Splenectomy for Visceral Leishmaniasis Out of an Endemic Region: A Case Report and Literature Review.

Visceral leishmaniasis (also known as kala-azar) is characterized by fever, weight loss, swelling of the spleen and liver, and pancytopenia. If it is not treated, the fatality rate in developing countries can be as high as 100% within 2 years. In a high risk situation for perioperative bleeding due to severe thrombocytopenia/coagulopathy, we present a rare challenge for urgent splenectomy in a patient with previously undiagnosed visceral leishmaniasis. A histologic examination of the spleen revealed a visceral leishmaniasis, and the patient was successfully treated with amphotericin B.

Comparison of standard fibrinogen measurement methods with fibrin clot firmness assessed by thromboelastometry in patients with cirrhosis.

BACKGROUND: The Clauss fibrinogen method and thrombin clotting time (TCT) are still routinely used in patients with cirrhosis to define fibrinogen concentration and clotting potential. The thromboelastometric functional fibrinogen FIBTEM assay evaluates the strength of fibrin-based clots in whole blood, providing information on both quantitative deficit and fibrin polymerization disorders. OBJECTIVE: To compare these three methods of assessing fibrinogen in patients with cirrhosis of different aetiologies, characterized by impairment in fibrinogen concentration as well as functional aberrance. METHODS: Sixty patients with alcoholic and 24 patients with cholestatic cirrhosis were included (Child-Pugh score (CPs)A, n=24; B, n=32; C, n=28). All parameters were compared with those from a control group. Maximum clot firmness (MCF) in the FIBTEM test was assessed in regard to its relevance in detection of qualitative fibrinogen disorders in comparison with results obtained by standard measurement methods, i.e. the Clauss fibrinogen method and TCT. RESULTS: With increased cirrhosis severity, fibrinogen and FIBTEM-MCF levels significantly declined (p=0.002), while TCT was significantly prolonged (p=0.002). In all CPs groups, fibrinogen strongly correlated with FIBTEM-MCF (r=0.77, r=0.72, r=0.74; p<0.001), while cross-correlations of other assays were highly variable. The prevalence of decreased FIBTEM-MCF values (<9 mm) was significantly higher in advanced CPs categories (p=0.027), whereby the highest prevalence was detected in patients with CPsC (10/16; 62.5%). Nine of the 16 patients with decreased FIBTEM-MCF values had also decreased fibrinogen levels, while in the remaining 7 patients fibrinogen levels were within the reference range, indicating the possible presence of qualitatively altered fibrinogen that could be detected by FIBTEM-MCF. CONCLUSIONS: FIBTEM-MCF may be considered as a reliable alternative to standard plasma fibrinogen measurement in cirrhotic patients, especially in evaluating fibrin polymerization disorders in these patients. Further studies are needed to evaluate the usefulness of this assay in predicting bleeding complications in cirrhotic patients as well as monitoring replacement treatment.

Diagnostic relevance of ADAMTS13 activity: evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis.

INTRODUCTION: The significance of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif-13) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) is still a controversial issue. OBJECTIVE: The aim of this report was to analyze the value of ADAMTS13 measurements in the diagnosis of TTP and HUS. METHODS: At presentation, we analyzed patients with idiopathic TTP (n = 18), secondary TTP (n = 4), diarrhea positive HUS (n = 3) and diarrhea negative HUS (n = 3) treated in Belgrade, Serbia from 2004 to 2010. ADAMTS13 activity from acute phase samples was measured using the residual collagen binding activity assay at the Haemophilia and Thrombosis Centre, Milan, Italy. RESULTS: There was a significant correlation between reduced ADAMTS13 activity and idiopathic TTP diagnosis (p = 0.000) as well as between lower ADAMTS13 activities and higher reticulocytes (p = 0.017) and lactate dehydrogenase levels (p = 0.027). Significant correlation was also found between higher protease activity and diagnosis of HUS (p = 0.000). There was a statistically significant correlation between higher ADAMTS13 activities and higher platelets count (p = 0.002), blood urea nitrogen (p = 0.000), and creatinine level (p = 0.000). CONCLUSION: Severe ADAMTS13 deficiency points at the diagnosis of idiopathic TTP and it is present in the secondary TTP but not in HUS.

PFA-100 test in the detection of platelet dysfunction and monitoring DDAVP in a patient with liver cirrhosis undergoing inguinal hernia repair.

INTRODUCTION: Hemostatic abnormalities in liver cirrhosis are complex and multifactorial and may predispose to prolonged hemorrhage following invasive procedures. Due to increased perioperative bleeding risks, patients with cirrhosis should undergo elective surgery after making medical preparations. It has been shown that 1-deamino-8-D-arginine vasopressin (DDAVP), desmopressin, can be used as a safe and effective remedy in preventing and treating bleeding in cirrhotics. However, there is still scarce information of adequate test(s) for assessing effects of DDAVP in platelet dysfunction. The use of platelet function analyzer-100 (PFA-100) allows more reliable assessment of impaired primary hemostasis as well as follow-up of hemostatic changes induced by DDAVP effects. CASE OUTLINE: In a 49-year-old male with ethylic liver cirrhosis and prolonged bleeding time scheduled for elective left side inguinal hernia repair, we carried out PFA-100 testing to investigate the patients platelet functional status. Results were affirmative for the presence of platelet functional problems. By standard coagulation tests the patient was also identified as having secondary hemostasis. Preoperatively, PFA-100 was used to test the patient's response to a standard dose of DDAVP, which was favorable. The patient was operated after medical preparations with DDAVP and vitamin K. Neither bleeding complications nor side effects of DDAVP were recorded in the perioperative period. CONCLUSION: The PFA-100 is a simple and reliable test for the assessment of primary hemostasis as well as in monitoring of DDAVP therapy.

Heparin-induced thrombocytopenia with iliacofemoropopliteal thrombosis in a patient operated for colorectal carcinoma liver metastases.

We report a case of heparin-induced thrombocytopenia thrombosis (HITT) syndrome in a patient prophylactically treated with low molecular weight heparin. A 66-year-old men underwent radiofrequency-assisted partial liver resection for colorectal carcinoma liver metastases a year-and-a-half after he had been operated for rectal cancer. In the postoperative period, patient was prophilactically treated with reviparin sodium. On the 8th postoperative day, the platelet count decreased by more than 50% without clinical signs of thrombosis. HITT syndrome was suspected on the 19th postoperative day, after iliacofemoropopliteal thrombosis had developed, and related diagnosis was supported by the strongly positive particle gel agglutination technique immunoassay. Heparin was withdrawn and alternative anticoagulant, danaparoid sodium, was introduced in therapeutic doses. Despite delayed recognition, favorable clinical outcome was achieved. HITT syndrome should be considered with priority among the possible causes of thrombocytopenia in a surgical patient on heparin.

Bloodless esophageal replacement in children with corrosive esophageal strictures--report of two cases.

BACKGROUND: Esophageal replacement is major procedure with high risk for perioperative allogeneic blood transfusion (ABT), especially in pediatric patients due to nutritive deficiency, anemia, small body weight and blood volume. Autologous blood policy is particularly important in female children. METHODS: We present treatment strategy with the aim of avoiding ABT, that have been applied in two female pediatric patients with caustic stricture of thoracic esophagus. The patients were 7 and 8 years old, with body weight 34 and 23.5 kg, respectively. Protocol was based on the stimulation of haematopoetic system with erythropoietin, iron therapy and preoperative autologous blood donation (PABD). In the first patient, with a history of previous retrosternal bypass esophagocoloplasty and extraction of necrotic colonic graft, delayed reconstruction--transhiatal subtotal esophagectomy and gastric pull-up with cervical anastomosis were performed. In the second patient, repeated ineffective dilatations of esophageal stricture were reason for retrosternal left colon interposiotion and exclusion of native esophagus. RESULTS: No adverse events were attributed to preoperative blood donation period. No allogenic blood products were used during perioperative period. Both patients had uneventful postoperative course. CONCLUSION: In specialized institutions for esophageal surgery, PABD with administration of erythropoietin and iron therapy, enable bloodless esophageal replacement, even in children.

Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura.

The clinical course of thrombotic thrombocytopenic purpura (TTP) is characterized by recurrent disease episodes in up to 50% of cases. The clinical presentation and severity of different TTP episodes have not been systematically compared. Laboratory and clinical information from 51 patients with recurrent disease, derived from 136 patients with TTP included in the Milan TTP registry (URL: http://www.ttpdatabase.org), were used to compare mortality, symptoms and disease-related laboratory measurements in different disease episodes. The prevalence of severe neurological symptoms (coma, seizures, and focal neurological defects) was significantly lower in recurrences than in the first episode. Platelet counts and haemoglobin levels at presentation were higher in recurrences than in the first disease episode, and lactate dehydrogenase levels were lower. Also, mortality tended to be lower in the second and third disease episodes than in the first. Recurrences of TTP are generally milder than first episodes. These differences in severity should be taken into account in clinical research on TTP and in patient management.

The role of rotational thromboelastometry in real time assessment of haemostasis in surgical settings.

INTRODUCTION: In the settings of trauma, liver transplantation and major surgery multifactorial coagulopathies are frequently encountered. The treatment of acutely bleeding patients is critically compromised by monitoring with standard available routine coagulation tests. In contrast to conventional tests, rotational thromboelastometry (ROTEM) provides an automated measurement of interactive dynamic haemostatic processes in whole blood starting with initial haemostasis up to and including fibrinolysis at a given time point. Especially fibrinogen, platelet dysfunction and hyperfibrinolysis pose diagnostic gaps. The aim of this report was to highlight the usefulness of ROTEM in making the correct diagnosis and adoption of therapeutic approaches in a timely manner in liver transplantation and trauma. We describe the value of ROTEM in two haemostatically compromised patients. OUTLINE OF CASES: In the first case, we present the ROTEM-based dynamic assessment and goal-directed treatment of acute haemorrhage in a liver transplant recipient. In the second case, after operation a multitraumatised patient developed uncontrolled massive bleeding unresponsive to conventional treatment and recombinant activated factor VII (rFVIIa) administration. The cessation of bleeding was achieved after guided therapy according to ROTEM results. CONCLUSION: In orthotopic liver transplantation and severely injured trauma patients ROTEM enables rapid and accurate detection and the differential diagnosis of multifactorial coagulopathies. Also, it provides the basis of rational approach to the use of blood component therapy and pharmacological interventions.

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

[The use of recombinant activated factor VII to control haemorrhage following exenteration and massive transfusion in coagulopathic patients].

INTRODUCTION: Exentheresis pelvis totalis due to locally advanced pelvic malignancies is an extensive surgical procedure. The operation is commonly associated with anticipated perioperative haemorrhage requiring a large volume of haemoproducts. Sometimes, the intervention can result in unexpected massive and uncontrolled haemorrhage that is frequently a combination of surgical and coagulopathic bleeding. Attempts to arrest massive bleeding by conventional means may fail. CASES OUTLINE: We describe our experience in the use of recombinant activated factor VII (rFVIIa) in three previously hemostatically competent patients who underwent exentheresis in order to control massive bleeding resulting from dilution coagulopathy in the operating theatre, as well as in the treatment of postoperative bleeding associated with consumptive coagulopathy. Of these, two massively transfused patients developed dilution coagulopathy in the operative theatre, which was poorly responsive to conventional management. In both cases, a single dose of rFVIIa (70 microg/kg and 60 microg/kg respectively) was given. Prompt clinical response was achieved and operations were successfully finished. In the third case, the patient developed consumptive coagulopathy on the first day after surgical procedure that was treated with conventional therapy. On the second postoperative day the patient became anuric and experienced severe intraabdominal bleeding. The bleeding was successfully controlled with rFVIIa in a single dose of 70 microg/kg. CONCLUSION: RFVIIa can be a treatment option in patients suffering from intractable coagulopathic bleeding when standard therapy has failed.

[The use of recombinant activated factor VII in the treatment of gastrointestinal bleeding following acetylsalicylic acid therapy in a surgical patient].

INTRODUCTION: Gastrointestinal bleeding is the most important complication associated with acetylsalicylic acid therapy. Patients with preexisting haemostatic disorders are at the higher risk and may experience life-threatening hemorrhagic syndrome. Platelet transfusions and desmopressin administration commonly successfully arrest bleeding. However, in clinical situations with profound bleeding and haemorrhagic shock, these therapeutic approaches may fail. CASE OUTLINE: We report a 24-year old female patient with previously undetected acquired platelet dysfunction, who underwent reconstructive surgical intervention. On the 20th postoperative day, acetylsalicylic acid was introduced due to reactive thrombocytosis (platelet count 1480x10(9)/L) with daily dose of 100 mg tablets. On the 12th day of the acetylsalicylic acid treatment, massive gastrointestinal bleeding with haemorrhagic shock suddenly occurred. Attempts to control massive haemorrhage by resuscitation, blood products and haemostatics (desmopressin, tranexamic acid) failed. Two bolus doses of recombinant activated factor VII (rFVIIa) (100 microg/kg and 60 microg/kg respectively) in 90 minutes interval were given. Bleeding was successfully controlled with no requirements for further haemoproducts and haemostatic remedies treatment. CONCLUSION: This case demonstrates that the use of rFVIIa may be a specific treatment option in patients suffering from severe gastrointestinal bleeding associated with acetylsalicylic acid treatment.

[Treatment of 36 cases of thrombotic thrombocytopenic purpura]. / Rezultati lecenja trombozne trombocitopenijske purpure na 36 bolesnika.

Thirty-six patients (pts.) with thrombotic thrombocytopenic purpura (TTP) were treated between May 1990 and May 2003. There were 31 women and 5 men; the average age was 37 years. Twenty-five cases were idiopathic and 11 secondary (3 infection--related, 5 occurred during pregnancy and 3 were drug--associated). The mean lag period between the first symptoms and the diagnosis was 8.5 days (in 14 pts. < or = 5; in 22 > 5). On diagnosis neurological symptoms were present in 31, bleeding in 33, fever in 21 and renal impairment in 27 patients. The mean hemoglobin was 67.5 g/L, the mean platelet count was 10 x 10(9)/L, and the mean reticulocytosis was 17%. The mean serum LDH was 1457 IU. Treatment included plasma exchange (PE) in 24 pts. and only plasma infusions in 12 pts. There were 24 complete responders (20 on PE) and 12 deaths (4 on PE); PE significantly improved survival (p < 0.01). There were 5 treatment-related complications due to the infection and bleeding, 17 exacerbations and 4 relapses. The mean time delay before the onset of symptoms and the treatment initiation lasted for 9 days suggesting the poor disease recognition; the mean time delay from diagnosis to PE institution was 6 days, indicating postponed PE. The mean treatment duration in all patients was 18 days; the mean number of PE cycles needed for the platelet count stabilization was 9. Good prognostic indicators of survival were: the longer prodromal period (> 5 days), the secondary form of TTP and the absence of coma at presentation. The use of PE significantly improved survival. TTP is a severe disorder requiring early recognition and diagnosis in general medical care facilities, which should lead to the timely treatment with PE.