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Hematology AND DIC [keywords]
- Quantitative optical microscopy: measurement of cellular biophysical features with a standard optical microscope. [Journal Article]
- J Vis Exp 2014; (86)
We describe the use of a standard optical microscope to perform quantitative measurements of mass, volume, and density on cellular specimens through a combination of bright field and differential interference contrast imagery. Two primary approaches are presented: noninterferometric quantitative phase microscopy (NIQPM), to perform measurements of total cell mass and subcellular density distribution, and Hilbert transform differential interference contrast microscopy (HTDIC) to determine volume. NIQPM is based on a simplified model of wave propagation, termed the paraxial approximation, with three underlying assumptions: low numerical aperture (NA) illumination, weak scattering, and weak absorption of light by the specimen. Fortunately, unstained cellular specimens satisfy these assumptions and low NA illumination is easily achieved on commercial microscopes. HTDIC is used to obtain volumetric information from through-focus DIC imagery under high NA illumination conditions. High NA illumination enables enhanced sectioning of the specimen along the optical axis. Hilbert transform processing on the DIC image stacks greatly enhances edge detection algorithms for localization of the specimen borders in three dimensions by separating the gray values of the specimen intensity from those of the background. The primary advantages of NIQPM and HTDIC lay in their technological accessibility using "off-the-shelf" microscopes. There are two basic limitations of these methods: slow z-stack acquisition time on commercial scopes currently abrogates the investigation of phenomena faster than 1 frame/minute, and secondly, diffraction effects restrict the utility of NIQPM and HTDIC to objects from 0.2 up to 10 (NIQPM) and 20 (HTDIC) μm in diameter, respectively. Hence, the specimen and its associated time dynamics of interest must meet certain size and temporal constraints to enable the use of these methods. Excitingly, most fixed cellular specimens are readily investigated with these methods.
- A case of thrombotic microangiopathy/microangiopathies. [JOURNAL ARTICLE]
- Blood Coagul Fibrinolysis 2014 Mar 7.
We report a case of Streptococcus pneumonia sepsis-associated disseminated intravascular coagulation (DIC) with features of acute renal failure and microvascular thrombosis characterized by skin purpura and bilateral foot necrosis. The persistence of laboratory features of microangiopathic hemolytic anemia despite aggressive correction of DIC-associated coagulopathy suggests the possibility of an additional concomitant microangiopathic process. Here, we discuss the management and diagnostic approach, particularly highlighting the difficulties in making a definitive diagnosis. Although unconfirmed, our differentials include the concomitant process of sepsis-induced DIC occurring together with an indeterminate form of plasmapheresis and plasma exchange-responsive thrombotic microangiopathy, processes which are previously believed to be mutually exclusive.
- Elevated fibrin-related markers in patients with malignant diseases frequently associated with disseminated intravascular coagulation and venous thromboembolism. [Journal Article, Research Support, Non-U.S. Gov't]
- Intern Med 2014; 53(5):413-9.
Many patients with malignant diseases are frequently complicated with some type of thrombosis, such as venous thromboembolism (VTE) or disseminated intravascular coagulation (DIC).This retrospective study was designed to examine the frequency of thrombosis in 478 patients with malignant diseases in comparison to that observed in 121 patients without malignant diseases and to evaluate the efficacy of fibrin-related markers (FRMs), such as soluble fibrin, fibrinogen and fibrin degradation products and D-dimer, in diagnosing thrombosis.The frequency of thrombosis, including 62 cases of VTE, 63 cases of DIC and nine cases of cerebrovascular thrombosis, was significantly higher in the patients with malignant diseases (28.0%) than in the patients without malignant diseases (12.5%). DIC was frequently detected in the patients with hepatic cell cancer and hematopoietic malignancy, while VTE was frequently observed in the patients with colon cancer, breast cancer and urinary tract cancer. The FRMs levels were significantly higher in the patients with thrombosis than in the patients without thrombosis. A receiver operating characteristic analysis showed these markers to be useful for diagnosing thrombosis.Patients with malignant diseases have a high risk of thrombosis, and elevated FRMs levels are useful for diagnosing thrombosis in patients with malignant diseases.
- Primary intrarenal neuroblastoma with hypertension and disseminated intravascular coagulation. [Journal Article]
- Case Rep Oncol Med 2013.:684939.
The primary intrarenal neuroblastoma (IRNB) is a rare condition. Intrarenal neuroblastoma typically results from direct renal invasion from an adrenal neuroblastoma, but true intrarenal neuroblastoma originates either sequestered adrenal rests during the fetal life or intrarenal sympathetic ganglia. Clinical, radiological, and pathological correlation is very essential for diagnosis and appropriate management of this type of unusual cases. The distinction of this rare tumor from Wilms' tumor is an important challenge since both tumors have major differences in prognostic and therapeutic response. We present a 3-year-old boy of primary intrarenal neuroblastoma with extensive abdominal and mediastinal mass, persistent hypertension, and disseminated intravascular coagulation (DIC).
- Effective control of relapsing disseminated intravascular coagulation in a patient with decompensated liver cirrhosis by recombinant soluble thrombomodulin. [Journal Article]
- Intern Med 2014; 53(1):29-33.
A 70-year-old Japanese man was hospitalized for expanding purpura and chronic disseminated intravascular coagulation (DIC) caused by decompensated liver cirrhosis. As there are no effective treatments for chronic DIC caused by liver cirrhosis, we decided to administer recombinant human soluble thrombomodulin (rhsTM) after he provided informed consent. The DIC was rapidly improved; however, the purpura and coagulopathy recurred after two months, and repeated rhsTM treatments were required. The rhsTM treatment sufficiently controlled the coagulopathy for two years, without any complications, including bleeding. This is the first report demonstrating that rhsTM can be administered safely and repeatedly to a patient with decompensated liver cirrhosis, and that it appears to be associated with a favorable outcome.
- Elevated plasma levels of soluble platelet glycoprotein VI (GPVI) in patients with thrombotic microangiopathy. [Journal Article, Research Support, Non-U.S. Gov't]
- Thromb Res 2014 Mar; 133(3):440-4.
Thrombotic microangiopathy (TMA) is caused by various conditions, such as decreased a ADAMTS13 level, activated or injured vascular endothelial cells or activated platelets. This study examined the soluble platelet glycoprotein VI (sGPVI) levels in patients with TMA to evaluate the activation of platelets in thrombotic states.The plasma levels of sGPVI, ADAMTS13 activity, von Willebrand factor (VWF) and VWF propeptide (VWFpp) were measured in patients with TMA.The plasma levels of sGPVI were significantly higher in postoperative patients, patients with TMA and those with disseminated intravascular coagulation (DIC) than in those without thrombosis. The plasma levels of sGPVI were the highest in patients with TMA without markedly reduced ADAMTS13 and those were significantly reduced after plasma exchange.The measurement of sGPVI level is therefore considered to be important for the diagnosis and evaluation of TMA.
- Current consideration and management of disseminated intravascular coagulation. [Journal Article]
- Hematology Am Soc Hematol Educ Program 2013.:286-91.
Disseminated intravascular coagulation (DIC) is a devastating clinical condition that is characterized by the loss of normal hemostatic control in response to sustained and systemic cell injury. The inciting injury may be from infection, trauma, or malignancy, but the consequent pathophysiology is multifactorial involving intertwined feedback loops between the coagulant, immune, and inflammatory pathways. Central to this is thrombin generation, but the ubiquitous nature of its in vivo functional consequences can make it difficult to dissect away the separate but overlapping components to the clinical problem. Therefore, early recognition and resolution of the precipitating events leading to DIC remains the central tenet to clinical care. This article refreshes our conceptual understanding of DIC pathogenesis and draws in recent advances in the cycle of cell death caused by extracellular nuclear proteins. It also aims to delineate recognition of response pathways that can be predominantly procoagulant or profibrinolytic to enable a more personalized and evidence-based approach to be delivered to the patient with DIC.
- Microparticle bearing tissue factor: a link between promyelocytic cells and hypercoagulable state. [Journal Article, Research Support, Non-U.S. Gov't]
- Thromb Res 2014 Mar; 133(3):433-9.
Patients with hematological malignancies have a 28-fold increased risk of venous thromboembolism (VTE). Among patients with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE is 5.2%. Several studies suggest that microvesicles (MVs) harboring TF may play a role in VTE and disseminated intravascular coagulation (DIC) in acute promyelocytic leukemia (APL). The aim of this study was to assess the capacity of untreated (APL) cells to shed procoagulant MVs. APL cells (NB4 and HL-60 cell lines) and MVs were separated by filtration (0.1-0.22-0.45-0.65 μm). The procoagulant activity (PCA) was assessed by thrombin generation assay (TGA). Alternatively, MVs were incubated with anti-Tissue Factor (TF) antibodies, with annexin V to assess the contribution of TF and phospholipids (PL) to the PCA, respectively. NB4 cells had a high PCA mainly triggered by MVs of size under 0.45 μm. The PCA of MVs was related to the expression of active TF and PL. HL-60 cells had a weaker PCA since TF is mostly present in its inactive form. Moreover, HL-60 do not produce MVs<0.65 μm associated with PCA. MVs could have a predicting value for VTE and DIC in patients with acute promyelocytic leukemia and could inform physicians about the optimal use of a thromboprophylaxis.
- Schistocytes in disseminated intravascular coagulation. [JOURNAL ARTICLE]
- Int J Lab Hematol 2013 Nov 22.
The presence of schistocytes on the peripheral blood film during disseminated intravascular coagulation (DIC) remains controversial.We examined schistocytes count on blood films from 35 DIC patients and checked morphological anomalies of all RBCs.Thirty of 35 patients presented with schistocytes and 22 with acanthocytes, which was the commonest shape anomaly. Mean percentage ± standard deviation was 0.33 ± 0.38%, median value was 0.1%, and range was 0-1.4%. The patients with schistocytes ≥ 1% had circumstances frequently associated with increased schistocytes count (promyelocytic leukaemia, pregnancy, severe infection).Schistocytes were thus frequently observed in DIC patients, usually with low percentage, within or close to the reference range (<0.5%). Schistocytes measurement is not a clue test for the initial diagnosis of DIC, but might be of clinical value to suggest an associated or underlying thrombotic microangiopathy if ≥ 1%.
- Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC). [Journal Article, Review]
- Pediatr Clin North Am 2013 Dec; 60(6):1337-48.
A complete blood cell count (CBC) is a frequent test sent to aid in the diagnostic evaluation of ill patients. Not uncommonly hematologic abnormalities may be the first sign of an underlying systemic disorder. The astute clinician needs to understand how systemic disease can affect the CBC to direct further diagnostic investigations. This article focuses on the 2 most common acquired anemias including iron deficiency and anemia of inflammation as well as disseminated intravascular coagulation.