Disseminated Intravascular Coagulation Syndrome Research Articles

Тромбоцитарные индексы и их прогностическая значимость у больных хроническим гепатитом С

The purpose — to determine the role of platelet count (Tr) and platelet indices — average platelet volume (MPV), platelet distribution width (PDW) in the prognostic significance of the activity of the infectious process in patients with chronic hepatitis C (CHC). Material and methods. 310 CHC patients were under observation. The patients were divided into groups, depending on the number Tr in the phases of disseminated intravascular coagulation (DIC). The first group corresponded to the hypercoagulation phase (Tr > 330 x 109/l, n = 22); the second to the intermediate phase (Tr 330–200 x 109/l, n = 132), the third to hypocoagulation (Tr < 200 x 109/l, n = 91). A group of patients with liver cirrhosis (n = 65), class A (n = 54), class B (n = 11) by Child — Turcotte — Pugh was studied separately. The Tr number and platelet indices PDW and MPV were determined as part of a routine blood test using an automatic analyzer XN-20 (SYSMEX, Japan). Results. The most significant changes in platelet counts were in patients in the phase of hypocoagulation and with liver cirrhosis in comparison with other groups of patients – intermediate phase and hypercoagulation in the form of their growth. In all groups, according to the phases of DIC syndrome, the fibrosis level was lower (p=0.00) compared with patients with liver cirrhosis. Against this background, there was a parallel increase in platelet counts. This confirmed the presence of an inverse correlation between the number of blood plates and the level of liver tissue fibrosis, as well as a direct correlation between the values of platelet parameters: PDW and fibrosis; MPV and fibrosis. An inverse correlation was found between blood platelets and platelet indices PDW and MPV, as well as a direct correlation between PDW and MPV indices. Conclusion. Platelet counts (RDW, MPV) in patients with CHC had an inverse correlation with the number of blood plates and a direct correlation with fibrosis and with each other. The Tr number and platelet indices (RDW, MPV) reflect the activity of the infectious process, which allows using them to predict the course of the disease under the long-term infection with hepatitis C virus.

Markable coagulopathy in the patient with severe COVID-19

The variative coagulation abnormalities with thrombotic and microvascular complications are distinguishing feature of the severe new coronavirus infection (COVID-19) pathogenesis. Abnormal coagulopathy is directly related to the risk of death in COVID-19 patients. In many patients with COVID-19, hemostasis disorders have been observed, which increase the risk of developing DIC (disseminated intravascular coagulation), thrombotic microangiopathy or antiphospholipid syndrome as a result of the pathogenetic factors combination: inflammatory response, endothelial dysfunction, increased platelet consumption, microvascular thrombosis. The mechanism of coagulopathy associated with COVID is still being found, COVID-associated coagulopathy exemplifies the potentiating multi-factor interactions between the immune system and the coagulation. We’re reporting a fatal case of 51-year-old male with COVID-19, complicated by severe acute respiratory syndrome (SARS) and severe thrombocytopenia, markedly enhanced fibrinolytic activity with skin-hemorrhagic syndrome, thrombotic complication (myocardial infarction), probably related to the DIC. This case demonstrates the need more basic and clinical research is warranted to further our understanding of the role of coagulation disorders mechanism in COVID-19 to prevent severe outcomes and mortality.

POST-MORTAL DIAGNOSIS OF DIC SYNDROME FOR ANAPHYLACTIC AND OTHER TYPES OF SHOCK

Diagnosis of terminal conditions is an important field of forensic medicine. When shock occurs all human physiological functions are replaced with pathological processes, including development of disseminated intravascular coagulation (DIC) syndrome, develop. In DIC syndrome two opposite processes, such as increased blood clotting and activation of the fibrinolytic system, take place. This paper provides information on post-mortal diagnosis of DIC syndrome for anaphylactic and other types of shock. The quantitative content of the fibrinogen fraction and the results of paracoagulation tests allow post-mortem diagnosis of DIC syndrome and identification of the process stage. These studies indicate shock at the time of death and are especially relevant for post-mortem diagnosis of anaphylactic and other types of shock.

Clinical and pathophysiological aspects of disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a complex process, the course and outcome of which is determined by triggering mechanisms, the reactivity of the body and a number of related conditions. As a result of these interactions, the clinical and laboratory manifestations of DIC vary greatly, making it difficult to diagnose and correct it. With DIC, there are no standard, especially pathognomonic, clinical symptoms, there are no generally accepted laboratory diagnostic criteria, as well as specific therapy. The development of methods for treating DIC and assessing their effectiveness is hampered by the fact that, firstly, the outcome of DIC depends more on its immediate cause than on treatment; secondly, the usually recommended therapeutic effects (heparin therapy, infusion of antithrombin III concentrates, protein C, etc.) have never been the subject of objective randomized follow-up studies, with the exception, perhaps, of the use of antithrombin III drugs [4]. Undoubtedly, advances in the prevention, diagnosis and treatment of DIC directly depend on the depth of understanding of its pathogenetic mechanisms that unfold at the molecular and cellular levels. Modern ideas about the pathogenesis of DIC syndrome are, in one way or another, a development of the idea of ​​continuous intravascular coagulation [5], which under some conditions from latent physiological becomes massive pathological with distinct clinical and laboratory manifestations [1, 2, 7].

Urinary thrombin as a marker of local disseminated intravascular coagulation in patients with chronic kidney disease

The aim of this research was to study the diagnostic markers of nonovert local disseminated intravascular coagulation (DIC) syndrome in the urine of patients with chronic kidney disease (CKD). We conducted a prospective study involving 140 patients with CKD, of these patients, 100 patients (71.4%; 95% CI 53.4-76.7) had glomerulonephritis (GN) and 40 patients (28.6%; 95% CI 21.3-36.8) had diabetic nephropathy (DN). We diagnosed overt DIC syndrome on the International Society of Thrombosis and Haemostasis (ISTH) scale (>5 points) in 18.6 % of patients. We determined the level of thrombin in the urine of patients who had <5 points on ISTH scale for the diagnosis of local nonovert DIC syndrome in the kidneys. In the urine of healthy individuals, the level of thrombin did not exceed 1 ng/ml, so we found no thrombinuria at a thrombin level <1 ng/ml. In 56.1% of patients, we found urinary thrombin levels >1 ng/ml. The average level of thrombin in the urine of these patients was 6.5 (4.8; 10.6) ng/ml. In our opinion, the presence of thrombinuria indicates the intensity of monocytic-macrophage inflammation in the glomeruli and may be a criterion for nonovert, local DIC syndrome in the kidneys. The association of overt DIC syndrome with decreased blood albumin, reduced glomerular filtration rate (GFR), increased daily protein excretion (DPE) indicates its occurrence in severe underlying disease, in the presence of nephrotic syndrome and in the severe stages of CKD. Early diagnosis of nonovert local DIC syndrome would be more useful, since the process is still reversible and controlled, and timely use of antiplatelet and anticoagulant therapy would affect the course and the progression of CKD.

Splenomegaly development and disseminated intravascular coagulation syndrome in acute canine babesiosis

Disseminated intravascular coagulation (DIC) syndrome is the main defining process in the pathogenetic axis of complications in canine babesiosis. The involvement of the spleen with further irreversible changes in the organ largely determines the severity of the animal’s condition after spontaneous babesiosis. The work presented here aimed to determine the role of the DIC syndrome as a triggering factor for lesions of the spleen. Clinical and laboratory studies (haematological, biochemical, hemodynamic) have been carried out. Pathological studies of the removed spleen were carried out by histological methods using universal and specific staining. After suffering acute spontaneous babesiosis, the development of hypersplenism and splenomegaly was found in dogs. The diagnosis was confirmed haematologically by the detected cytopenia, normochromic type anaemia. An additional parameter was a significantly increased erythrocyte sedimentation rate. The biochemical profile indicated the development of bilirubinaemia due to the conjugated fraction, hyperfermentation of transaminases, hypoalbuminemia, which reflected the development of hepatitis and liver failure. Markers of DIC syndrome in laboratory studies are represented by reliable hypofibrinogenemia, increased level of fibrinogen/fibrin degradation products, including D-dimer, and soluble fibrin monomer complexes. The multidirectional indices of coagulation tests (activated partial thromboplastin and prothrombin time) made it possible to classify the stage of “consumption coagulopathy” of the DIC syndrome. The haemodynamic parameters of the sick dogs were characterized by a significant deficit in the circulating blood volume. Together with the indicators of the “consumption coagulopathy” stage of the DIC syndrome, the hemodynamic indexes indicate a moderate degree of shock stage II – the stable reversibility, but the magnitude of the circulating blood volume deficit determines the tendency towards shock irreversibility. Histological studies have established a significant proliferation of the stromal elements of the organ, the formation of specific complexes of vessels with sinuses, clogging with blood clots, and the organ's parenchyma dystrophy. Such changes characterize complete splenomegaly, which is based on the organo-pathology of the DIC syndrome. The deposition of “old” fibrin in the connective tissue structures of the spleen indicates that DIC syndrome continues throughout the entire period of hyperplastic changes in the organ. The presence of hyalinosis in blood vessel walls of the spleen parenchyma determines irreversible changes in them. Thus, DIC syndrome is the basis for splenomegaly development in dogs after acute spontaneous babesiosis. It is confirmed by laboratory blood tests and histologically by the presence of fibrin thrombi in the structures of the organ, which determine the organopathology of the syndrome. The information obtained serves to expand the concepts of the pathogenesis of blood protozoal disease, define the high risk of complications that can become fatal for the health and life of animals.

Pathogenesis, diagnosis, prevention and treatment of disseminated intravascular coagulation syndrome in COVID-19 infection

Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.

Disseminated Intravascular Coagulation Syndrome as a Complication in Acute Spontaneous Canine Babesiosis

Abstract The polyetiological syndrome of disseminated intravascular coagulation (DIC) is characterized by changes in patients’ hemostasis. The aim of the current research was to elucidate the main factors for the development of DIC syndrome during canine babesiosis, and to assess their correlation level. Dogs included in this study were of various breeds and sex, weighing 10-40 kg and aged 2-7 years. They were separated in two groups (n=50) according to their diagnosis to babesiosis. Oscillometry (blood pressure, pulse rate), vascular-platelet hemostasis, coagulogram, hematological, biochemical (fibrinogen, fibrin degradation product, soluble fibrin-monomer complex) and hemodynamic (circulating blood volume) assessment methods were used. The group of dogs positive on Babesia spp., had clear manifestation of DIC with 5-7% of the erythrocyte population being affected. DIC was manifested by a significant increase in soluble fibrin-monomer complex and fibrin degradation product (p<0.001), hypofibrinogenemia (p<0.001), thrombocytopenia (p<0.001), and an increase in indicators of spontaneous aggregation ability of platelets and red blood cells (p<0.001). Significant hemodynamic disorders were observed: a decrease in circulating blood volume, circulating erythrocytes volume (p<0.05), specific circulating blood volume and hematocrit value (p<0.001). The average blood pressure was reduced (p<0.001), and the Allgöwer’s shock index was increased 2 times (p<0.05). A shock of II degree (medium, subcompensated) was confirmed. Therefore, it can be concluded that acute spontaneous dogs’ babesiosis can be characterized by the occurrence of DIC in a consumption coagulopathy form, and shock of II degree. This condition renders the patients for emergency admission.

Prophylaxis and Treatment Strategy for Endothelial Cell Damages after Hematopoietic Cell Transplantation in Children

Introduction Sinusoidal obstruction syndrome (hSOS) and thrombotic microangiopathy (TMA) are life-threatening complications caused by endothelial cell damage (ECD) associated with hematopoietic cell transplantation (HCT). Danaparoid sodium (DS) is a heparinoid comprising a mixture of low molecular weight glycosaminoglycans with anti-Xa and anti-IIa effects, which prevent fibrin formation. Recombinant thrombomodulin (rTM) comprises the active extracellular domain of thrombomodulin and inactivates coagulation by binding to thrombin. Both of them were expected to play crucial roles in the management of disseminated intravascular coagulation (DIC) and ECD after HCT. Objectives We aimed to evaluate the efficacy and feasibility of DS for prophylaxis and rTM for the treatment of hSOS and TMA after HCT in children. Methods Between January 2011 and December 2017, 91 children (median age 7.6 years, range 0.6–18.2; with hematologic malignancies [n = 54], solid tumors [n = 9], or benign diseases [n = 28]) underwent 118 consecutive HCTs (9 autologous and 109 allogeneic settings; busulfan-based myeloablative conditioning [n = 23], total body irradiation-based myeloablative conditioning [n = 35], or reduced intensity [n = 60]) at our institution. All of them were treated prophylactically with DS (intravenously injection, 30 international units [IU] per kg of body weight, twice a day from the initiation of the conditioning regimen to day 50 after HCT) to prevent ECD. Any patient who developed ECD despite prophylaxis were treated with rTM (intravenous drip infusion, 380 IU per kg, once a day). We reviewed their clinical records and evaluated the efficacy and feasibility of rTM for these children. Results Nine patients developed SOS (severe 5, moderate 1, and mild 3) at a median of 19 days after HCT (range, 6–173), and 6 patients developed TMA at median day 38 (range, 27–106). The cumulative incidences of SOS and TMA at 100 days were 6.8% and 4.4%, respectively. A total of 17 patients received 18 courses of rTM for complications after HCT. The median dose and duration of rTM treatments were 367 IU/kg/day (range, 189–404) and 7 days (range, 3–22), repectively. rTM treatments initiated at a median of 30 days after HCT (range, 6–173). The cause of rTM administration included SOS (n = 9), infection with DIC (n = 4), TMA (n = 3), or engraftment syndrome with DIC (n = 2). All these complications were resolved or improved by rTM treatment along with supportive care. Among the 17 patients receiving rTM treatment, no hemorrhagic events or deaths due to HCT-related toxicity were observed; however, 7 died of their underlying disease. Multivariate analysis revealed that neither SOS nor TMA had a negative impact for transplant outcome. Conclusion DS and rTM are effective and safe for the management of ECD after HCT in children. A larger multicenter prospective study is warranted to confirm these findings.

Modern aspects of the pathogenesis, diagnosis and therapy of hemostasis disorders in children with acute leukemias

Patients with oncohematological diseases, both children and adults, face high risks of thrombotic and hemorrhagic complications.About 40 % of pediatric patients with acute lymphoblastic leukemia develop bleedings, and the incidence of thrombosis in this disease ranges from 1 to 36 %. Most thromboses are associated with the use of central venous catheters and the use of L-asparaginase, which leads to a significant reduction in the synthesis of coagulation proteins.Massive hemorrhages account for two-thirds of all causes of early death in pediatric patients with acute myelogenous leukemia (AML). Absolute risks of death due to bleeding and leukostasis range from 1.8 % in the total population of children with AML to 14.3 % in a population with hyperleukocytosis more than 200 × 109 /l. The risk of thrombotic complications in children with AML varies between 3.4–11 %. In patients with AML, complex systemic coagulopathies may occur, such as disseminated intravascular coagulation (DIC), excessive fibrinolysis, or nonspecific proteolysis. This scale is not yet applicable due to the lack of research on its effectiveness in the pediatric population. The laboratory diagnostics of hemostasis is difficult due to the combined nature of thrombotic and hemorrhagic complications: bleeding, thrombosis and even DIC syndrome (combining both hyper- and hypocoagulation phases) can be expected in each specific patient with hemoblastosis. Because of the long-term nature of the treatment and the varying intensity of the various treatment units, the patient’s hemostasis during disease manifestation does not allow one to predict with any certainty the complications on induction or consolidation therapy. Involving all the components of the hemostasis system – vascular, platelet and plasma – into the pathological process makes prediction and diagnosis of thrombohemorrhagic complications impossible with the help of standard hemostatic tests and a general blood test, since these tests are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostatic system, and does not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests such as thromboelastography, thrombodynamics and thrombin generation test adequately reflect hypercoagulable conditions and can serve as a basis for the development of a new set of laboratory hemostasis tests.Conflict of interest. F.I. Ataullakhanov is co-founder of HemaCore LLC, which holds several patents and patent applications that are related to the diagnostic use of Thrombodynamics® (Ataullakhanov F.I., international patent applications: PCT/CH2007/000543 filing date 02.11.2007 and РСТ/RU2012/000570 filing date 16.07.2012). None of the other authors has any competing interests to declare.

New criteria for sepsis-induced coagulopathy. Review

In 2017 a new criteria for sepsis-induced coagulopathy (SIC) were issued following the revised sepsis definition in 2016. They aimed to the earliest detection of the sepsis-specific thrombotic phenotype of disseminated intravascular coagulation (DIC) in order to improve outcomes with early anticoagulant treatment in critically ill patients with sepsis. The following validation of SIC score demonstrated higher forecast value of that and revealed higher correlation with mortality compared to DIC score by the International Society on Thrombosis and Haemostasis (ISTH). In the future the ISTH plans to offer a simplified two-step scoring system for early DIC syndrome revealing in which SIC scale is as the first step, and the next step is the assessing of overt-DIC in patients who meet the criteria of SIC. The main goal of that should become the opportunity of timely therapeutic effects to the hemocoagulation in order to improve the treatment effectiveness of a sepsis.

Стан системи гемостазу за трансмісивної венеричної саркоми собак

Стан системи гемостазу за трансмісивної венеричної саркоми собак

The evaluation of hemostatic dysfunction and disseminated intravascular coagulation in dairy cows with abomasal displacement.

Disseminated intravascular coagulation (DIC) is a complex, dynamic and hemostatic disorder which develops secondarily to a disease characterized with an imbalance in the pro-coagulant and anti-coagulant components of hemostasis. The aim of the study is to evaluate hemostatic dysfunc- tion and the DIC syndrome in cattle with displaced abomasum (DA), with using the hematologic analyses and an extensive coagulation profile in the 96 hour-period including before and after surgery. The animal material of the study consisted of 12 dairy cows diagnosed with displaced abomasum (9 LDA and 3 RDA without volvulus) in the 2-4 week period after parturation and with no other post-partum disease. In dairy cows diagnosed with DA, hematological, coagulomet- ric (PT, APTT, Fibrinogen) and coagulation factor analyses [D-Dimer, TAT (thrombin-anti- thrombin complex), ATIII (antithrombin III), PAI-1 (plazminogen activator inhibitor-1] were performed in blood samples obtained before the operation as well as 30 minutes, 60 minutes and 2, 5, 10, 24, 48, 72 and 96 hours after the operation. In the DA cases, abnormalities were found in 6 of the 8 coagulation parameters. In the LDA and RDA groups, prolonged PT (sec), PT (INR) and APTT, hypofibrinogenemia, an increase in serum D-Dimer concentration at 72 and 96 hours after the operation and an increase in serum ATIII concentrations before and 30, 60 minutes and 2, 5, 72 and 96 hours after the operation was found (p⟨0.05). Hemostatic dysfunction and the risk of DIC developing in DA cases and continuing in the post-operative period was determined.

Аspects of the methodology of laboratory studies of hemostasis in pediatric hematology-oncology and general approaches in the pathology of hemostasis in leukemia

Children with acute leukemia are faced with high risks of thrombotic and hemorrhagic complications. The pathogenesis of haemostasis disorders in hemoblastoses is complex because, in addition to the disease itself, the aggressiveness of the therapy and the need for numerous invasive manipulations also make a significant contribution. Patients with hemoblastoses are equally susceptible to thrombosis and hemorrhage, which makes it possible to speak of multidirectional shifts in the balance of the hemostatic system in each individual patient. Standard laboratory hemostasis tests (clotting times, marker tests) are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostasis, and in do not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests designed to assess the coagulation balance, such as thromboelastography, thrombin generation test, and thrombodynamics, can be the alternative for the standard coagulation assays. The review focuses on the mechanisms of various laboratory hemostasis tests, as well as an assessment of their informative value in frequent complications of the underlying disease (sepsis leading to the development of disseminated intravascular coagulation (DIC) syndrome, thrombocytopenia) and catheterization, which is present in the majority of patients with hemoblastosis. General screening tests of the blood coagulation system have little diagnostic value in the DIC syndrome in patients with acute leukemia, mainly due to their insensitivity to hypercoagulability. Standard markers (for example, D-dimers) are non-specific and only confirm the clinical manifestations of clotting disorder in sepsis and septic shock, but are unable to predict the dynamics of this process at earlier stages of the inflammatory response. In this case, the thrombin generation test and thrombodynamics make it possible to reveal the hypercoagulable phase of the DIC syndrome. Thrombocytopenia accompanies almost all protocols of chemotherapy. In this case, the degree of bleeding does not always depend only on the concentration of platelets, since chemotherapeutic drugs can affect not only the quantity, but also the functional characteristics of platelets, which are not determined by standard examination of patients. The catheterization that accompanies the treatment of hemoblastoses is the leading cause of thrombosis in children with acute leukemia. Thromboembolism of the pulmonary artery due to thrombosis in the central vein system occurs in 8–15 % of patients. The prediction of catheter-associated thromboses using standard laboratory methods for assessing the state of the hemostasis is not possible. Absence of sensitive tests in modern diagnostic schemes leads to the fact that the attending physician is forced to focus exclusively on the clinical picture of thrombosis or bleeding. The development of new functional methods of hemostasis allows one to think that today the existing standard panel of coagulation tests can be expanded and made much more informative in terms of the prediction of thrombohemorrhagic complications in pediatric hematology-oncology.

English

A male agricultural worker, aged 50 years was admitted with fever of 60 days. He had generalized weakness and headache. He was febrile. Anaemia (haemoglobin 11.7g/dL) and thrombocytopenia (platelet count 80,000/mm3) were evident. He also developed hepatocellular hepatopathy. Other salient laboratory abnormalities included low serum fibrinogen (55 mg/dL), elevated serum creatinine (5.1 mg/dL) suggestive of disseminated intravascular coagulation (DIC). Serum procalcitonin was elevated (15.6 ng/mL). Ultrasonography abdomen showed mild hepatosplenomegaly. Weil-Felix test for scrub typhus was positive in 1:640 dilutions. Serological testing to detect scrub typhus immunoglobulin M antibodies tested positive. During the hospital course of 10 days, he developed pancytopenia (haemoglobin 8.4g/dL, total leucocyte count 3,400/mm3 and platelet count 50,000/mm3), fulminant hepatic failure, acute kidney injury, acute respiratory distress syndrome and DIC. Bone marrow study revealed haemophagocytosis. Patient was managed with intravenous antibodies and supportive management. But the patient died on the 10th day of hospitalization. The patient was diagnosed to have (IgM) scrub typhus with secondary haemophagocytic lymphohistiocytosis complicated by DIC and multiple organ dysfunction syndrome.

Plasmapheresis Is an Effective Approach Preventing Clinically Significant Tumor Lysis Syndrome during Induction Therapy in AML Patients with Hyperleukocytosis

Introduction. Most studies have found that hyperleukocytosis (HL >100*109/l) is a poor prognostic factor in acute myeloid leukemia (AML). It is diagnosed in 5-13 % of cases and is more common in AML with monocytes’ differentiation (M4, M5), as well as in cases with poor prognostic molecular markers, such as FLT3-ITD and others.According to the literature the early (during the first week) mortality in AML due to HL may reach 90%. The main cause of death are leukostasis, leading to neurological symptoms, respiratory distress syndrome (RDS) with lung lesions, disseminated intravascular coagulation (DIC) syndrome with the development life-threatening bleedings and massive tumor lysis syndrome during induction therapy.Aim. National Research Center for Hematology (NRCH) has initiated a prospective clinical study aiming to develop a feasible clinical approach preventing severe tumor lysis syndrome during induction in AML patients with initial WBC >100*109/l by using serial plasmapheresis (PA).Patients and Methods. From Jan 2010 till June 2014, 92 patients with de novo AML were treated in the NRCH according to AML-10 protocol (ClinicalTrials.gov Identifier: NCT01587430). Initial white blood cell (WBC) count more than 100x109/l was detected in 18 patients (19,5%): median age - 38 y (17-56yy), M/F - 10/8, WBC - 130x109/l (100-408x109/l), LDH -1765 µ/l (720-6653). 2 patients were in the favorable, 13 – in the intermediate, 2 - in the poor cytogenetic risk group. 83,3% (15/18) patients had hepatosplenomegaly and lymphadenopathy, 38.8 % (7/18) - gingival hyperplasia, 16,6 % (3/18) - neuroleukemia, 16,6% (3/18) - skin leukemids. All patients had infectious complications at diagnosis.Lung infiltrates due to leukostasis were revealed - in 77,8% (14/18), including 5 patients (27,8%) with RDS; neurological symptoms (headache, blurred consciousness) - in 33,3% (6/18), DIC syndrome - in 8/18 (44,4%) with 1 intracranial hemorrhage.All patients received allopurinole 600 mg/day. PA procedures were started during cytoreductive therapy (hydroxyurea 10 mg/kg/day 1-2 days) sometimes with leukapheresis (LA) and were continued within 1 or 2 days of conventional 7+3 (ARA-C 100 mg/m2 bid iv 1-7 d, DNR 60 mg/m2 x 3d) 2 hours after short (30 min) ARA-C infusion. DNR was applied on days 3 to 5 or 5 to 7, thus PA did not interfere with its pharmacokinetic properties. All patients concomitantly have got intensive hydrating (3-4 l) and diuretic therapy with electrolytes and albumin support.Results: Cytoreductive therapy with hydroxyurea was used for a median 2 days (1-7 dd). Half of the patients (9/18) have got 1-2 procedures of LA (median 2). Median 2 (1-4) procedures of PA were performed in 17/18 patients. The volume of removed plasma for 1 PA procedure was 1200 ml (900-1500 ml), the volume of compensation was – plasma 1100 ml (500-1600 ml) +/- 20% albumin 50-150,0 and 0,9% NaCl 500-1000,0.Median WBC count after cytoreductive therapy at the 1st day of 7+3 was 60x109/l (5,6-124x109/l). DNR was administered on days 5-7 in 16 and on days 3-5 - in 2 patients. No severe cytolysis with the development of multiple organ failure was observed. Only 1 patient with massive extramedullary involvement has developed just laboratory signs of acute renal failure without stopping the urinary function. Less than third of the patients (5/18) developed the transient signs of volemic overload within the first days of chemotherapy treated successfully with diuretics and plasmapheresis.CR after the 1st induction was achieved in 50% of (9/18) patients. Additional 7 patients achieved CR after the 2nd induction, resulting in 89% overall CR rate. Only 1 patient (5,5%) died with severe infectious complications during aplasia. Allogeneic bone marrow transplantation was performed in 8 of 16 CR patients. The median OS and DFS was 28 and 23 months, 3-years OS and DFS was 32% and 35% respectively.Conclusions. Our small study brought us to a conclusion that serial PA procedures during cytoreductive phase and the first days of 7+3 may prevent the development of tumor lysis syndrome and its complications. This clinical approach is feasible, easy to perform and decreases early mortality. DisclosuresNo relevant conflicts of interest to declare.

The specific characteristics of DIC syndrome vary with different clinical settings in the newborn

Two hundred fourteen newborns with serious perinatal pathology (posthypoxic syndrome, sepsis, surgical intervention, etc.) were examined in progress, according to 27 parameters including coagulative, trombocitic, anti-coagulative and fibrinolitic parts of hemostasis system. It was proved, that neonatal disseminated intravascular coagulation (DIC) syndrome had different hemostasiological patterns, which were connected with the genesis: sepsis, surgical intervention or posthypoxic syndrome. Precise periods of DIC syndrome are not always presented in newborns. DIC syndrome with neonatal sepsis has two different patterns (overcompensated and decompensated). The manifestation of trombo-hemorrhagic disorders and their characteristics depend on the genesis of DIC syndrome (e.g. an infection process and hyperbilirubinemia can provide the appearance of hemorrhagic syndrome).

Prostate Cancer Detected During Examination and Diagnosis of Acute Myocardial Infarction and Disseminated Intravascular Coagulation: A Case Report

An 80-year-old male was admitted to our institution with a complaint of chest pain. Electrocardiography revealed ST elevation in leads V1-V5, blood chemistry revealed elevated creatine kinase MB and troponin T levels, and transthoracic echocardiography revealed akinesis in the anterior wall of the left ventricle. Although chest radiography revealed no cardiac or respiratory abnormalities, multiple small nodules in both lungs were identified. A diagnosis of Acute Myocardial Infarction (AMI) was made and Cardioangiography (CAG) was performed, which revealed a severely stenotic lesion in the proximal left descending artery. After thrombectomy, drug-eluting stents were successfully placed. However, intramuscular hemorrhage in the right upper arm and hematuria occurred; moreover, the platelet count decreased to 7.5×104/μL, leading to a suspicion of Disseminated Intravascular Coagulation (DIC). Following treatment of the DIC, the chest nodules detected earlier were investigated further by whole-body computed tomography and magnetic resonance imaging, which revealed a tumor in the prostate gland with metastases to the first lumbar vertebra, ischial bone, and hyoid bone. Prostate cancer was thus detected during examination and diagnosis of AMI and DIC, suggesting an association between the underlying cancer and coagulation disorders such as DIC, venous thromboembolism, and acute coronary syndrome, similar to our patient. This case report suggests that physicians should be mindful of underlying disorders when encountering thrombotic diseases.

Patients with postpartum hemorrhage admitted in intensive care unit: Patient condition, interventions, and outcome

Background:We conducted this study to analyze the data of patients admitted to intensive care unit (ICU) following postpartum hemorrhage (PPH) during one-year period, the interventions they received, and the outcome.Materials and Methods:Case records of patients admitted to ICU with PPH were analyzed. Data retrieved were as follows: Primary admission or referred case, duration between onset of PPH and arrival, condition at admission, resuscitative measures, procedures to manage PPH, presence of disseminated intravascular coagulation (DIC) and its management, duration of ICU stay, and the outcome.Results:Of 21 patients with PPH, 15 were admitted in the ICU. All were referred from other hospitals. Duration between onset of PPH and arrival was 6 (15) hours (mean [standard deviation]). All were conscious on arrival. In 10 patients, blood pressure was not recordable. Tachycardia was a common feature. One patient had bradycardia (54 bpm/BP not recordable). Resuscitative measures included oxygen supplementation and fluid resuscitation. Eight patients underwent uterine artery embolization, 2 patients underwent embolization followed by surgery, and 11 patients underwent surgical intervention only. Twelve patients had DIC on admission which was managed with blood component therapy. Duration of stay in ICU was 12.6 (5.4) days (mean [standard deviation]). Two patients expired following intractable DIC and multiorgan dysfunction syndrome. Though these 2 patients had severe shock on presentation, they did not have DIC at the time of presentation.Conclusions:Despite early resuscitation and intensive care management, DIC is a major cause of mortality. Late onset DIC (onset after admission to ICU) was associated with poor outcome in this study.

Glucocorticoid and cyclosporine refractory adult onset Still’s disease successfully treated with tocilizumab

We report a 29-year-old Japanese woman with disseminated intravascular coagulation (DIC) and adult onset Still's disease (AOSD). Her disease was refractory to high-dose glucocorticoids, two courses of steroid pulse therapy, and addition of cyclosporine (3.5 mg/kg/day). The serum interleukin-6 level was markedly elevated. Therefore, we administered an anti-interleukin-6 receptor antibody (tocilizumab, 8 mg/kg fortnightly), which dramatically improved her symptoms and the levels of acute-phase proteins. In addition, rapid tapering of the glucocorticoid dose was possible. Four months later, she was maintained on tocilizumab infusion once a month with low-dose steroid therapy. Cyclosporine is one of the first-line immunosuppressants for AOSD, especially when associated with DIC, hepatic failure, or hemophagocytic syndrome. In patients with cyclosporine-resistant AOSD, tocilizumab may be another useful option.