an Arg-->His substitution and the variant Bern V having an Arg-->Cys substitution. Routine coagulation studies revealed prolonged plasma thrombin and reptilase clotting times in all patients, and a discrepancy between the plasma levels of fibrinogen determined by the clotting assay and electroimmunoassay. The defect was localized by high-performance liquid chromatography analysis of fibrinopeptide release and confirmed by polymerase chain reaction and sequencing of exon 2 of the Aalpha-chain. immunoblotting analysis with a rabbit antiserum against human serum albumin indicated that albumin was linked to the additional sulfhydryl group of fibrinogen Bern V. The assay of tissue-plasminogen-activator-induced plasmic degradation revealed that the fibrinolysis of fibrin Bern V was delayed, whereas fibrin Bern IV was digested in the same way as normal fibrin.- - - - - - - - - - ranking = 0.10818315764176keywords = assay (Clic here for more details about this article) |
3/130. Clinical and physiologic studies of two siblings with prekallikrein (Fletcher factor) deficiency.Two siblings with hereditary Fletcher factor (prekallikrein) deficiency were studied for alterations of fibrinolysis, platelet function, skin inflammatory responses, permeability factor (PF/dil) formation and leukocyte chemotaxis. In vivo stimulation of fibrinolytic activity was normal; the bleeding time and platelet functions (adhesivity, aggregation, release reaction) were also normal. Both immediate (wheal-flare reaction to histamine, bradykinin, prostaglandin E1, physical agents) and delayed sensitivity skin test reactions were within normal limits. Migration of subjects' leukocytes to attractants in skin windows and in Boyden-type chambers was the same as that of control leukocytes. Serum complement components were essentially normal. One subject's leukocytes showed normal tissue factor production on stimulation by endotoxin, although prekallikrein deficiency did impair the endotoxin-stimulated generation of serum procoagulant activity. PF/dil caused increased vessel permeability in human skin; in vitro generation of PF/dil required both the Hageman factor and prekallikrein. The Fletcher factor-deficient subjects responded in a normal manner to PF/dil. Based on the Fletcher factor-coagulation assay, the biologic half-disappearance time of prekallikrein (after the transfusion of normal plasma in one of the subjects) was estimated at 35 hours. Therefore, these studies suggest that severe prekallikrein (Fletcher factor) deficiency in man is not associated with any clinically significant impairment in hemostasis, fibrinolysis, inflammatory responses or leukocyte function.- - - - - - - - - - ranking = 0.036061052547255keywords = assay (Clic here for more details about this article) |
4/130. Bleeding disorder with abnormal wound healing, acid-soluble clots and normal factor XIII.An unusual bleeding disorder clinically resembling factor xiii deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of a pepsin-like plasma protease which is activated at low pH. Asystematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor xiii deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.- - - - - - - - - - ranking = 0.036061052547255keywords = assay (Clic here for more details about this article) |
5/130. 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 = 2keywords = count (Clic here for more details about this article) |
6/130. ciprofloxacin-warfarin coagulopathy: a case series.ciprofloxacin, when given to patients previously anticoagulated with warfarin, can occasionally cause an exaggerated hypoprothombinemic response and bleeding diatheses. Two such cases encountered at our institution are presented and data is combined with 64 cases reported to the food and Drug Administration's (FDA) Spontaneous Reporting System (SRS) database, which included all cases reported from 1987 through 1997. Of 66 total cases the median age was 72 (range 36-94). The mean time to detection of the coagulopathy following the ciprofloxacin challenge was 5.5 days (n = 50). hospitalization was reported in 15 cases, bleeding in 25 cases, and death in one case. The median prothrombin time (PT) and international normalized ratio (INR) was 38.0 (n = 13) and 10.0 (n = 23), respectively. The mean number of medications taken was 6.5 (n = 45). The mean time to correction was significantly shorter between the treated (2.5 days) and the untreated (4.0 days) groups (P < 0. 008). The ciprofloxacin-warfarin coagulopathy occurred most commonly in patients in their seventh decade and in those who require polypharmacy. Active treatment of the coagulopathy results in more rapid resolution than observation alone. Clinicians should be aware of the potential bleeding complications that can occur with the ciprofloxacin-warfarin drug-drug interaction.- - - - - - - - - - ranking = 1keywords = count (Clic here for more details about this article) |
7/130. Defective fibrinogen polymerization associated with a novel gamma279Ala-->Asp mutation.A woman with menorrhagia was investigated for a suspected fibrinogen mutation when coagulation tests revealed prolonged thrombin (55 s) and reptilase (43 s) times together with a functional and an antigenic fibrinogen concentration of 0.7 and 2.8 mg/ml respectively. Heterozygosity for a gamma-chain mutation was suggested by a doublet gamma band on SDS-PAGE and an increased negative charge was observed on isoelectric focusing of HPLC-isolated gamma-chains. Electrospray ionization mass spectrometry revealed a gamma-chain mass of 48 411 Da, which was 20 Da more than the control value of 48 391 Da. Because the normal and variant gamma-chains were not resolved, this implied a 40-Da increase in 50% of the gamma-molecules. An increased negative charge and a 44-Da increase in mass was verified when dna sequencing showed heterozygosity for an Ala (GCC)-->Asp (GAC) substitution at codon 279 of the gamma-gene. Fibrin polymerization curves indicated a delay in the onset, and a decrease in the rate, of polymerization. Examination of crystal structures showed that the adjacent Tyr-gamma280 side chain is involved in bonding across the D-D interface, and from the proximity of the gamma279Ala-->Asp mutation it would appear that this perturbs the end-to-end DD interactions between fibrin units of the growing polymer.- - - - - - - - - - ranking = 0.002973785204156keywords = unit (Clic here for more details about this article) |
8/130. Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome.A 3 year and 9 month-old girl presented with gingival bleeding, epistaxis, and multiple haematomas 3 days after an acute episode of gastroenteritis. prothrombin time and activated partial thromboplastin time were prolonged with reduced clotting activity of factor II (< 10%), VIII (<1%), IX (3%), XII (10%) and evidence of a high titre inhibitor. Prothrombin (factor II) level was below the detection limit, both in a functional and immunological assay. It did not increase after administration of vitamin k or fresh frozen plasma. Further studies revealed presence of a strong lupus anticoagulant and a specific IgG antibody against prothrombin. factor viii antigen levels also were reduced (31%), but to a lesser extent than functionally determined factor viii (<1%). blood coagulation normalised following clinical recovery 6 weeks after admission. The pathophysiology of this acquired inhibitor phenomenon (accelerated clearance of complexes of clotting factors and phospholipids) is discussed. CONCLUSION: The haemorrhagic lupus anticoagulant syndrome (acquired hypoprothrombinaemia lupus anticoagulant syndrome) is a rare presentation of acquired bleeding diathesis in childhood. Since most cases in post-infectious children are asymptomatic, it might be underdiagnosed. In children with newly appearing bleeding symptoms or unclear prolonged prothrombin time or activated partial thromboplastin time, one has to consider this syndrome which could lead to relevant bleeding.- - - - - - - - - - ranking = 0.036061052547255keywords = assay (Clic here for more details about this article) |
9/130. Spontaneous inhibitors to coagulation factors.Spontaneous inhibitors to coagulation factors are autoantibodies that usually appear in the elderly, but may also occur in patients with immunological disorders such as lupus, lymphoma, asthma or drug reactions. Most antibodies are directed against factor viii, but any coagulation protein may be affected. They should be suspected in individuals who previously had normal haemostasis, but who now begin to experience bleeding into the skin and muscles, or suffer haemorrhages after routine procedures such as insertion of vascular catheters, intramuscular injections, or minor surgery. The haemostasis laboratory is critical in identifying the particular inhibitor and quantitating its potency. factor viii inhibitors prolong the partial thromboplastin time (PTT) but not the prothrombin time (PT), and incubating mixtures of patient plasma and normal plasma enhances the prolongation of the clotting time. The Bethesda assay provides a rough assessment of inhibitor potency. Inhibitors of von willebrand factor prolong the bleeding time and impair ristocetin-induced platelet aggregation. Factor V inhibitors are associated with a prolonged PTT and PT, not correctable with normal plasma. patients will often have a history of exposure to bovine thrombin in fibrin glue. The antibodies most difficult to recognize are those that alter fibrin polymerization or stabilization. Abnormal clot retraction or clot solubility in urea solutions are an important clue. The management of these disorders depends on characterization of the inhibitor, and using appropriate clotting factor concentrates to control acute bleeding. For example, recombinant human factor viii or desmopressin may be effective for patients with low titre factor viii inhibitors, whereas porcine factor viii, recombinant factor Vlla, or prothrombin complex concentrates stem bleeding in those with high titres. Inhibitors of von willebrand factor may be amenable to desmopressin, cryoprecipitate, or von willebrand factor concentrates. Some patients with factor V inhibitors have responded to platelet transfusions, as the platelet factor V may be shielded from the autoantibody. Bleeding due to factor XIII inhibitors may be managed with fibrogammin, a factor XIII concentrate. All patients should be treated for underlying disorders and given drugs such as corticosteroids and cytotoxic agents to suppress inhibitor formation. Major advances in new immunosuppressive technologies, such as monoclonal B-cell antibodies, offer hope of more effective therapies for spontaneous inhibitors to coagulation factors.- - - - - - - - - - ranking = 0.036061052547255keywords = assay (Clic here for more details about this article) |
10/130. amniotic fluid embolism and isolated coagulopathy: atypical presentation of amniotic fluid embolism.A 41-year-old multigravida presented at 32 weeks of gestation with polyhydramnios and an anencephalic fetus. Abnormal bleeding as a result of disseminated intravascular coagulation complicated an emergency Caesarean section for severe abdominal pain thought to be due to uterine rupture. Massive transfusion with blood products was necessary and the abdomen packed to control bleeding. The patient was transferred to the intensive care unit where she made a slow but complete recovery. amniotic fluid embolism with atypical presentation of isolated coagulopathy is the likely diagnosis in this case. The case serves to demonstrate that amniotic fluid embolism may present with symptoms and signs other than the classical pattern of dyspnoea, cyanosis and hypotension.- - - - - - - - - - ranking = 0.002973785204156keywords = unit (Clic here for more details about this article) |
| | Next -> |