Low-dose heparin in the management of acute myelocytic leukaemia.

The effectiveness of heparin in acute leukaemia complicated by disseminated intravascular coagulation (DIC) is still controversial. In this regard low-dose heparin was found to be therapeutically effective in three patients suffering from acute myelocytic leukaemia and DIC. With respect to the contraindication of high-dose heparin in these conditions the low dose regimen appears to be a valuable alternative.     

弥漫性血管内凝血产妇围术期凝血与纤溶系统指标的检测及临床意义

目的:探讨弥漫性血管内凝血(DIC)产妇围术期凝血与纤溶系统指标检测的临床意义。方法:选择2017年1到2017年12月在我院接受治疗的DIC孕妇57例(DIC组)为研究对象,采取分层抽样的方法选择同期在我院进行产检的正常孕妇57例(健康孕妇组)及在我院体检的健康非孕妇57例(非孕妇组)作为对照,比较各组凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、D-二聚体(D-D)及血小板计数(PLT)变化,根据DIC组的治疗结果分为有效组和无效组,并比较两亚组治疗前PT、TT、APTT、FIB、D-D、PLT,采用Pearson相关分析法分析DIC组治疗前各检测指标间的相关性。结果:与健康孕妇组、非孕妇组比较,DIC组PT、TT、APTT延长(P0.05),D-D水平升高(P0.05),FIB、PLT水平降低(P0.05);与非孕妇组比较,健康孕妇组PT、TT、APTT缩短(P0.05),D-D水平降低(P0.05),FIB、PLT水平升高(P0.05)。DIC组患者治疗后有效组治疗前的PT、TT、APTT短于无效组(P0.05),D-D水平低于无效组(P0.05);FIB、PLT水平高于无效组(P0.05)。Pearson相关分析结果显示,除PT与APTT之间无明显相关性(P0.05)外,其他凝血、纤溶系统指标之间均存在一定的相关性(P0.05)。结论:DIC孕妇围术期凝血与纤溶系统指标异常改变,检测凝血与纤溶系统指标对DIC孕妇的诊疗具有重要意义。     

Disseminated intravascular coagulation in acute monoblastic leukemia: response to heparin therapy.

A 27-year-old man with acute monoblastic leukemia had clinical and laboratory evidence of disseminated intravascular coagulation (DIC), which was exacerbated by induction chemotherapy. Heparin therapy, adjusted according to the patient''s clinical status and the results of coagulation studies, rapidly controlled the manifestations of DIC.     

Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure, mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case

Disseminated intravascular coagulopathy (DIC) is characterized as activation of the clotting system resulting in fibrin thrombi, gradually diminishing levels of clotting factors with increased risk of bleeding. Basically two types of DIC are distinguished: (1) chronic (compensated) - with alteration of laboratory values and (2) acute (non-compensated) - with severe clinical manifestations: bleeding, shock, acute renal failure (ARF), transient focal neurologic deficit, delirium or coma. Chronic DIC related to metastatic neoplasia is caused by pancreatic, gastric or prostatic carcinoma in most of the cases. Incidence rate of DIC is 13-30% in prostate cancer, among those only 0.4-1.65% of patients had clinical signs and symptoms of DIC. In other words, chronic DIC is developed in one of eight patients with prostate cancer. DIC is considered as a poor prognostic factor in prostatic carcinoma. The similar clinical and laboratory findings of TTP-HUS (thrombotic thrombocytopenic purpura - hemolytic uremic syndrome) and DIC makes it difficult to differentiate between them. A 71 years old male patient with known chronic obstructive pulmonary disease, benign prostatic hyperplasia, significant carotid artery stenosis, gastric ulcer and alcoholic liver disease was admitted to another hospital with melena. Gastroscopy revealed intact gastric mucosa and actually non-bleeding duodenal ulcer covered by clots. Laboratory results showed hyperkalemia, elevated kidney function tests, indirect hyperbilirubinemia, increased liver function tests, leukocytosis, anemia, thrombocytopenia and elevated international normalized ratio (INR). He was treated with saline infusions, four units of red blood cells and one unit of fresh frozen plasma transfusions. Four days later he was transported to our Institution with ARF. Physical examination revealed dyspnoe, petechiae, hemoptoe, oliguria, chest-wall pain and aggressive behavior. Thrombocytopenia, signs of MAHA (fragmentocytes and helmet cells in the peripheral blood), normal INR, elevated lactate dehydrogenase (LDH) and ARF suggested TTP-HUS. Hemodialysis and six plasmaferesis (PF) were carried out. After the fifth PF, skin manifestations of thrombotic microangiopathy occurred on the feet. Clotting analysis revealed elevated D-dimer (>5 μg/mL), normal fibrinogen (3.2 g/L), a slightly raised INR (1.36) and activated partial prothrombin time (APTT) (45.8 sec), normal reticulocyte (57 G/L) and a slightly low platelet count (123 G/L), which proved to be chronic DIC. Therapeutic dose of low-molecular-weight heparin (LMWH) was started. Elevated prostate-specific antigen (PSA) (109.6 ng/mL) suggested prostatic carcinoma. Prostate biopsy revealed adenocarcinoma (Gleason: 4+4 for left lobe and 3+3 for right lobe). Elevated alkaline phosphatase suggested metastases in the bone, which were confirmed by bone scintigraphy. Combined androgen blockade (CAB) was started. After three months follow-up our patient's status is satisfactory. PSA is in the normal range (4.6 ng/mL). Thrombocytopenia of uncertain origin with normal or raised INR, APTT, elevated D-dimer, normal fibrinogen and reticulocyte count prove the diagnosis of chronic DIC. This process warrants searching for metastatic neoplasia. Due to the relatively low serum levels of circulating procoagulant factors (e.g. tissue factor), therapeutic dose of LMWH can be used with good efficiency in chronic DIC with low risk of bleeding. Severe DIC as a complication of metastatic prostate cancer can be treated by androgen deprivation therapy (ADT) or CAB in combination with ketokonazole and concomitant use of supportive treatment. Deme D, Ragán M, Kovács L, Kalmár K, Varga E, Varga T, Rakonczai E. Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case.     

Disturbances of desmofibrinogenesis in pateints suffering from acute myeloblastic leukemia

Significantly decreased levels of blood plasma clotting factor XIII (FSF) were found in the blood of 20 patients with acute myeloblastic leukemia as compared to the control values. It was found that after administration of cytostatic drugs (Cerubidyne and Cytosar) FSF deficiency was higher. This effect was associated with a proteolytic activity detectable in plasma which destroys FSF in vitro. This proteolytic activity was neither inhibited by EACA nor by Trasylol. These results indicate that in patients with acute myeloblastic leukemia beside DIC the treatment with cytostatic drugs as well as the presence of proteases from leukemic cells in the plasma will cause an impairment of transformation of soluble fibrin polymer into insoluble desmofibrin.     

Pregnancy and acute baroreflex resetting in conscious rabbits

To test the hypothesis that acute resetting of baroreflex control of heart rate (HR) is enhanced during pregnancy, we determined whether the rightward shift in the baroreflex relationship between arterial pressure and HR after arterial pressure is raised [~25 mmHg for 30 min, due to infusion of phenylephrine (PE) or methoxamine (Meth)] is greater in late pregnant compared with nonpregnant conscious rabbits. Baroreflex function was assessed by monitoring HR responses to both stepwise steady-state changes (n = 14) and rapid ramp changes (n = 10) in arterial pressure. Pregnancy decreased reflex gain, increased reflex minimum HR, and shifted the curves to a lower pressure level, when either the steady-state or ramp method was used (all changes, P < 0.05). When PE was used to increase pressure, resetting of steady-state curves was observed both before and during pregnancy, but the magnitude of the resetting was less in the pregnant rabbits. Further inspection of the data revealed that the size of the shift in pregnant rabbits was inversely related to the dose of PE. Because the pressure rise was the same in all experiments, PE appears to nonspecifically counteract acute resetting. When Meth was used instead to increase pressure, resetting of steady-state curves was similar in pregnant and nonpregnant rabbits and was unrelated to dose. Similarly, when reflex curves were generated using the ramp method, and either Meth or low doses of PE were used to increase pressure, no differences in the degree of resetting were observed between pregnant and nonpregnant rabbits. In summary, high doses of PE counteract acute resetting of baroreflex control of HR. More importantly, while baroreflex function is depressed, the ability of the baroreflex to reset appears to be preserved during pregnancy.     

连续性肾脏替代疗法治疗重症急性胰腺炎的临床观察

目的观察连续性肾脏替代疗法（CRRT）治疗重症急性胰腺炎（SAP）患者的疗效及预后。方法回顾性分析广西医科大学第一附属医院ICU 2006年5月～2012年2月收治的22例SAP患者的临床资料,比较CRRT治疗前,治疗后3、5、7天患者生命征,APACHEⅡ评分及白细胞、SCr、血AMS、血气等变化,记录腹部症状并统计并发症及死亡率。结果 22例患者死亡4例,死亡率18.20%。22例患者均有急性肾损伤;急性肺损伤/急性呼吸窘迫综合征/肺部感染发生率为81.82%,其中胸腔积液50%;MODS 45.45%;感染性休克13.64%;急性肝损伤、胰性脑病均为9.09%;DIC、ACS均为4.55%。与治疗前相比,CRRT治疗3天后,T、RR、WBC、血AMS、血乳酸、APACHⅡ评分均下降（P〈0.05）,pH升高（P〈0.05）;5天后,脉搏、SCr、CRP均下降（P〈0.05）,PaO2/FiO2升高（P〈0.05）。3～5天后临床症状及体征改善。MAP呈下降趋势,但差异无统计学意义（P〉0.05）。结论 CRRT能快速有效改善SAP患者病情,稳定生命征、改善血气分析指标、清除体内代谢毒素,入住ICU的SAP患者及早进行CRRT的效果较好。     

Response of selected fetal organs to antineoplastic agents

This study was designed to quantitate the effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 5-(3,3-bis(2-chlorethyl)-1-triazeno)-imidazole-4-carboxamide (BIC) on growth and selected components of rat fetal organs. Twelve-day pregnant rats were given single intraperitoneal injections of 600 mg/kg of DIC and 900 mg/kg of BIC and autopsied on day 21 of gestation. Fetal liver, brain, kidney, and placenta were removed, weighed, and assayed for total DNA, RNA, and protein. DIC significantly reduced weight, total DNA, RNA, and protein of all four fetal organs as compared to age-matched controls. The brain was most severely affected by this compound. BIC also significantly reduced weight, DNA, RNA, and protein of fetal brain, kidney, and placenta, but in fetal liver only weight and total protein were significantly depressed, while DNA and RNA remained essentially unchanged. The effect of BIC was maximal on the placenta.     

Ventricular metastasis resulting in disseminated intravascular coagulation

BACKGROUND: Disseminated Intravascular Coagulation (DIC) complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC) has rarely been associated with DIC. CASE PRESENTATION: A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient. CONCLUSION: Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.     

Fibrinogen--proteolysis in acute myelogenous leukemia (AML)

Fibrinopeptides were measured as direct indices of thrombin, plasmin and elastase in plasma samples obtained from patients with AML. Peptide patterns observed were consistent with spontaneous or drug induced plasmin-specific fibrinogenolysis (AML FAB M 1/3), elastase mediated proteolysis (AML FAB M 3/4) or DIC (AML FAB 4/5). DIC was also observed in septic, agranulocytotic patients.     

Transgenerational consequences of acute antenatal stress in pregnant rats

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.     

Activation of the blood kallikrein-kinin system in disseminated intravascular coagulation in rats. The significance of the pulmonary component and an attempt at correction with aspirin

It has been shown that the development in animals of disseminated intravascular coagulation (DIC) caused by long-term intravenous infusion of thrombin was accompanied by appreciable activation of the kallikrein-kinin system, being characteristic of acute pathological processes. In the initial stages of the process development, prekallikrein and kallikrein inhibitor were observed to be secreted from the lungs to arterial blood. Further development of DIC led to the depletion of the reserves of the kinin system. Pretreatment with a single low dose of acetylsalicylic acid considerably reduced the total animals' lethality and postponed blood kinin system activation determined by the development of DIC.     

Detection of steroidogenic acute regulatory protein in equine ovaries

A steroidogenic acute regulatory (StAR) protein has been identified in several species as a probable important rate-limiting step in steroidogenesis. This protein is believed to be responsible for transporting cholesterol from the outer to the inner mitochondrial membrane. It is known that equine chorionic gonadotrophin (eCG) stimulates steroidogenesis in the corpora lutea of early pregnant mares and that eCG also upregulates StAR mRNA in bovine ovaries. In the present study, ovarian tissue from cyclic and early pregnant mares was immunostained to detect the distribution of the StAR protein. Western blot analysis was performed, followed by phosphor imaging to establish whether the onset of eCG secretion in pregnancy was associated with increased expression of the StAR protein. Immunostaining for StAR was confined to the theca interna of growing and preovulatory follicles, but 24 h after treatment with hCG, some granulosa cells were positively stained. Positive staining was confined to the large luteal cells of the equine corpus luteum. There was no difference in the distribution of immunostaining before or after onset of eCG secretion in pregnant mares, but increased amounts of StAR were detected in corpora lutea from mares at day 40 or day 41 of pregnancy compared with non-pregnant mares and mares at days 20-30 of pregnancy.     

Greater numbers of nucleotide substitutions are introduced into the genomic RNA of bovine viral diarrhea virus during acute infections of pregnant cattle than of non-pregnant cattle

ABSTRACT: BACKGROUND: Bovine viral diarrhea virus (BVDV) strains circulating in livestock herds show significant sequence variation. Conventional wisdom states that most sequence variation arises during acute infections in response to immune or other environmental pressures. A recent study showed that more nucleotide changes were introduced into the BVDV genomic RNA during the establishment of a single fetal persistent infection than following a series of acute infections of naive cattle. However, it was not known if nucleotide changes were introduce when the virus crossed the placenta and infected the fetus or during the acute infection of the dam. METHODS: The sequence of the open reading frame (ORF) from viruses isolated from four acutely infected pregnant heifers following exposure to persistently infected (PI) calves was compared to the sequences of the virus from the progenitor PI calf and the virus from the resulting progeny PI calf to determine when genetic change was introduced. This was compared to genetic change found in viruses isolated from a pregnant PI cow and its PI calf, and in three viruses isolated from acutely infected, non-pregnant cattle exposed to PI calves. RESULTS: Most genetic changes previously identified between the progenitor and progeny PI viruses were in place in the acute phase viruses isolated from the dams six days post-exposure to the progenitor PI calf. Additionally, each progeny PI virus had two to three unique nucleotide substitutions that were introduced in crossing the placenta and infection of the fetus. The nucleotide sequence of two acute phase viruses isolated from steers exposed to PI calves revealed that six and seven nucleotide changes were introduced during the acute infection. The sequence of the BVDV-2 virus isolated from an acute infection of a PI calf (BVDV-1a) co-housed with a BVDV-2 PI calf had ten nucleotides that were different from the progenitor PI virus. Finally, twenty nucleotide changes were identified in the PI virus of a calf born to a PI dam. CONCLUSIONS: These results demonstrate that nucleotide changes are introduced into the BVDV infecting pregnant cattle at rates of 2.3 to 8 fold higher then during the acute infection of non-pregnant animals.     

Serum concentrations of immunoglobulins and acute phase proteins in Nigerian women with preeclampsia

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed based on a triad of hypertension, significant proteinuria and rapidly increasing edema during gestation. The factors that initiate preeclampsia are unknown and still a subject of intense clinical research. The objective of this study is to provide additional immunological information about preeclampsia. To achieve this, humoral immunochemical parameters such as three classes of immunoglobulin (IgA, IgG and IgM) and three acute phase proteins (alpha 2-macroglobulin, haptoglobin and transferrin) were measured by single radial immunodifussion method in 32 pregnant women with preeclampsia, 36 pregnant women without preeclampsia and 24 non-pregnant women (controls). Total protein in the urine was also determined by spectrophotometric method. In women with preeclampsia, the levels of IgG, IgA, transferrin and alpha 2-macroglobulin were significantly reduced compared with subjects with normal pregnancy, but the level of haptoglobin was significantly raised in preeclampsia compared with women having normal pregnancy. Urinary total protein and IgG were significantly raised in Nigerian women with preeclampsia compared with non-pregnant controls. There were significant negative correlations between serum IgG, IgA and urinary protein. The possible involvement of immunoglobulins and acute phase proteins in preeclampsia is discussed.     

Comparative evaluation of whole blood D-dimer test to plasma D-dimer test for diagnosis of disseminated intravascular coagulation

Three rapid D-dimer test methods were compared for the diagnosis of acute disseminated intravascular coagulation (DIC). These were (a) SimpliRED, an autologous red cell agglutination assay. (b) DIMERTEST latex agglutination assay, containing monoclonal antibody DD-3B6/22(6), and (c) D-DI latex agglutination assay containing mouse anti-human D-dimer monoclonal antibodies. The D-DI latex method having higher sensitivity (100%) and specificity (81%) in clinically acute DIC was postulated as the gold standard and compared with the other two methods. The results suggest that D-DI latex agglutination assay containing mouse anti-human D-Dimer monoclonal antibodies are the better assay methods amongst all the three kits analyzed. It is advisable to look for the nature of the antibody used to coat the latex particles in plasma based kits. In emergency setting RBC kits may be of some use as rapid diagnosis is advantageous.     

Isoenzyme pattern of serum beta-hexosaminidase in liver disease, alcohol intoxication, and pregnancy

The isoenzyme distribution of serum beta-hexosaminidase was studied in 11 pregnant women, 18 patients with cirrhosis of the liver, 14 patients with cholestasis, and 9 chronic alcoholics with acute ethanol intoxication. Serum beta-hexosaminidase activity was elevated in sera from all groups. The results of isoenzyme separation by isoelectric focusing demonstrated that the isoenzyme pattern in the different patient groups was similar to pregnancy with a preferential increase of isoenzyme forms with pI's between 5.6 and 6.8.     

Immune status and proinflammatury cytokines in pregnant women with acute cytomegalovirus infection

A total of 64 pregnant women aged 16-40 years with acute cytomegalovirus (CMV) infection were examined. CMV infection was diagnosed by the detection of anti- CMV IgM (by the enzyme immunoassay) or DNA by PCR in the blood. The immunophenotype of lymphocytes CD3+, CD4+, CD8+, CD16+, CD19+, IgG, IgM, IgA and the spontaneous production of TNFalpha and IL-8 in the blood were studied. In pregnant women with CMV infection the presence of the immunosuppression of cell-mediated immunity reactions, the hyperproduction of Fc-receptors of natural killers, B lymphocytes (CD19+), the hyperglobulinemia of serum IgM and IgG, as well as the increased synthesis of proinflammatory cytokines--TNFalpha and IL-8--were established.     

Influence of acute heat stress on the development of GABAergic neurons in HPA-axies of mouse embryos

The damaging effects of acute heat stress in pregnant mice is well known, however, very little is known about the impact of heat on embryonic neurodevelopment and its dependence on the dam's physiological response to the stress. To study the changes in GABAergic neurons expression on the hypothalamo-pituitary-adrenocortical axis (HPA-axis), superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in mouse embryos on E13-17 following acute, maternal heat stress. Blood samples and amniotic fluid from pregnant mice, and homogenates of whole embryos and embryo brains were collected for SOD and MDA analyses. SOD and MDA activities were measured in embryo and the sections by staining with anti-γ-aminobutyric acid-A- α1 receptor (GABAA receptor- α1), anti-γ-aminobutyric acid-B-1 receptor (GABAB receptor-R1) and anti-glutamate decarboxylase-65(GAD-65) antibodies. After the pregnant mice underwent acute heat stress on E13, the embryonic GABAergic neurons and GABA receptor expression were triggered immediately as a result of induction of the HPA-axis. This expression recovered to normal levels consistent with the control groups. However, the expression of the GABAA receptor in embryonic adrenal gland decreased continually. The SOD activity decreased in the embryonic brain and increased in the amniotic fluid after the heat stress, whereas the MDA levels increased in the maternal plasma only. Therefore, the GABAergic neurons in the developing HPA-axis of the embryos are susceptible to heat stress and the enhancement of SOD activities in the amniotic fluid might be a protective mechanism.     

On the causes of intra- and post-operative consumption coagulopathies and postoperative thromboembolism]

The determination of the onset of a disseminated intravascular coagulation (DIC) is examined shortly after its intraoperative andpost-operative dissolution with the help of easily performable haematological and physiological clotting tests in 20 patients. In this connection the operation is appreciated as a model even for other processes defined at the beginning, where DIC can be observed. Whereas the aethanol test, the determination of fibrinogen split products (FSP) and the euglobulin lysis time indicate the beginning of DIC more clearly in the form of average values, the aethanol test, partial thromboplastin time and thrombin time have a prognostic value for each patient. As it is too time consuming to determine FSP, the counting of basophilie granulocytes may be used for the diagnosis. In the initial phase of and post-operative DIC will determine the essential share of predisposition to post-operative thromboembolism.