Disseminated intravascular coagulation

The diagnosis of disseminated intravascular coagulation associated with intracranial pathology is discussed. This pathological entity is characterized by a diffuse bleeding diathesis. Laboratory studies suggest a consumption of all clotting and fibrinolytic factors with an elevation of fibrin split products as a sign of the fibrinolytic activity. The treatment consists of the administration of packed platelets and fresh frozen plasma to replace the consumed coagulation factors. Heparinization is recommended early to prevent further consumption of coagulation factors and epsilon-aminocaproic acid is recommended later after acute fibrinolysis is diagnosed. Constant coaguloanalytic monitoring is necessary. Although the etiology with massive injury to brain tissue is possibly secondary to autotransfusion of brain tissue thromboplastin, other causes such as hypotension, anoxia, acidosis and hemolysis must be considered.     

Disseminated intravascular coagulation. Objective criteria for diagnosis and management

Current concepts of the cause, pathophysiology, clinical and laboratory diagnosis, and management of fulminant and low-grade DIC have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. In this discussion, objective clinical and laboratory criteria for a diagnosis of DIC have been delineated, thus eradicating unnecessary confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, cause of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for severity of DIC and objective criteria for defining a response to therapy. Also, because it is often difficult for the individual physician to decide when to stop often extensive therapy, objective criteria whereby therapy may be stopped, as continuation is likely fruitless, have been presented as a guideline. Lastly, it should be appreciated that many syndromes that are often organ specific share common pathophysiology with DIC but are typically identified as an independent disease entity, such as hemolytic uremic syndrome, adult shock lung syndrome, eclampsia, and many other isolated organ-specific disorders.     

Disseminated intravascular coagulation and status epilepticus

Status epilepticus has been associated with disseminated intravascular coagulation (DIC), but little is known regarding the pathogenesis of this uncommon association. We describe a 41-year-old woman with status epilepticus resulting in death in whom laboratory data demonstrated profound activation of the coagulation and fibrinolytic systems; autopsy findings were consistent with DIC. The occurrence of DIC in status epilepticus may be related to widespread endothelial damage secondary to seizure-induced hyperpyrexia. Body temperature should be closely monitored in patients with prolonged seizures.     

Disseminated intravascular coagulation and hyperfibrinolysis in dogs with metastasizing mammary carcinoma

The alterations of the haemostatic system (platelet count, activated partial thromboplastin time [APTT], thromboplastin time [standard test, modified test], thrombin time, fibrinogen concentration, activity of the coagulation factors II, V, VII, X, VIII:C, IX, XI, XII, of prekallikrein, high molecular weight kininogen, antithrombin III, protein C, plasminogen and alpha 2-plasmin inhibitor, concentration of soluble fibrin and fibrin(ogen) degradation products [FDP], resonance thrombogram) were described in seven dogs with haemorrhagic diathesis in consequence of an infiltrative, growing mammary carcinoma with multifocal invasion of lymphatic and blood vessels. In most of the cases metastases in different organs could be demonstrated. In every case a serious stage of disseminated intravascular coagulation and hyperfibrinolysis was existent. This was indicated by the distinctly increased concentration (p < 0.0001) of soluble fibrin (27.7 [16.0-79.2] micrograms/ml, median [minimum-maximum], reference range [RR.]: < 9.4 micrograms/ml) and FDP (340 [50-860] micrograms/ml, RR.: < 18 micrograms/ml) as well as a diminished plasma level of nearly all components of the coagulation and fibrinolytic system concerning especially the concentration of fibrinogen (0.16 [0.01-0.46] g/l, RR.: 1.17-3.09 g/l), the activity of factors V (30 [21-40]%, RR.: 75-158%) and VIII:C (9 [4-16]%, RR.: 72-136%) as well as the activity of protein C (8 [3-13]%, RR.: 68-139%) (each: p < 0.0001).     

Disseminated intravascular coagulation in a case of adult onset Still's disease

We report a 82-year-old woman with adult onset Still's disease (AOSD), who presented with high fever, skin rash, swollen axillary lymph nodes, accelerated erythrocyte sedimentation rate, leukocytosis, abnormal liver function tests, hypoalbuminemia, negative antinuclear antibody and rheumatoid factor, and lack of renal involvement. Disseminated intravascular coagulation (DIC) was also diagnosed on admission. An antipyretic relieved high fever and DIC soon improved. Three years later, AOSD relapsed accompanied by hypercoagulation and hyperfibrinolysis. The patient developed subdural hematoma and DIC due to a brain contusion. High titers of serum soluble adhesion molecules and soluble thrombomodulin were noted on the first episode of DIC. These findings indicated that endothelial cells were damaged in AOSD complicated by DIC.     

Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts

BACKGROUND: Intravascular fibrin deposition and platelet sequestration occur with porcine xenograft rejection by baboons. Disseminated intravascular coagulopathy may arise either as a direct consequence of the failure to fully deplete xenoreactive natural antibodies and block complement, or because of putative cross-species molecular incompatibilities in this discordant species combination. METHODS: Three baboons were conditioned with retrovirally transduced autologous bone marrow to induce tolerance to swine antigens. Xenoreactive natural antibodies and complement were depleted by plasmapheresis and the use of Gal alpha1-3Gal column adsorptions; baboons were then splenectomized and underwent renal xenografting from inbred, miniature pigs. Soluble complement receptor type-1 with protocol immunosuppression (mycophenolate mofetil, 15-deoxyspergualin, steroids, and cyclosporine) was administered. RESULTS: A bleeding diathesis was clinically evident from days 5 to 12 after transplantation in two baboons. Low levels of circulating C3a, C3d, and iC3b were measured despite the absence of functional circulating complement components. Profound thrombocytopenia with abnormalities in keeping with disseminated intravascular coagulopathy were observed. Prolongation of prothrombin and partial thromboplastin times was accompanied by evidence for tissue factor-mediated coagulation pathways, high levels of thrombin generation (prothrombin fragment F(1+2) production and thrombin-antithrombin complex formation), fibrinogen depletion, and production of high levels of the fibrin degradation product D-dimer. Importantly, these disturbances resolved rapidly after the excision of the rejected xenografts in two surviving animals. Histopathological examination of the rejected xenografts confirmed vascular injury, fibrin deposition, platelet deposition, and localized complement activation. CONCLUSIONS: Systemic coagulation disturbances are associated with delayed xenograft rejection.     

Disseminated intravascular coagulation in nonocclusive mesenteric ischemia: the lack of specificity of fibrin thrombi in intestinal infarction

The significance and frequency of fibrin thrombi (FT), the pathological hallmark of disseminated intravascular coagulation (DIC), in ischemic intestine were analyzed in a retrospective study of the infarcted bowel of patients with occlusive mesenteric ischemia (OMI) and nonocclusive mesenteric ischemia (NOMI). Representative intestinal sections were studied from 10 patients with NOMI of the small and/or large bowel and 12 patients, with OMI of varied etiology. Three patients with inflammatory bowel disease and 1 patient with DIC and bowel necrosis were also studied. Routine hematoxylin and eosin stains for fibrin were prepared for each specimen. The number of FT was quantitated. FT were identified in each of the 10 cases of NOMI; however in only 2 were they prominent. FT were identified in 6 of the 12 cases of OMI and in 4 of these 6 they were a prominent feature. Rare FT were present in the cases of inflammatory bowel disease and did not correlate with the inflammatory process. No FT were present in the intestinal sections of the DIC case. FT are a nonspecific feature of necrosis and can be identified in both occlusive and nonocclusive ischemic bowel disease. Their presence in the intestine of NOMI therefore cannot be used to implicate DIC as the primary cause of this entity.     

Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis

OBJECTIVE: To compare the construct validity and sensitivity to change of 2 spondylitis-specific measures of functional disability, the Health Assessment Questionnaire Disability Index modified for the spondyloarthropathies (HAQ-S) and the Dougados Functional Index, with 2 more generic instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales-2 (AIMS2), in patients with ankylosing spondylitis (AS). METHODS: Construct validity was assessed in 2 ways: (1) by comparisons of the cross sectional correlations between each functional disability instrument and 6 measures of physical impairment in 216 patients, and (2) by relating changes over time in the HAQ-S and the Functional Index with changes in patient reported pain and stiffness in 153 patients followed for at least 2 years. Sensitivity to change was measured from the responses of 155 patients who reported a qualitative change in the activity of their AS during followup. RESULTS: Most patients had mild functional disability, with median scores of 0.5 on the HAQ-S (possible range 0-3), 0.375 on the HAQ (possible range 0-3), 11 on the Functional Index (possible range 0-40), and 5 on the AIMS2 (possible range 0-60). Scores on the HAQ-S (R2 = 0.24) and the unmodified HAQ (R2 = 0.18) were more highly correlated with measures of physical impairment than were scores on the AIMS2 (R2 = 0.10) or the Functional Index (R2 = 0.09). Changes over time in the HAQ-S and HAQ were more closely related to changes in pain and stiffness than were changes in the Functional Index. The HAQ-S and HAQ were also more sensitive to change than the Functional Index. CONCLUSION: The HAQ-S showed greater construct validity and sensitivity to change than the Functional Index, but performed similarly to the unmodified HAQ.     

Diagnosis of disseminated intravascular coagulation

The variations of the measured dose rate in air should be recognized especially where background radiation is used as a comparative benchmark to assess radiation surveillance and environmental remediation work. In this note, the natural variations of the combined gamma and cosmic-ray background air-dose rate as measured by lithium fluoride thermoluminescence dosimeters are reported. The dosimeters were deployed monthly at locations within 150 km of the Environmental Measurements Laboratory in New York City. Urban and suburban stations were established with simultaneous indoor and outdoor measurements at some locations. Measurements were obtained over 10 to 18 years. The mean air-dose rates from the six outdoor and four indoor stations vary from 50.8 to 123.1 nGy h(-1). The range of the annual dose rates expressed as a percent-difference of the minimum and maximum is 5.3 to 18.0%. Commonly, 1-mo deviations from the long term mean of about +/-10 to +/-25% are observed. An abrupt decrease in the annual dose rate at one of the measurement sites was attributed to a minor relocation of a dosimeter. Structural shielding factors for the first and second floors of a residence are reported. The ground level location of a dosimeter inside another residence apparently resulted in a very high shielding factor. Finally, a gradual decrease of the dose rate at most of the stations is shown to exist (approximately -0.3 nGy h(-1) y(-1) for the outdoor stations). Plausible causes of this trend are briefly discussed.     

Cor pulmonale: pathophysiology and management

Pulmonary disease may set in motion a chain of events that ultimately leads to hypertrophy--or even failure--of the heart's right ventricle. The most common cause is chronic obstructive disease, which deprives the lungs of oxygen and produces pulmonary hypertension. But other disorders that raise pulmonary artery pressure also may be responsible. The thin right ventricle, which must work harder to overcome this increased resistance, ends up resembling the thick left ventricle. Comprehensive treatment of the primary lung condition at home usually enables the patient with chronic cor pulmonale to be more active and prevents frequent hospitalizations. Controlled-dose supplemental oxygen therapy is particularly effective, according to recent studies. Bronchospasm or bronchial infection super-imposed on the chronic lung condition may prove too much for the already strained right ventricle. Right ventricular failure calls for hospitalization and vigorous treatment, which may include mechanical ventilation, phlebotomy, antibiotics, steroids, digitalis, diuretics, and correction of electrolyte disturbances.     

Disseminated intravascular coagulation (D.I.C.) and fibrinolysis in patients with acute leukemia (author's transl)

Biological symptoms of D.I.C. were investigated in 43 patients with acute leukemia. Ten of them were found to be positive either at the onset or at the relapse of the disease and in some cases D.I.C. was triggered by chemotherapy. Among the ten positive cases 3 patients had an acute promyelocytic leukemia, 4 had an acute lymphoblastic leukemia, 2 a myeloblastic and 1 a monoblastic leukemia. D.I.C. was found either in patients with an hypercellular form of the disease or in patients with a normal or low white cell count. Symptoms of D.I.C. in acute leukemia must be systematically sought at the onset and during treatment by chemotherapy and treated with heparin and platelet transfusions as it is now admitted for acute promyelocytic leukemia.