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Haemostatic activity of ethamsylate and aminocaproic acid adsorbed poly(2-hydroxyethyl methacrylate) particles.

A haemostatic material suitable for embolization was prepared by the adsorption of haemostatics--ethamsylate and aminocaproic acid in the spherical particles of porous poly(2-hydroxyethyl methacrylate) (p(HEMA)). The degree of purification of ethamsylate-treated particles was tested by an analysis of donor blood in contact with the material. An evaluation of the haemostatic properties of these materials was obtained by the determination of the indicators of blood clotting: activated partial thromboplastin time, thrombin time, and prothrombin time. Ethamsylate or aminocaproic acid-containing p(HEMA) has a distinct haemostatic effect on pathological blood of patients suffering from focal alterations of the liver. These haemostatic emboli materials show promise for the immediate control of various haemorrhages; when introduced into a zone with increased haemorrhage, they may help to correct disturbed haemostasis.

Adsorption↗

Effects of various doses of latamoxef (moxalactam) on haemostasis.

The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses.

Bleeding Time↗

The effect of L-asparaginase on antithrombin, plasminogen, and plasma coagulation during therapy for acute lymphoblastic leukemia.

Hemostatic function was studied sequentially in 12 children receiving L-asparaginase, vincristine, and prednisone as remission induction chemotherapy for acute lymphoblastic leukemia. The three-week period of L-asparaginase therapy was characterized by progressive decreases in plasma antithrombin, plasminogen, and fibrinogen concentrations, and by progressive increases in plasma clotting times (prothrombin time, partial thromboplastin time, thrombin time). Platelet counts rose rapidly during the third and fourth weeks of therapy as bone marrow remission was achieved. Factor V levels increased steadily during a five-week period, perhaps related to vincristine or prednisone therapy. Recent reports of thrombosis and hemorrhage in children and adults receiving L-asparaginase may be explained by this complex set of abnormalities in coagulation and coagulation control.

Adolescent↗

Preoperative evaluation of hemostasis in patients with congenital heart disease.

The incidence of abnormal results of coagulation tests and the risks for postoperative hemorrhage were assessed in 235 patients with congenital heart disease. Preoperatively, the prothrombin time, partial thromboplastin time, activated partial thromboplastin time, thrombin time, or platelet count was abnormal in 45 of the 235 patients (19%), a significantly higher incidence than that expected in a normal population (P less than 0.002). Prolonged values for the prothrombin time or the partial thromboplastin time or activated partial thromboplastin time were seen most frequently. Further evaluation in eight of the patients with prolonged prothrombin time or partial thromboplastin or activated partial thromboplastin time showed decreased levels of either factor VII or IX in six of them, suggesting that impaired vitamin K-dependent carboxylation is commonly present. Normal results of preoperative coagulation tests do not exclude the presence of a major bleeding diathesis (von Willebrand's disease was later diagnosed in a patient with such findings). The use of blood products during subsequent cardiac operations was not significantly different in patients with normal or abnormal test results. Two of the three patients who required reoperation and were found to have a nonsurgical cause of bleeding had abnormalities in two or more of the preoperative coagulation tests. This finding suggests that abnormal results of preoperative coagulation tests may be predictive of defective hemostasis in the postoperative period.

Adolescent↗

Hemocompatibility of titanium oxide films.

Hemocompatibility is a key property of biomaterials that come in contact with blood. Surface modification has shown great potential for improving the hemocompatibility of biomedical materials and devices. In this paper, we describe our work of improving hemocompatibility with Ti-O thin films prepared by plasma immersion ion implantation and deposition and by sputtering. The structure and surface chemical and physical properties of the films were characterized by X-ray diffraction, Auger electron spectroscopy, atomic force microscopy (AFM), contact angle measurement, and Hall effect measurement. The behavior of fibrinogen adsorption was investigated by 125I radioactive isotope labeling and AFM. Systematic evaluation of hemocompatibility, including in vitro clotting time, thrombin time, prethrombin time, platelet adhesion, and in vivo implantation into dog's ventral aorta or right auricle from 17 to 90 days, proved that Ti-O films have excellent hemocompatibility. It is suggested that the significantly lower interface tension between Ti-O films and blood and plasma proteins and the semiconducting nature of Ti-O films give them their improved hemocompatibility.

Adsorption↗

Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion.

Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion.

Adrenal Cortex Hormones↗

Gel chromatography of heparin.

It is assumed that heparin is a heterogeneous substance. In order to further investigate the purification of heparin, a column chromatographic technique for the fractionation of heparin is described using various diameters of bead form cross-linked dextran gels and an automated apparatus. It was observed that Sephadex G-50 resulted in the separation of three well formed peaks and provided superior resolution compared to all other gels. One of the peaks, representing 51% of the original material, possessed strong anticoagulant activity as measured by the recalcification time, partial thromboplastin time, thrombin time and the anti-Xa test. This peak also possessed strong metachromasia after electrophoresis as well as having a very potent anticoagulant effect in vivo. This technique may have a significant role in the purification of this agent from tissue sources.

Animals↗

[Peri- and postoperative use of low molecular weight heparin in peripheral vascular surgery].

A pilot study has been conducted in ten consecutive patients undergoing femoro-popliteal reconstruction or distal vascular surgery under epidural anaesthesia. Immediately before arterial cross-clamping, enoxaparin (E) (75 anti-Xa IU.kg-1) was injected intravenously (i.v.). During surgery, washing of the saphenous or polytetrafluoroethylene (PTFE) graft has been performed using enoxaparin. Enoxaparin (75 anti-Xa IU.kg-1) was administered subcutaneously (S.C.) 8 hours after the i.v. injection, and then every 12 hours during 10 days. The patency of the vascular reconstruction and the side-effects of E administration were evaluated clinically before and during surgery, then by a daily clinical examination. Echo-Doppler and/or arteriography were also performed preoperatively and on the 10th postoperative day. Haematocrit, platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and anti-Xa activity were assessed. None of the patients developed venous or arterial thrombosis and all the by-pass grafts remained patient. Only one minor surgical bleeding occurred on the first post operative day, despite anti-Xa levels in the expected range. One patient developed minor haematomas at the injection site. No bleeding was observed. Further randomized studies comparing LMWH and UH are required in order to substantiate these preliminary clinical and biological findings.

Aged↗

Bleeding and coagulation disorders in the elderly.

Ageing does not bring with it any major changes in the coagulation or fibrinolytic proteins or platelets. It does bring a greater burden of disease, with less reserves, and so when haemorrhage occurs in the elderly it has more serious consequences. The cause of a bleeding diathesis can usually be determined after a careful history, and examination of the patient followed by simple tests--the platelet count, blood film, bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and the euglobulin clot lysis time. Other confirmatory tests, assays and inhibitor titres, will seal the diagnosis. Treatment is mainly directed at removing the underlying cause, if possible, and remedying the defect, with platelet transfusion, fresh frozen plasma or factor concentrates. These treatments will not be effective where there is an inhibitor or antibody present; steroids, splenectomy (for ITP), plasma exchange or immunosuppression are needed. Two major advances have occurred in the early 1980s. One has been the introduction of high-dose intravenous immunoglobulin in the management of ITP, although worries remain about thrombotic events in elderly patients. The other is the spreading use of DDAVP, originally introduced for von Willebrand's disease and mild haemophilia, and now finding a role in uraemia and with cardiopulmonary bypass. Drugs are a significant and potentially preventable cause of bleeding in the elderly. The most frequent problems arise with anticoagulants. The risk of interactions increase with the number of other medications which are prescribed.

Aged↗

[Influence of cytostatic combination therapy with vincristine sulphate and iphosphamide on blood coagulation].

Disorders of blood coagulation were investigated before and during a cytostatic combination therapy with vincristine sulphate and iphosphamide (Asta Z 4942) in 12 patients with malignant tumours or haemoblastoses. Thromboplastin time, partial thromboplastin time, thrombin time, heat-dependent fibrin, clot retraction, and clotting factors II, V, VIII, IX, X, and the platelet count were determined. A change in the plasmatic coagulation system attributable to the combination therapy could not be demonstrated in any patient. The influence of the cytostatic combination on the platelet-dependent haemostasis was small; a decrease in platelet count could be observed in only one patient, in whom an additional causative damage to thrombopoiesis due to the underlying disease could be assumed. Regardless of the cytostatic therapy there were indications of a hypercoagulability in 10 patients. This explains the increased susceptibility of such patients for thromboses or consumption coagulopathy.

Adult↗

[Prevention of thromboembolism in hysterectomies with low molecular weight heparin Fragmin].

In comparison to standard heparins, the low-molecular types are said to have equal or better antithrombotic action and--since they affect coagulation less--to induce fewer hemorrhage complications. As they have a longer biologic half-life, a single subcutaneous injection per day is sufficient. In a prospective randomized study patients who had undergone vaginal and abdominal hysterectomy were given either the low-molecular heparin Fragmin (n = 95) or a combination of heparin-dihydergot (n = 98) as prophylaxis against thrombosis. Dosages of Fragmin were 2 X 2500 anti-Xa units on the day of surgery (Day 1) and 1 X 5000 anti-Xa units from Days 2 to 8; the dosage of heparin-dihydergot (HDHE) was 2 X 5000 IU heparin with 0.5 mg DHE from Days 1 to 8. There was no difference between the two groups with regard to the tendency to intraoperative bleeding, the incidence of severe wound hematomas and the postoperative hemoglobin course. Blood quantities in the drains were somewhat higher in the Fragmin group. Hemostasis studies showed that, also in patients on Fragmin, the activated partial thromboblastin time, thrombin time and reaction and clot formation time in the thromboelastogram are significantly prolonged three to four hours after injection. The heparin activity measured as the anti-Xa factor was higher by a factor of ten in patients on Fragmin than in those on HDHE. The thromboserate, recorded thermographically with the DeVeTherm unit, was the same in the two groups. Subjective acceptance of Fragmin prophylaxis was distinctly higher. Further studies to establish the required dose and show the effectiveness of low-molecule heparins seem necessary.

Blood Coagulation Tests↗

Coagulation abnormalities in low birth weight infants with peri-intraventricular hemorrhage.

Fifty-four appropriate for gestational age preterm infants (less than 35 weeks gestation) were followed prospectively from birth with coagulation and real-time ultrasound studies. Coagulation analyses included fibrinogen, prothrombin time, thrombin time and platelet count. The occurrence of peri-intraventricular hemorrhage (PIVH) was documented by portable 5 MHz Echo Scanner. Definite PIVH was present in 21 babies (38%). Coagulation studies showed especially lower values of fibrinogen levels in babies of less than 30 weeks gestation compared to a control group without PIVH (p less than 0.03). Furthermore, significant correlation was observed in these patients between platelet count and degree of PIVH. Infants with Grade 3 and 4 PIVH had lower platelet count than infants with less severe bleeding (Grade 1 and 2) (p less than 0.02). These data suggest that hemostatic abnormalities play a major role as co-factor in the incidence and severity of neonatal PIVH in very low birth weight infants of less than 30 weeks gestation.

Blood Coagulation Disorders↗

The Passovoy defect: further characterization of a hereditary hemorrhagic diathesis.

We studied a coagulation abnormality present in 12 members of five kindreds who bruised easily and bled excessively after minor trauma. Their activated partial thromboplastin times were between 32 and 39 seconds (normal, 22.8 to 28.8 seconds). Prothrombin times, thrombin times, platelet-function tests and the levels of factors XII, XI, IX, VIII, prekallikrein and high-molecular-weight kininogen were normal. Within these kindreds inheritance of prolonged partial thromboplastin times followed an autosomal and probably dominant pattern. The prolonged thromboplastin times were corrected by normal plasma and by normal plasma adsorbed with celite, but there was no mutual correction between plasmas of the patients. These subjects shared a common defect in the intrinsic pathway of coagulation that we designate by the proband's surname, Passovoy.

Adolescent↗

Potentially catastrophic bleeding disorders. Approach to diagnosis and management.

Clinical and laboratory evaluation of severe bleeding can detect the presence of an intrinsic or acquired coagulation disorder. The three most common inherited coagulation disorders are factor VIII deficiency (hemophilia A), factor IX deficiency (hemophilia B), and von Willebrand's disease. Vitamin K deficiency, liver disease, and disseminated intravascular coagulation are the most common acquired disorders. A thorough clinical history is crucial to diagnosis. Screening tests that measure prothrombin time, partial thromboplastin time, thrombin time, and platelet count permit initial classification and guide selection of more specific tests. Results can then be used to determine appropriate therapy.

Blood Coagulation Disorders↗

The clinical pathology of Crimean-Congo hemorrhagic fever.

Observations were made of 15 fatal and 35 nonfatal Crimean-Congo hemorrhagic fever (CCHF) infections diagnosed from February 1981 to March 1987 in Kimberly and Sandringham, Republic of South Africa. Following an incubation period of 2-9 days after exposure to infection, patients had a sudden onset of disease with fever, nausea, severe headache, and myalgia. Petechial rash and hemorrhagic signs such as epistaxis, hematemesis, and melena supervened on days 3-6 of illness. Deaths occurred on days 5-14 of illness. Patients with fatal infections had thrombocytopenia and markedly elevated levels of serum aspartate and alanine aminotransaminases, gamma-glutamyltransferase, lactic dehydrogenase, creatine kinase, bilirubin, creatinine, and urea. Total protein, albumin, fibrinogen, and hemoglobin levels were depressed. Values for prothrombin ratio, activated partial thromboplastin time, thrombin time, and fibrin degradation products were grossly elevated, findings that indicate the occurrence of disseminated intravascular coagulopathy. Many of the clinical pathologic changes were evident at an early stage of the disease and had a highly predictive value for fatal outcome of infection. Changes were present but less marked in nonfatal infections.

Animals↗

The effects of Hespan on serum and lymphatic albumin, globulin, and coagulant protein.

The effects of hydroxyethyl starch (Hespan) resuscitation on serum and lymphatic proteins following hemorrhagic shock were studied in 34 splenectomized dogs. Following shock, five randomly assigned treatment groups received the shed blood plus 50 mL/kg of salt solution (RL) or RL with varying concentrations (0.22-1.5 gm/kg) of Hespan. Each dog received 50 ml/kg/d of the test solution for three days after shock. Prothrombin time, partial thromboplastin time, thrombin time, total serum protein, albumin, globulin, and coagulant protein activity of fibrinogen, prothrombin, and factor VIII were measured before shock, at the end of shock, following resuscitation, and on day 3; thoracic duct lymph values were obtained on day 3. Hespan-supplemented resuscitation lowered all serum proteins including albumin, globulin and coagulant proteins; concomitantly, the lymph protein rose after Hespan resuscitation. This decrease in serum proteins and rise in lymph proteins parallels similar results after albumin resuscitation in man and animals and suggests that Hespan induces an oncotically controlled extravascular protein relocation. Further studies on the significance of these findings need to be conducted.

Animals↗

Stability of coagulation proteins in frozen plasma.

This study reports on the frozen stability of all commonly measured coagulation proteins in normal citrated plasma: activated partial thromboplastin time, prothrombin time (%), thrombin time and fibrinogen (Clauss); clotting assays for factors II, V, VII, VIII, IX, X, XI and XII; functional assays for protein C (clotting), protein S (clotting), antithrombin (chromogenic) and plasminogen (chromogenic); and immunological assays for von Willebrand factor and D-dimer. All these factors listed are stable for up to 3 months if frozen at -24 degrees C or lower. At -74 degrees C, all these factors (allowing for 10% variation) were stable for at least 18 months, most were stable for 24 months. The number of proteins showing > 5% variation over baseline after 6 months storage indicates that some decay does occur even at -74 degrees C. There was no clear advantage in snap freezing at -74 degrees C and then storing at -24 degrees C over both freezing and storing at -24 degrees C; therefore, the freezing process itself is not responsible for the loss of stability. The best stability, especially at -24 degrees C, was obtained when small samples (1 ml) were stored in screw-cap tubes with a minimum dead space. The decrease in stability of the coagulation proteins directly correlates with the effect of temperature and time.

Blood Coagulation↗