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[Measurement of bleeding time and study of thrombocyte aggregation. Standardization of methods, normal values and results in patients with suspected hemorrhagic diathesis].

Bleeding time measurement and investigation of platelet aggregation in platelet rich plasma (PRP) are routine procedures for the diagnosis of defects in primary hemostasis. These tests are subject to methodological difficulties and should be well standardized in each individual laboratory. - In the present study, bleeding time was measured using the Simplate II device in 40 normal subjects. Furthermore, platelet aggregation in PRP induced by ADP, collagen, arachidonate, and ristocetin was examined. 26 patients referred for investigation of a suspected mild bleeding disorder, who had a normal plasmatic coagulation profile, a normal von Willebrand factor activity, and a normal platelet count, were similarly studied. - Based on the reference values established in the 40 normal subjects, platelet aggregation was found to be pathologic in 7 patients and normal in 12. In 7 patients platelet aggregation was considered to be borderline-pathologic as defined by the range of platelet aggregability found in the 10% of our normal subjects showing the weakest aggregation responses. Bleeding time was prolonged in only 3 patients whereas it was normal in the remaining 23. There was strong evidence of a hemostatic defect as assessed by systematic patient history in 6 out of 7 patients with pathologic platelet aggregation, but in only 3 out of 19 showing normal or borderline-pathologic aggregation. - Pathologic platelet aggregation, therefore, represents not only an abnormal laboratory finding but is likely to be associated with a hemorrhagic diathesis. Platelet aggregation studies do not permit etiologic diagnosis of the thrombocytopathy except for the well-defined membrane glycoprotein deficiencies. The bleeding time appeared to be of low sensitivity for the diagnosis of mild platelet dysfunction.

Adolescent↗

Spinal haematoma following epidural analgesia. Report of a patient with ankylosing spondylitis and a bleeding diathesis.

A patient who developed an epidural haematoma with multifactorial aetiology (bleeding diathesis, ankylosing spondylitis, chronic alcoholism and acute pancreatitis) after epidural analgesia for pain relief is described. Our conclusion is that adequate laboratory screening of blood coagulation, including platelet count, should be carried out in this category of patient before attempted epidural blockade, the risks of which must be weighed against the benefits. The block should be allowed to wear off intermittently and repeated neurological assessment performed if an epidural catheter is used for repeated injections or for a continuous infusion of local anaesthetic. Neuroradiological examination should be carried out promptly if an epidural haematoma is suspected and surgical decompression performed without delay if the diagnosis is confirmed.

Anesthesia, Epidural↗

Abnormal structure of von Willebrand factor in myeloproliferative syndrome is associated to either thrombotic or bleeding diathesis.

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the "in vivo" proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities. The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring "in vivo" rather than "in vitro", and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Deamino Arginine Vasopressin↗

Biochemical markers of tumor diathesis and early cancer.

Many biochemical parameters have been used as tumor markers but few are satisfactory to reflect tumor diathesis and/or for early detection. Studies in the Cancer Institute, Chinese Academy of Medical Sciences, have indicated that serum alpha 1-acid glycoprotein and sialic acid were increased in lung cancers, but 20% of pulmonary tuberculosis patients were also positive. Serum polyamines determined by RIA were increased in cancer patients. The positive rates for cancer of lung and esophagus were 84% and 100%, respectively. Polyamine contents considerably increased in esophagus tissue of rats treated with methylbenzylnitrosamine, and this occurred far earlier than the tumor appeared. However, whether serum polyamine can be used for early detection of esophageal cancer awaits further studies. An unknown fluorescent compound in urine was found in normal people but was very much decreased in cancer patients. This compound showed cytostatic effect on tumor cells in vitro. Serum antibodies against EBV-associated DNase could be used as a marker for NPC.

Animals↗

[Dietetic aspects of preventing urolithiasis in patients with gout and uric acid diathesis].

Patients suffering from gout and uric acid diathesis received a specialized diet containing 70 g protein (85% of plant protein including 20 g of soybean protein isolate), 85 g fat and 350 g carbohydrates. As a result there was an improvement of the general well-being during dietetic management, a rise of pH of the urine to normal, a decrease in the concentration of uric acid in blood serum and urine with a simultaneous elevation of the latter's clearance, an increase in glomerular filtration, a reduction in blood cholesterol content. The data obtained allow the conclusion to be made about the necessity of the rigid observance of the diet by the patients. This will play an important role both in the treatment and prophylaxis of urolithiasis in the patients' population under consideration.

Adult↗

A hemorrhagic diathesis with involvement of hypothalamus produced in rats by cyclophosphamide.

Large doses of cyclophosphamide caused a hemorrhagic diathesis related to bone marrow destruction and thrombocytopenia. Although several organs had hemorrhages, there was a striking predilection for the hypothalamus, ileum and mesentery of adult rats. The reasons for this localization are not known, but involvement of hypothalamus may be related to known functional effects of the drug on the neuroendocrine system. There were hemorrhages in choroid plexus, ciliary body and urinary bladder also, but these localizations were due to prior direct toxic injury to these structures by cyclophosphamide.

Animals↗

Fatal thrombocytopenic hemorrhagic diathesis associated with dapsone administration to a dog.

Dapsone was given for six days to a dog with chronic skin disease. The dog then became weak and anorectic, and it vomited and had purpura caused by severe thrombocytopenic hemorrhagic diathesis. Despite treatment, the dog died a week later. There were clinical and pathologic evidence that the dog's platelets and megakaryocytes had been destroyed during the first few days of dapsone therapy. It was concluded that the syndrome was dapsone-induced and that thrombocytopenia should be considered among the adverse reactions to dapsone in the dog.

Animals↗

Alpha-1-antitrypsin deficiency presenting as a bleeding diathesis in the newborn.

Three cases of alpha-1-antitrypsin deficiency are reported. Each infant presented in the newborn period with a haemorrhagic tendency which responded to vitamin K. Two of them subsequently developed cirrhosis, and Case 2 is one of the few reported cases in infantile cirrhosis associated with the heterozygous protease inhibitor (Pi) SZ phenotype. On the basis of these 3 patients we feel that the exclusion of alpha-1-antitrypsin deficiency by Pi phenotyping should be considered in any baby presenting with a bleeding diathesis, especially in view of the genetic implications of the homozygous Pi ZZ phenotype.

Hemorrhagic Disorders↗

[Hemorrhagic diathesis as a rare lead symptom in Addison-Biermer's anemia].

It is reported on a patient with Addison-Biermer's disease who was admitted to hospital under the diagnosis of a bleeding ventricle ulcer and in whom was detected a thrombocytopenic haemorrhagic diathesis. By means of injections of vitamin B12 a complete haematologic remission was achieved. The absence of a clear increase of reticulocytes as a sequel of the blood transfusions performed before the specific therapy is discussed.

Adult↗

[Panniculitis with cellular phagocytosis. Chronic form of histiocytic panniculitis with fever, pancytopenia, polyserositis and lethal hemorrhagic diathesis].

Two cases of what was originally called "Weber-Christian disease" were found to be a chronic, recurrent form of histiocytic panniculitis characterized by histiocytic engulfment of red and white blood cells--"cytophagocytosis." The disease was manifested by recurrent fever, subcutaneous nodules, pancytopenia, and mucosal ulcerations. Hepatosplenomegaly and enlarged lymph nodes were observed. Focal invasion of the reticuloendothelial system by acidophilic or cytophagic histiocytes could be identified. Progressive changes in liver function and hemorrhagic diathesis occurred in both patients.

Adipose Tissue↗

[Case reports of hemorrhagic diathesis in calves with bovine diarrhea virus infection].

Clinical and pathological findings in six veal calves suffering from haemorrhagic diathesis are reported. Further pathological and virological results were highly suggestive of mucosal disease (BVD). No virus isolation or classification was possible. The post mortem results indicated that the virus might have been cytopathogenic. The cases are discussed and compared with similar field and experimental publications dealing with thrombocytopenia in veal calves in the USA. These are the first reports of cases published in Germany.

Animals↗

Low prevalence of the factor V Leiden mutation among "severe" hemophiliacs with a "milder" bleeding diathesis.

Patients with hemophilia A and B and factor levels than 1 percent of normal bleed frequently with an average number of spontaneous bleeding episodes of 20-30 or more. However there are patients with equally low levels of factor VIII or factor IX who bleed once or twice per year or not at all. To examine whether the presence of a hereditary defect predisposing to hypercoagulability might play a role in ameliorating the hemorrhagic tendency in these so-called "mild severe" hemophiliacs, we determined the prevalence of prothrombotic defects in 17 patients with hemophilia A and four patients with hemophilia B selected from 295 and 76 individuals with these disorders, respectively, followed at a large Italian hemophilia center. We tested for the presence of the Factor V Leiden mutation by PCR-amplifying a fragment of the factor V gene which contains the mutation site and then digesting the product with the restriction enzyme MnlI. None of the patients with hemophilia A and only one patient with hemophilia B was heterozygous for Factor V Leiden. None of the 21 patients had hereditary deficiencies of antithrombin III, protein C, or protein S. Our results indicate that the milder bleeding diathesis that is occasionally seen among Italian hemophiliacs with factor levels that are less than 1 percent cannot be explained by the concomitant expression of a known prothrombotic defect.

Factor V↗

Do ulcers burn out or burn on? Managing duodenal ulcer diathesis in the Helicobacter pylori era. Ad Hoc Committee on FDA-Related Matters.

Now that the Food and Drug Administration is examining various treatment regimens for eradication of Helicobacter pylori (H. pylori) infection, the question of whom to treat has come to the forefront. Widespread attempts to eradicate the bacterium are not without risk, including the possibility of accelerating the emergence of resistant strains of the organism, in addition to possible adverse events of agents used to cure the infection. These risks are of concern to the Agency in the process of granting marketing approvals for various therapies. The association of H. pylori and duodenal ulcer (DU) is no longer disputed; however, data to date have been generated in studies of patients with active (acute) DU. In these patients, the benefits of eradication therapy are clear. Patients with a documented history of DU who do not have an ulcer crater at the time of presentation have not been well studied in controlled trials. If they are at similar risk for recurrence and complications, it follows that they, too, should be candidates for H. pylori testing and treatment. However, if, as some believe, duodenal ulcer disease becomes "inactive" or "burns out" with time, an argument could be made for expectant treatment for this subgroup of patients. The present review examines the available literature on the natural history of DU disease and explores the validity of the hypothesis of duodenal ulcer "burn out." Analysis of the data shows that there is little support for the phenomenon of duodenal ulcer disease "burn out," and that, in fact, DU disease resulting from H. pylori infection is a chronic, relapsing condition, lasting for decades, if not a lifetime. The literature is compatible with the view that, in the majority of patients, DU occurs on a background of an "ulcer diathesis" that is fueled by H. pylori infection, and "burns on, not out", until and unless the infection is extinguished. The true incidence of ulcer relapse is difficult to predict due to the common occurrence of asymptomatic ulcers and the poor correlation of symptoms with the presence of ulcer. Therefore, treatment of patients with a history of duodenal ulcer disease should be advocated, even if their ulcer disease is not "active," because the risk of recurrence and complications does not diminish unless the H. pylori bacterium is eradicated.

Acute Disease↗

Severe haemorrhagic diathesis in an adult patient with cystic fibrosis after long-term antibiotic treatment of pulmonary infection.

We describe the case of a 22 yr old male patient with cystic fibrosis, who, after long-term antibiotic treatment of pulmonary infection, developed a haemorrhagic diathesis with severe bleeding from the mucus membrane of the mouth, and haematuria. Rapid recovery was observed after infusion of vitamin K. During 8 months of follow-up, no evidence of recurrence of the clotting disturbances and anaemia were noted. The combination of impaired absorption of vitamin K due to underlying disease with the antibiotic-induced suppression of vitamin K synthesis by intestinal bacteria could be a possible explanation for this disorder.

Adult↗

Prediction of bleeding diathesis in patients undergoing cardiopulmonary bypass during cardiac surgery: viscoelastic measures versus routine coagulation test.

BACKGROUND: Severe hemorrhagic tendency often complicates cardiopulmonary bypass (CPB) in cardiac surgery. In this study, we compared the effectiveness of thromboelastography (TEG), Sonoclot (SCT), and routine coagulation test (RCT) in the prediction of coagulation defects. METHODS: Forty-three patients undergoing cardiac surgery with CPB were included. Blood for RCT, TEG, and SCT profiles was sampled before systemic heparinization and after protamine administration. Clinically significant bleeding was defined as chest tube drainage in excess of 100 ml/h for 3 consecutive hours or 300 ml/h in 1 h. All coagulation parameters obtained before and after CPB were compared. The sensitivity, specificity, accuracy, false positive, and false negative rate were also calculated and compared. RESULTS: All coagulation tests were within normal range except higher partial thromboplastin time. Variables which were significantly different from those before CPB included platelet count, fibrinogen level, prothrombin time, and thrombin time in RCT, alpha angle and maximum amplitude in TEG, and R2 and peak time in SCT. In the TEG tracing, all variables had high sensitivity, specificity, and accuracy (average 85.4%, 83%, and 83.5% respectively) and low false positive and negative rate (12.5% and 5% respectively). Although SCT had high sensitivity (76.3%) and low false negative rate (6.5%), its specificity and accuracy were all under 50%. CONCLUSIONS: Our data demonstrated that the TEG monitoring is a useful tool for detecting post-CPB bleeding diathesis and can provide much predictive information. RCT and SCT are of limited value because of higher rate of unreliable results.

Blood Coagulation Tests↗