Blood Coagulation Disturbances Research Articles

To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries.

Surgical burn excision (along with skin grafting) carries the risk of blood loss. The use of enzymatic debridement agents such as Nexobrid® has gained increased popularity as an alternative to surgical debridement in the management of burns with its reported benefits of selective burn debridement, minimising blood loss and potentially reducing the need for skin grafting. However, there is limited evidence regarding its effects on bleeding. Currently, the manufacturer declares there is no evidence for increased risk of localised bleeding and its systemic effects upon coagulation are less clear. We present two clinical cases demonstrating the possible effects of Nexobrid® on coagulation and bleeding at the debridement site. Comparisons are drawn with the manufacturers' guidance as well as evaluating the current recommendations of its use. Nexobrid® is a novel therapy and there are few adverse effects reported in the literature. The basis of its appeal is the reduced blood loss at the debridement site and the selectivity it possesses in preserving healthy dermis. However, our cases have demonstrated that haemorrhage can occur and that those using Nexobrid® should be mindful of the potential bleeding risk from varicosities within the burn wound. We have also illustrated that Nexobrid® can be used in patients with pre-existing clotting disorders without requiring the use of blood products. However, we emphasise the importance of haematological support for its safe administration. Nexobrid®, a debriding agent that contains enzymes, has been developed as an alternative to surgery which for most surgeons is the traditional method of removing dead tissue following a burn injury. The active agent is bromelain and this is derived from the stems of pineapples. This novel treatment is increasingly being used in the management of middle to deep skin thickness burns and it seems to have a number of benefits such as reducing blood loss, reducing the need for skin grafting as well as being able to treat burns in certain areas of the body that would be technically challenging to remove in the standard fashion. It simply targets the dead tissue leaving viable remnants of the skin that would hopefully allow healing to occur without the need for surgical intervention. Being a relatively new concept, current evidence regarding the safety and value of Nexobrid® continues to develop. In 2020, an agreement guideline outlining best practice with the use of Nexobrid® was published. In this statement, it was advised that caution should be taken when using Nexobrid® in patients who have blood clotting disturbances as this could increase the likelihood of bleeding. However, they did not mention that excessive bleeding can potentially occur with this treatment.We present two clinical cases demonstrating the possible effects of Nexobrid® on the clotting system and bleeding at the application site. Comparisons are drawn with the manufacturers' guidance as well as assessing the current recommendations of its use. We illustrate that Nexobrid® can be safely used in patients with pre-existing clotting disturbances if the correct procedures are performed. We also highlight the potential complication of excessive bleeding if Nexobrid® is used in patients who have co-existing enlarged surface veins along with their burn injury. We feel the guidance should be updated to reflect these findings.

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis.

Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.

Efficacy of CHOP chemotherapy on unspecified peripheral T cell lymphoma in patients aged 80 years and over and its prognostic analysis

Objective To evaluate the efficacy of CHOP(cyclophosphamide, doxorubicin, vincristine, and prednisone)chemotherapy on peripheral T cell lymphomas-unspecified(PTCL-U)in patients aged 80 years and over, and investigate the chemotherapy adverse effects and its prognostic factors. Methods Clinical data of 57 patients with PTCL-U confirmed by pathology and immunohistochemistry in Guangzhou First People's Hospital from January 2008 to January 2015 were retrospectively analyzed. The efficacy and adverse effects of CHOP chemotherapy, and its prognostic factors were evaluated. Results Of 57 patients, 11(19.3%)achieved complete remission, 23(40.4%)had partial remission, 14(24.6%)had stable disease, and 9(15.8%)had progressive disease after CHOP chemotherapy, with a total effective rate of 59.6%(34 cases). The expected 1-year, 2-year and 3-year overall survival(OS)rate was 70.2%(40 cases), 36.8%(21 cases) and 17.5%(10 cases), respectively. The median survival time was 18.2 months. Among the 57 patients, 40(70.2%)had hypoplasia of bone marrow at degreeⅠ-Ⅱ, 17(29.8%)at degree Ⅲ-Ⅳ, 49(86.0%)had mild nausea and vomiting(degreeⅠ-Ⅱ), 8(14.0%)had severe nausea and vomiting(degree Ⅲ-Ⅳ), 7 had liver dysfunction, 2 had cardiac toxicity and 7 had disturbance of blood coagulation. Univariate analysis showed that the alkaline phosphatase, Ki-67 percentage, lymphoma international prognostic index(IPI)score, extranodal involved sites(>1), as well as the efficacy and course of chemotherapy were the prognostic factors for survival time in very elderly patients. Multivariate analysis indicated that IPI score>2(95%CI: 1.12~6.35, χ2=5.45, P 1)(95%CI: 2.58-15.32, χ2=16.42, P 4)(5%CI: 0.18~0.79, χ2=7.28, P<0.01)were the independent prognostic factors for the median survival time in very elderly patients. Conclusions PTCL-U patients aged 80 years and over have poor prognosis. CHOP chemotherapy has a certain effect on PTCL-U in very elderly patients, and chemotherapy side effects can be tolerated. IPI score>2 and extranodal involved sites(>1)are the important prognostic factors in very elderly PTCL-U patients. The completion of full course of chemotherapy with remission occurrence is important to prolong survival time in very elderly PTCL-U patients. Key words: Lymphoma, T-cell, Peripheral; Antineoplastic combined chemotherapy protocols; Elderly, aged over 80 years; Prognosis

PO-22 - Thrombodynamics test for analysis of hemostasis in patients with malignant tumors and predicting thrombotic complications

Close correlation between oncologic diseases and blood coagulation disturbances dictates a necessity of prognosis of the main disease course and contemporary prevention of the thrombotic complications revealed. For this purpose, the global test for the hemostasis system assessment was used to reveal bleeding and thrombogenesis risks - "Thrombodynamics" (TD) allowing analysis in the real time of the thrombogenesis parameters in conditions the most resembling the natural functioning of the blood coagulation system. Parameters of TD test which enable differentiation between hyper-, normo- and hypocoagulation include the speed of the blood clot growth (the time of growth delay, initial and stationary blood clot growth) as well as the physical features of the clot (size and density). The aim of the present study was to access the capability of global hemostasis test Thrombodynamics in the evaluation of risk thrombotic complications in patients with cancer. Prospective investigation of hemostasis parameters was carried out in 23 patients with malignant tumors of the oral cavity, 25 patients with oropharynx cancer of I-II and III-IV stage, 23 patients - with brain metastasis, 21 patients - with glioblastoma aged 42-75 years (mean age 63.8±7.0). Standard coagulation test (activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin (by Quick), international normalized ratio (INR), and fibrinogen concentration are used to estimate hemostasis. The spatial growth of the fibrin clot was estimated in all patients using "Thrombodynamics T-2 Registrator." It was established that TD allowed registration of all types of plasma hypercoagulation manifestations: acceleration of the main clot growth, formation of the spontaneous clots and their different combinations. Sensitivity of international normalized ratio (INR) and thrombodynamics test, while revealing patient group with higher fibrin level, was 43% and 86%, accordingly. Reliable dynamic changes were found for all parameters of TD test during patients follow-up (p<0.05). The results of regression analysis showed that the time of clot growth delay, initial and stationary clot growth speed, and clot size were reliable thrombosis predictors. The study showed that TD test might be effective in revealing oncologic patients with high risk of thrombotic complications and for monitoring of efficiency/safety of the anticoagulant therapy.

Factors affecting the outcome of pulmonary-acute respiratory distress syndrome patients treated with veno-venous extracorporeal membrane oxygenation

To find out the factors affecting the outcome of pulmonary-acute respiratory distress syndrome (pARDS) patients treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO). From November 2009 to April 2014, the clinical data of patients with pARDS supported with VV-ECMO in intensive care unit of China-Japan Friendship Hospital and Chaoyang Hospital were prospectively collected and analyzed. The clinical data included general condition before VV-EMCO, VV-ECMO treatment, ventilator settings of mechanical ventilation and complications during VV-ECMO. All patients were divided into survival group and non-survival group, according to the 28 days' survival situation after VV-ECMO treatment. The clinical data of the two groups before and after VV-ECMO treatment were compared, and the factors affecting outcome of VV-ECMO treatment in the patients with pARDS were analyzed. A total of twenty-five patients were enrolled in the study, of whom 14 patients survived, 11 patients died.The results showed that the proportion of immunocompromised patients with pARDS in the survival group was lower than that of non-survival group (7.1% vs 45.5%, P=0.026). Before the treatment of VV-ECMO, the duration of mechanical ventilation in the survival group was shorter than that in the non-survival group [25(7, 48) vs 48(21, 120) h, P=0.048], and Murray score was also lower than the non-survival group [3.5(3.3, 4.0) vs 4.0(3.9, 4.0), P=0.020]. During the treatment of VV-ECMO, the duration of ECMO support in the survival group was shorter than that in the non-survival group [7.0(5.0, 9.0) vs 13.0(7.8, 26.0) d, P=0.030], and the proportions of disturbance of blood coagulation and circulatory failure in the survival group were lower than those of non-survival group [0% vs 36.4%, 21.4% vs 63.6%, both P<0.05]. In addition, there were five "awake ECMO" patients during the treatment and all in the survival group. The immunocompromised condition, pre-ECMO ventilation duration and Murray score are the important factors influencing the outcome of VV-ECMO treatment in the patients with pARDS.

Identification of concealed disturbance of blood coagulation (deficiency of factor XI) by polymerase chain reaction (experimental study)

Minor bleeding is quite common in children and in some cases masks the serious disease of blood clotting. As a rule, this rare inherited disease associated with deficiency of coagulation factors as the I, II, V, VII, X, XI and XIII, as well as deficiency conjugate, most often, the joint failure factors V and VIII and factor whose synthesis associated with vitamin K. The pediatric clinic is difficult to fulfill a randomized trial because of the difficulty of identifying such children carriers of genetic abnormalities at a specific blood clotting factor. In connection with the model of deficiency of coagulation factor XI in a mammals (Bos Taurus L) with autosomal recessive type of inheritance is particularly promising. Deficiency of coagulation factor XI in cattle is inherited autosomal recessive defect. At the first time this pathology was recognized in Holstein cows in 1969. Frequently the etiologic factor of most hidden genetic defects in animals are point mutations in the coding region of the respective genes. On the contrary it has been found that deficiency of coagulation factor XI cattle (FXID) is a consequence of the insertion of nucleotide sequences within exon 12 of the gene FXI length of 76 base pairs. STOP codon (TAA) was resulted from insertion. Phenotypically deficiency of factor XI (FXID) in calves is resulted in disturbance of blood clotting and characterized by prolonged bleeding from the umbilical cord and anemia. Cows which are heterozygous in deficiency of coagulation factor XI have colostrum pink color. Those animals are frequently suffered from pneumonia, mastitis and endometritis. We monitored the breeding sires and Holstein cows on the carrier of the genetic disease: deficiency of coagulation factor XI. To detect the insertion of nucleotide sequences of 76 bp in size it is recommended to use the polymerase chain reaction.

Specificity of Metabolic Syndrome Model Reproduction at Pubertal and Adult Male Rats

Abstract Background and Aims: Comparative estimation of metabolic syndrome (MS) mediated changes of blood, cardio-vascular system, liver, pancreas and kidneys morphologic structure in adult and pubertal rats. Materials and Methods: Wistar albino male rats of two age categories (young animals of 21 days age (50-70g) and adults (160-180g)) were divided into 4 groups (8 animals in each): 1 - Control 1 (intact young rats); 2 - Control 2 (intact adult rats); 3 - MS3 (young rats with MS) and 4 - MS4 (adult rats with MS). The metabolic syndrome model was induced by full replacement of drinking water with 20% fructose solution (200g/l). After 60 days of MS modeling, determination of rat hematological and serum biochemical parameters, glucose tolerance, blood pressure, liver rates of lipid peroxydation and chromatin DNA fragmentation, as well as morphological macroscopic and microscopic studies were carried out. Results: In pubertal rats, glucose tolerance, hypertension, blood clotting disturbances, DNAfragmentation and lipid peroxydation rates were affected more profoundly, while mature rats showed greater Pseudo Pelger-Huet anomaly development, serum cholesterol and lipoproteins increases, liver and kidney morphology changes. Conclusions: Our current data combined with previous results of other authors allow us to conclude that an animal model (Wistar rats) of MS is quite easily obtained in a full age range, from juvenile to mature rats.

Clinical study on pegaspargase combined with EPOCH regimen in the treatment of relapse and refractory non-Hodgkin's T-cell lymphoma

Objective To observe the effect and toxicity of pegaspargase combined with EPOCH(P-EPOCH)regimen for patients with relapse and refractory non-Hodgkin's' T-cell lymphoma(T-NHL). Methods A total of 15 patients with pathologically diagnosed T-NHL from January 2010 to January 2014 of the Beijing Military Region General Hospital who had been treated with CHOP or CHOP-like regimens were relapse or refractory. They were treated by P-EPOCH regimen [VP16 50 mg/m2, E-ADM 12 mg/m2, VCR 0.4 mg/m2, dissolved in 500 ml saline sustained static drops 24 h on day 1 to 4; CTX 750 mg/m2, intravenous injection on day 5; pegaspargase 2 500 U·m-2·d-1 given as intramuscular injection on day 6; oral prednisone 60 mg/m2 on day l to 6; 21 days of a cycle]. Results All the 15 patients were treated by P-EPOCH regimen. The response rate of the whole group was 66.7 %, including CR 4 cases(26.7 %)and PR 6 cases(40.0 %). The median survival time was 20 months(5-30 months), and(2-year)overall survival rate was 46.6 %. Main side effects were myelosuppression, liver dysfunction and disturbance of blood coagulation. Conclusion P-EPOCH regimen is effective for patients with relapse and refractory T-NHL and has better tolerance, and wovthy of clinical study. Key words: Pegaspargase; EPOCH regimen; Non-Hodgkin's T-cell lymphoma; Treatment outcome

Preventative effects of caffeic Acid phenyl ester on cadmium intoxication induced hematological and blood coagulation disturbances and hepatorenal damage in rats.

The preventative effect of caffeic acid phenyl ester (CAPE) against hematological, blood coagulation, and hepatorenal disturbances in cadmium (Cd) intoxication was investigated in rats. Male Wistar rats were randomly assigned into control group, Cd-group, and Cd + CAPE group. Cd intoxication was induced by intraperitoneal injection (i.p.) of CdCl2 (1 mg/kg/day) for 21 days, and CAPE was daily given (10 micromol/kg; i.p.) for also 21 days. The results showed that Cd intoxication impaired hepatorenal function and significantly prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen level, red blood cells and platelets counts, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Interestingly, all these hematological, blood coagulation, and hepatorenal deteriorations of Cd toxicity were significantly prevented by CAPE. Additionally, CAPE significantly reversed the significant decreases in levels of total reduced glutathione and superoxide dismutase and increases in levels of thiobarbituric acid reactive substances that were observed in the sera and liver and kidney homogenates of Cd group. It is concluded that CAPE is a promising compound that can counteract the hematological and blood coagulation disturbances, oxidative stress, and hepatorenal damages in Cd intoxication. However, further studies are crucially needed to improve this treatment in patients.

Biochemical and biological characterization of two serine proteinases from Colombian Crotalus durissus cumanensis snake venom

Two clotting serine proteinases, named Cdc SI and Cdc SII, were isolated and characterized for the first time from Colombian Crotalus durissus cumanensis snake venom. The enzymes were purified using two chromatographic steps: molecular exclusion on Sephacryl S-200 and RP-HPLC on C8 Column. The molecular masses of the proteins, determined by MALDI-TOF mass spectrometry, were 28,561.4 and 28,799.2 Da for Cdc SI and Cdc SII, respectively. The aim of the present study was to evaluate enzymatic, coagulant and toxic properties of the two enzymes. The serine proteinases hydrolyzed specific chromogenic substrate (BaPNA) and exhibited a Michaelis–Menten behavior. Cdc SI had Vmax of 0.038 ± 0.003 nmol/min and KM of 0.034 ± 0.017 mM, while Cdc SII displayed values of Vmax of 0.267 ± 0.011 nmol/min and KM of 0.145 ± 0.023 mM. N-terminal sequences were VIGGDEXNIN and VIGGDICNINEHNFLVALYE for Cdc SI and Cdc SII, respectively. Molecular masses, N-terminal sequences, inhibition assays, and enzymatic profile suggest that Cdc SI and Cdc SII belong to the family of snake venom thrombin-like enzymes. These serine proteinases differed in their clotting activity on human plasma, showing a minimum coagulant dose of 25 μg and 0.571 μg for Cdc SI and Cdc SII, respectively. Enzymes also showed coagulant activity on bovine fibrinogen and degraded chain α of this protein. Toxins lack hemorrhagic and myotoxic activities, but are capable to induce defibrin(ogen)ation, moderate edema, and an increase in vascular permeability. These serine proteinases may contribute indirectly to the local hemorrhage induced by metalloproteinases, by causing blood clotting disturbances, and might also contribute to cardiovascular alterations characteristic of patients envenomed by C. d. cumanensis in Colombia.

Monocytic Ehrlichiosis in dogs

Ehrlichiosis is the multiorgan infectious disease caused by small, intracellular rickettsias from the genus Ehrlichia. These microorganisms are known as an etiologic factor of infections world wide in humans and in different species of animals. Dog ehrlichiosis can be caused by several species of Ehrlichia attacking different groups of blood cells, but most often an infection by Ehrlichia canis is diagnosed with special relation to monocytes. A vector for E. canis are Rhipicephalus sanguineus and Ixodes ricinus, commonly occurring in Poland. Disease caused by E. canis is known as Canine Monocytic Ehrlichiosis (CME). The disease most often has an asymptomatic course which can, in favourable circumstances, run into acute or chronic forms. The acute form of CME proceeds usually with fever, apathy, weakness and accompanying respiratory symptoms, lameness and disturbances in blood coagulation. In laboratory examinations thrombocytopenia, anemia and leucopenia are ascertained. The chronic form of CME proceeds among gentle, unspecific symptoms which may last even 5 years. The CME diagnosis is difficult and often demands parallel different diagnostic methods. A medicines of choice in the ehrlichiosis treatment are antibiotics from the group of tetracyclines, given at least for 28 days. They are largely efficient during treatment of the acute CME, causing the quick improvement. Instead, in the case of chronic form, answer for treatment can be weak, and cases of resistance to antibiotics ave known.

Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure

Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

Lonomia obliqua caterpillar envenomation causes platelet hypoaggregation and blood incoagulability in rats

Envenomation caused by Lonomia obliqua is a public health hazard in Southern Brazil. Envenomed victims present severe hemorrhagic syndrome that can progress to intracranial hemorrhage and death. To understand the mechanisms that lead to hemorrhage, we investigated the platelet dysfunction and blood coagulation disturbances following experimental envenomation in rats. L. obliqua bristle extract was injected (s.c.) and blood collected at different times post-venom administration for determination of platelet response and analysis of blood coagulation. Rats presented hypofibrinogenemia and platelet hypoaggregation in platelet rich plasma (PRP). After addition of exogenous fibrinogen to PRP, platelet hypoaggregation was not corrected. Interestingly, normoaggregation was observed when platelets were separated from plasma. In addition, incubation of plasma from envenomed rats inhibits aggregation response of normal washed platelets. These results indicate that an aggregation inhibitor is generated in plasma during envenomation. Moreover, rats presented an increase in nitric oxide plasmatic levels which coincided with maximum inhibition in platelet aggregation. Animals also showed blood incoagulability and a significant increase in thrombin, plasmin and urokinase plasmatic activities. Despite this intravascular thrombin generation, only a slight decrease in platelet numbers was detected. Certainly, the platelet hypoaggregation and blood incoagulability described herein contribute to systemic bleeding observed in patients.

High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study

Reports have been published on blood coagulation disturbances by valproate therapy. In the present prospective trial, blood samples were drawn before valproate therapy, after 6 weeks of therapy, after more than 6 weeks and after longer than 6 months of valproate therapy from 23 children newly treated with valproate. Two children developed thrombocytopenia, and six children with initial normal von Willebrand factor showed acquired von Willebrand's disease. Fibrinogen levels dropped below the lower limit in 12 patients and subnormal factor XIII plasma levels were observed in 17% of patients. No patient developed signs of hemorrhage. Eight percent of patients developed valproate-induced thrombocytopenia. Reduction in platelets did not reach statistic significance. Thrombelastography showed a 47% incidence of altered platelet function. We found a statistically significant, positive correlation between clotting time of collagen extrinsic pathway inhibitor and, accordingly, adenosindiphosphate and valproate level. Plasmatic coagulation investigations showed a significant decrease of prothrombin time. Activated partial thromboplastin time measurements also showed significant prolongation with valproate. Activity of von Willebrand factor antigen and von Willebrand factor ristocetin cofactor significantly decreased. Factor XIII activity significantly decreased after valproate therapy for longer than 6 months (17% of children). Fibrinogen was significantly reduced. In the coagulatory system a decrease in the main antiprotease antithrombin III activity was observed. Blood coagulation disturbances are common in patients with valproate, but rarely become clinically symptomatic. Acquired von Willebrand's disease and hypofibrinogenemia may become relevant in patients with surgery or trauma. Particular attention should be paid to factor-XIII deficiency, which is especially seen with valproate therapy.

Peritoneovenous shunt in ascites therapy. Complications and their treatment

Complications occurred in 29 of 37 patients after ascites retransfusion (n = 16) or introduction of a peritoneovenous shunt (n = 21). Blood clotting disturbances, that could either be successfully treated with drugs or which led to interruption of the reinfusion, appeared in 38%. Estimation of plasminogen proved to be of reliable prognostic value thus enabling prophylactic measures to be taken. Post-operatively 14 patients had transient fever not requiring specific treatment. Local fibrinolysis or shunt revision was successful in three patients with shunt thromboses. According to our experience most complications can be avoided by prophylactic and therapeutic measures.

Fatal complications of tropical malaria in non-immune patients. A retrospective clinico-pathologic analysis of 25 cases

Clinical and pathological data on 25 fatal cases of tropical malaria were obtained from several hospitals in a retrospective survey. The patients originated, without exception, from non-malaria endemic regions (non-immunes). Death occurred in nine patients despite elimination of the parasitaemia with schizontocides. Life threatening complications were complex and apparently interacting. Manifestations of the disease included (1) initial acute renal failure, (2) disturbance of water and electrolyte balance, (3) cerebral oedema resulting in microhaemorrhages, (4) lung oedema, and increasing respiratory insufficiency even after elimination of the parasitaemia (in 4 cases there was histological evidence of shock lung), (5) myocarditis (histological evidence of cellular myocardial infiltration obtained in 4 cases), (6) hepatocellular damage, (7) complications associated with intensive-care treatment in 2 cases. The data allow no conclusions on the intensity and nature of blood clotting disturbances. According to this analysis the clinical manifestations of advanced malaria resemble protracted shock conditions having other aetiologies. However, specific cerebral and cardiac complications and homeostatic disturbances do apparently occur, the treatment of which requires experience with the clinical syndrome.

Role of Zinc in Hemostasis: A Review

Zinc is a multi-functional element that is found in almost 300 enzymes where it performs catalytic, co-catalytic, and/or structural functions. In 1982, Gordon et al. (Am J Clin Ntr 35:849-857, 1982) found that a low zinc diet caused poor platelet aggregation and increased bleeding tendency in adult males. This fact drew interest to the role of zinc in blood clotting. It has been shown that hyperzincemia predisposes to increased coagulability, and hypozincemia to poor platelet aggregation and increased bleeding time. The blood clotting disturbances can be regressed by appropriate zinc intake management. Considering the importance of zinc as an essential element, its participation in regulation of the equilibrium between pro- and anti-thrombotic factors originating in platelets and endothelium prompted further investigations.

Transperitoneal laparoscopic radical nephrectomy

Background: Our purpose was to present our experiences with transperitoneal laparoscopic radical nephrectomy in patients with renal cancer and to compare our results with those published in the literature. Patients and methods: Between June 2000 and March 2006 in 11 patients with age range 39 to 82 years (mean 56.3 years) in whom the renal cancer was found, we tried to do transperitoneal laparoscopic radical nephrectomy. For diagnosis of renal cancer abdominal ultrasound, CT scan, chest X-ray, blood and urine tests were done. During operative procedures we measured the operating time and blood loss. After procedure we registered analgesics needs of patients, hospital stay and patient’s return to normal activity. In all cases pathological examination of the specimen was done. Results: Laparoscopic procedure was performed entirely in 8 patients. We have to reoperate 1 patient on second day after the first procedure because of the bleeding caused by blood coagulation disturbances. In 3 patients conversion into classical technique was necessary (major bleeding or technical difficulties). In 2 patients among 8 cases we finished the laparoscopic procedure using the hand-assisted technique. All patients had a renal cell carcinoma, 4 patients (50 %) in stage pT1, 2 (25 %) in stage pT2 and 2 (25 %) in stage pT3. The mean operating time was 209 minutes. Two patients were transfused with packed red cells. Analgesics were in all patients necessary on the day of operating procedure and the day after. The postoperative hospitalization range was 4 to 7 days. The patients began with normal physical activity 5 to 15 day after surgery. Conclusions: Our initial results with transperitoneal laparoscopic radical nephrectomy are comparable with those published in the literature. We believe that use of proper vascular staplers, other needful instruments and more experiences can significantly reduce the operating time.

Febres hemorrágicas por vírus no Brasil

To call attention to viral hemorrhagic fevers, diseases that are mostly underdivulged and, probably, underreported, we present here case reports of the 4 diseases of this kind that occur in Brazil: yellow fever, dengue haemorrhagic fever/dengue shock syndrome, arenavirus haemorrhagic fever and hantavirus cardiopulmonary syndrome. Relevant clinical, epidemiological and laboratorial diagnostic aspects of these viral haemorrhagic fevers are also shown here. These diseases have a high case fatality rate, induce capillary leaking and blood coagulation disturbances that are evidenced by hemoconcentration and thrombocytopenia. An early clinical diagnosis and treatment is fundamental for patient survival.

Anticoagulant and antifibrinogenolytic properties of the aqueous extract from Bauhinia forficata against snake venoms

The aqueous extract from aerial parts of Bauhinia forficata was able to neutralize the clotting activity induced by Bothrops and Crotalus crude venoms. The clotting time, upon human plasma, induced by B. moojeni venom was significantly prolonged. Clotting and fibrinogenolytic activities induced by isolated thrombin-like enzyme from Bothrops jararacussu were totally inhibited after incubation at different ratios. The extract was not able to neutralize the hemorrhagic activity induced by an Bothrops venoms, but it efficiently inhibited the edema induced by Crotalus durissus terrificus venom and isolated PLA 2s. In addition, it did not inhibited the phospholipase A 2 activity of Bothrops snake venoms. Interaction studies between Bauhinia forficata extract and snake venoms, when analyzed by SDS-PAGE, did not reveal any apparent degradation of the venom proteins. This extract is a promising source of natural inhibitors of serine-proteases involved in blood clotting disturbances induced by snake venoms.