Purpura fulminans induced by disseminated intravascular coagulation following infection in 2 unrelated children with double heterozygosity for factor V Leiden and protein S deficiency

Purpura fulminans is associated with homozygous protein C and homozygous protein S deficiency or may follow bacterial or viral infections. We present 2 children from 2 unrelated Arab families with purpura fulminans who were double heterozygotes for factor V Leiden inherited from their fathers and protein S deficiency inherited from their mothers. No previous thrombotic events have occurred in either patient or their respective family members. In one patient sepsis accompanied by disseminated intravascular coagulation appeared to be the trigger of purpura fulminans. In the other patient varicella infection preceded purpura fulminans and was also associated with disseminated intravascular coagulation. This report emphasizes the need for evaluation of hereditary defects in the inhibitory mechanisms of blood coagulation in patients with purpura fulminans at any age.     

Two fetal deaths associated with maternal sepsis and with thrombosis of the intervillous space of the placenta

The placental pathology in two second trimester fetal losses associated with mild maternal disseminated intravascular coagulation are reported. Case one had a dental abscess, a leukocytosis of 36300 white blood cells/m, and evidence of mild consumptive coagulopathy at 20 weeks. Case two had septic findings including disseminated intravascular thrombosis associated with pyelonephritis. The placentae had extensive intervillous thrombosis at the periphery of spiral arterial flow. It is hypothesized that in mild disseminated intravascular coagulation, the trophoblast inhibits fibrinolysis, favouring thrombosis perhaps due to production of plasminogen activator inhibitor.     

Purpura fulminans in the newborn. Report of two cases successfully treated with heparin and antithrombin III

Purpura fulminans is a rare form of disseminated intravascular coagulation characterized by rapidly progressive purpuric lesions, hypotension and, in some cases, fever. In neonates, purpura fulminans usually develops following deficiency of anticoagulant protein C or S, although acquired forms have been described. The management of disseminated intravascular coagulation is still controversial, with some studies finding a positive effect of anticoagulants and others showing no effect or even a detrimental one. Therefore, at present, management is limited to the treatment of underlying disease and replacement of clotting factors. Personal experience is reported on the efficacy of heparin in combination with antithrombin III in the treatment of purpura fulminans in two preterm neonates who did not have inherited deficiency of protein C or S and developed the disease possibly following prolonged labor (36 hours) in the first case, and maternal neoplasia, in the second. Both neonates presented with widespread cyanotic areas rapidly evolving in purpuric lesions and hemorrhagic bullae. Laboratory tests (prolonged prothrombin and partial thromboplastin time, fibrinogen and antithrombin III concentrations below normal ranges, d-dimer highly positive) were consistent with disseminated intravascular coagulation. In both cases anticoagulant treatment with heparin (50 UI/kg in bolus followed by 15 UI/kg/h) and antithrombin III was associated with resolution of disseminated intravascular coagulation and prompt amelioration of the purpuric lesions, without apparent side effects.     

Purpura fulminans in pneumococcal sepsis: case report and review

Purpura fulminans is classically defined by ecchymotic skin lesions, fever, and hypotension. The majority of cases occur in association with bacterial sepsis, and disseminated intravascular coagulation (DIC) is usually present. Prompted by our experience with a patient with pneumococcal sepsis and purpura fulminans in whom hypotension was never observed, we evaluated the important parameters of sepsis in reports of this syndrome. 42 additional cases of pneumococcal bacteremia and purpura fulminans were identified. Hypotension was present in only 51%. Although DIC was present in 85% of patients, hypofibrinogenemia was documented in only 26%. By contrast, both hypotension and hypofibrinogenemia are present in the vast majority of patients described with purpura fulminans in association with meningococcal sepsis. These data confirm that hypotension is not a necessary feature of the syndrome of purpura fulminans associated with pneumococcal sepsis and suggest further that qualitative or quantitative differences exist in the DIC cascade of pneumococcal vs meningococcal sepsis.     

Severe cutaneous and venous damage after DIC therapy

A 79-year-old woman with skin ulcers caused by disseminated intravascular coagulation (DIC) therapy is reported. The patient had been treated by injection of drugs, including gabexate mesilate, into the right great saphenous vein. The maximum concentration of gabexate mesilate was calculated as 0.893%. Although the drugs did not extravasate, purpura initially appeared around the affected vein, followed by brown pigmentation with infiltration and ulcers with widely necrotic tissue from the middle portion of her thigh to the malleolus along her right great saphenous vein. As the ulcer showed no tendency to heal for more than 3 months, surgical debridement and skin grafts were performed.     

Aorto-iliac thrombosis in a foal

A six-day-old Missouri foxtrotter colt was examined because it had had diarrhoea since it was 24 hours old. A diagnosis of colitis, septicaemia, and disruption of the arterial blood flow to the pelvic limbs was made on the basis of clinical and laboratory findings. Despite intensive medical therapy, the foal died 13 hours after being examined. Postmortem examination revealed diffuse fibrinous enteritis with lymphoid necrosis, multifocal fibrinonecrotic typhlocolitis, disseminated intravascular coagulation, and a large occluding thrombus at the aortic termination. The results of bacteriological culturing supported the diagnosis of septicaemia leading to activation of the clotting cascade, disseminated intravascular coagulation, aorto-iliac thrombosis and infarction of the pelvic limbs.     

The effect of 17 beta-estradiol and endothelin 1 on prostacyclin and thromboxane production in human endothelial cell cultures

The authors present an account on a neonate with dextro-lateral renal venous thrombosis. They focus attention on the diagnostic and therapeutic procedure and compare it with available data from the literature. Contrary to data in the literature, they did not observe in the acute stage of renal venous thrombosis signs of disseminated intravascular coagulation in peripheral blood. It did not prove possible to elucidate the action of any of the factors leading to the development of renal venous thrombosis. After evidence of permanent functional loss of the right kidney nephrectomy was performed. Histopathological examination provided evidence of obliterating thrombosis of the renal veins with partial recanalization and calcifications. The authors emphasize the necessity of early diagnosis of renal venous thrombosis and adequate treatment based on the revealed findings.     

Blood coagulation disorders in infants with infectious gastroenteritis

The study included 28 infants with infectious gastroenteritis who evolved with disturbances of coagulation and in whom laboratory tests were practiced by micromethods through capillary puncture. The most frequently seen abnormality was a combination of vitamin K dependent factors deficiency with thrombocytopenia. Another observation in our study is that hypofibrinogenemia in infants with infectious gastroenteritis is not always secondary to disseminated intravascular coagulation. A decrease in fibrinogen in these cases is explained by a lack in synthesis of this factor in infants with malnutrition since out of 16 malnourished infants, 75% evolved with hypofibrinogenemia, while eutrophic infants evolved with normal fibrinogen. The disseminated intravascular coagulation syndrome was seen more frequently in patients with infectious gastroenteritis complicated with septicemia and shock, 57% of the patients did not show manifestations of bleeding nor of thrombosis which justifies in these cases a systematic investigation of the coagulation mechanism.     

Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones

We report the cases of three patients with anorexia nervosa (AN) who each recovered rapidly after experiencing a life-threatening episode with severe thrombocytopenia. All three cases were the typical restricting-type of AN, occurring in adolescence. They refused to be admitted to a hospital until their general condition had been severely deteriorated. Their lowest platelet counts were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal bleeding were observed. The bone marrow examination showed apparent hypoplasia in two patients. No evidence of disseminated intravascular coagulation or autoantibody to platelets was detected. The platelet counts recovered rapidly by water and nutritional supplementation. The recovery from the AN itself was excellent in all three patients without specific psychotherapy.     

Haematological abnormalities in acute pancreatitis. A prospective study

Twenty-five patients with acute pancreatitis were studied prospectively in the first week of their admission using haematological and coagulation tests. Platelet counts initially fell and later returned to admission levels. Rising levels of plasma fibrinogen were recorded. The kaolin cephalin clotting time was shorter than its control in twenty-one patients. Eighteen patients had elevated fibrinogen degradation products and fourteen had a positive ethanol gelation test. It is suggested that by taking into account the results in series of individual patients a degree of intravascular coagulation may be a common feature of acute pancreatitis. In one patient (presented in detail) strong evidence for disseminated intravascular coagulation was found     

Tissue factor pathway inhibitor: potential therapeutic applications

Tissue factor pathway of coagulation plays a dominant role during normal haemostasis. Tissue factor pathway inhibitor (TFPI), expressed primarily by the microvascular endothelium, appears to be the major physiologic inhibitor of TF-induced coagulation. TF-initiated coagulation also plays an important role in the pathophysiology of many diseases including coronary thrombosis, sepsis, disseminated intravascular coagulation, stroke, cancer, acute respiratory distress syndrome, and ischemia-reperfusion injury. Several animal studies have found a beneficial effect of anti-TF monoclonal antibodies and, recombinant TFPI in some of the above clinical conditions. rTFPI is presently being used in clinical trials in patients with sepsis and in those following microvascular surgery. This article discusses many of the animal studies addressing inhibition of TF-induced coagulation, as well as potential therapeutic uses of rTFPI in humans.     

Venous infarction of the adrenal glands

An investigation of 78 cases of adrenal haemorrhage and necrosis disclosed that 32 were examples of adrenal venous infarction. In all these cases there was thrombosis of the main adrenal vein and in most there was also thrombosis of the capsular veins, a finding which has not been well established. In a number of cases with venous infarction there was clinical and pathological evidence that disseminated intravascular coagulation (DIC) had occurred, but it appears that it was not the direct cause of venous thrombosis. The majority of cases of venous infarction occur in patients with severe infection, frequently of the respiratory tract. Venous infarction was found in five cases with hypothermia an association which had rarely been described, and in three of these there was evidence of DIC. This is apparently the first occasion on which DIC has been demonstrated in cases of hypothermia in man. The cause of venous thrombosis in the adrenal glands is obscure in most cases of venous infarction, although in three it was due to involvement by metastatic carcinoma. It is suggested that the factors responsible for the initiation of thrombosis in the adrenal veins are catecholamines, thrombin, fibrin and endotoxin. Localisation of the thrombi to the adrenal vein is due to the unique anatomical structure of the vein which, under certain circumstances, results in the local stasis of blood.     

Intravascular coagulation in surgical procedures on the abdominal aorta

A prospective study was performed on 32 consecutive patients undergoing elective operations on the abdominal aorta. Dacron prosthetic grafts were used to replace resected abdominal aortic aneurysms or to bypass aorta-iliac occlusive disease. Complete coagulation studies were performed preoperatively, immediately postoperatively and 24 hours postoperatively. Twenty to 30 per cent of the patients had significant postoperative alterations in prothrombin time, partial thromboplastin time and platelet count. Fibrin monomer, fibrin split products and plasminogen were abnormal in 40 to 80 per cent of the patients postoperatively. Results of preoperative studies showed no significant abnormalities. One of the 32 patients had mild clinical evidence of disseminated intravascular coagulation postoperatively, which was treated with 5 units of heparin per kilogram per hour. Results of the study indicate that aortic grafting procedures frequently produce intravascular coagulation, either local or disseminated. In most patients, this is offset by activation of the fibrinolytic system. However, clinically significant sequelae may result, requiring prompt recognition and treatment.     

Non-olfactorial discrimination between foods by the dog

Simple coagulation studies were carried out in 18 patients with advanced Trypanosoma gambiense infection. No evidence of disseminated intravascular coagulation was found. Many patients had a moderate degree of thrombocytopenia which may have been due to enhanced splenic trapping of platelets. Most patients had raised levels of fibrin degradation products in their cerebrospinal fluid, perhaps reflecting the presence of underlying cerebral and meningeal vascular damage. Addition of viable trypanosomes or of trypanosome extracts to human and rat blood did not produce significant thrombocytopenia in vitro.     

The semantics of addiction: moving beyond expert models to lay understandings

Disseminated intravascular coagulation (DIC) syndromes can be defined as the formation of fibrin deposits within the microcirculation, occurring in definite clinical situations. Their biological counterpart is a consumption coagulopathy. The clinical profiles of DIC have been well known for decades, are multiform and range from latency to overwhelming haemorrhagic diatheses, including also characteristic but rare situations, such as purpura fulminans, acral cyanosis and pictures resembling thrombotic thrombocytopenic purpura or haemolytic-uraemic syndrome. Biological tests of DIC show a consumption coagulopathy, displayed on the standard haemostasis sheet; along with signs of paracoagulation and/or of secondary fibrinolysis (FDP). New tests have recently been introduced: D-dimers are specific and sensible; Antithrombin-III, protein C and alpha 2-antiplasmin also can sometimes be useful. The knowledge of the pathophysiology of DIC has made advances with passing years. Fibrin deposits may be non-occlusive, and indeed they are swiftly removed by a secondary fibrinolysis. Except in very rare situations, such as those leading to a cortical renal necrosis, and perhaps in some ARDS, there is little evidence relating DIC to organ failure syndromes. Moreover, there is no clear relationship between the severity of the consumption coagulopathy and the prognosis. For instance, the mortality is much lower in abruptio placentae, where the coagulopathy is very severe, than in septic shock, where it is usually moderate. In septic shock, the disorders of haemostasis were related initially to a platelet activation, then to an activation of the contact system (releasing kinins and triggering complement cascade), and nowadays to the activation of the extrinsic coagulation system. The treatment of DIC is mainly the treatment of its cause. Indications for heparin therapy should be strictly limited to a few exceptional circumstances. When haemorrhagic diathesis threatens, FPC and/or platelet transfusion may be indicated. Aprotinin can be useful in rare cases of overwhelming secondary fibrinolysis. Trials with antithrombin-III or C1-esterase inhibitors are in progress.     

Non-bacterial thrombotic endocarditis: clinicopathologic correlations

Sixty-five cases of nonbacterial thrombotic endocarditis (NBTE) were discovered at autopsy during a 10 year period--an incidence of 1.6 per cent in the adult autopsy population. In 51 cases, one or more malignant neoplasms were associated; adenocarcinoma represented the most frequent histologic type of related neoplasm. Coagulation abnormalities suggestive of disseminated intravascular coagulation (DIC) were present in 18.5 per cent of the cases. It is possible that both the valvular and peripheral intravascular thromboses in at least some cases of NBTE represent the abnormal coagulation of DIC. Arterial thrombosis with infarction occurred in many peripheral organs. Splenic and renal were most frequent, but cerebral and cardiac consequences were the most significant.     

Bacterial pneumonia associated with corticosteroid therapy in three horses

Three horses developed severe pulmonary infections while being treated with systemic corticosteroids for other diseases. Two of them had an immune-mediated skin disease, compatible with a diagnosis of pemphigus foliaceus, and one had severe chronic obstructive pulmonary disease. Case 1 developed diffuse pneumonia from which Streptococcus zooepidemicus and Bacteroides melaninogenicus were isolated, and it responded to antibiotic therapy. Case 2 developed septicaemia, pulmonary thrombosis and pneumonia associated with Escherichia coli, and died during a peracute illness with signs of disseminated intravascular coagulation. Case 3 developed focal pneumonia from which S zooepidemicus was isolated. This horse was destroyed at the owner's request and no treatment was attempted.     

Interactions of mitochondrial ATP synthesis and the creatine kinase equilibrium in skeletal muscle

This study aimed to evaluate the effect of FR128998, (1s,6s)-1-benzyl-10-(3-pyridyl-methyl)-7-thia-10-azaspiro [5,6]-dodecan-11-one 7,7-dioxide hydrochloride, a novel platelet activating factor (PAF) receptor antagonist, on endotoxin lipopolysaccharide-induced disseminated intravascular coagulation in rats. Experimental disseminated intravascular coagulation was induced by an infusion of lipopolysaccharide at 0.25 mg/kg/h for 4 h. Simultaneous infusion of FR128998 (0.25 and 1.0 mg/kg/h) with lipopolysaccharide dose dependently inhibited thrombocytopenia, but not leukopenia. The changes in coagulation parameters of disseminated intravascular coagulation, i.e., prolongation of activated partial thromboplastin time and elevated levels of fibrinogen/fibrin degradation products, were also prevented by the treatment with FR128998. In addition, FR128998 attenuated the increase in serum tumor necrosis factor (TNF) which appeared during the initial stage of disseminated intravascular coagulation. FR128998 (10 microM) also inhibited the TNF production by peripheral blood leukocytes or alveolar macrophages stimulated by lipopolysaccharide in vitro. Furthermore, TNF production induced by PAF itself in vitro was also inhibited in the presence of FR128998. These data indicate that PAF plays a pivotal role in the development of disseminated intravascular coagulation via TNF production.     

Morphological and functional aspects of the cardiovascular system related to aging: does "aging heart" exist?

Thromboembolic disease (TE) is an important cause of in-hospital morbidity and mortality. The relationship between cancer and abnormalities of blood coagulation has been recognized for well over a century. Deep venous thrombosis (DVT) of the lower extremities is the most common cause of thromboembolic disease, but pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular coagulation, and other, more unusual, clinical events, may occur. Unexplained TE may serve as a marker for the presence of a hidden tumor. The frequency of pulmonary embolism (PE) among patients with a malignant neoplasm at necropsy is highly increased in the elderly patients. Among subjects with a malignant neoplasm, patients with pancreatic and gastric cancer (mucin-secreting adenocarcinomas), cancer of the large bowel and women with ovarian cancer had the highest frequency of PE. Old age, female sex, gastrointestinal and ovarian cancers must be considered as a significant risk factor for PE. The potentially responsible mechanisms for the thrombotic events, clinical manifestations, diagnostic implications and aspects of treatment of TE in malignant disease are discussed.     

Fine particulate organic material in the Los Angeles Basin-I: assessment of the high-volume Brigham Young University organic sampling system, BIG BOSS

BACKGROUND AND OBJECTIVE: Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. INFORMATION SOURCES: The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. STATE OF ART AND PERSPECTIVES: DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are required.