Plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected Northern elephant seals (Mirounga angustirostris).

BACKGROUND: Prepatent Otostrongylus arteritis results in hemorrhagic diathesis in free-ranging Northern elephant seals (Mirounga angustirostris) attributed to aberrant larval migration of the lungworm, Otostrongylus circumlitus. Clinical signs are often nonspecific, including lethargy, anorexia, and blepharospasm, but can progress to spontaneous frank hemorrhage and death within 72 hours of onset. Previously published case reports describe coagulopathy with prolonged PT and APTT, normal to elevated platelet counts, normal antithrombin concentrations, and low concentrations of fibrinogen degradation products. Disseminated intravascular coagulation was proposed as the cause of hemorrhage, but is inconsistent with some of the reported clinicopathologic changes. OBJECTIVE: The purpose of this study was to compare plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected elephant seals, in order to identify potential therapy. We hypothesized that hyperfibrinolysis contributed to hemorrhage in these cases. METHODS: Citrated plasma samples were collected from 3- to 4-month-old Northern elephant seals in a wildlife rehabilitation hospital. The sampled population included 25 healthy, prerelease seals and 32 clinically ill seals diagnosed with presumptive Otostrongylus arteritis. Twenty-one of the included seals had Otostrongylus infestation confirmed at necropsy. Standard coagulation tests and plasma thromboelastography were performed for a complete assessment of coagulation and fibrinolysis. RESULTS: Northern elephant seals with definitive Otostrongylus infestation were hypocoagulable and hypofibrinolytic compared to healthy controls. CONCLUSIONS: Results were most consistent with disseminated intravascular coagulation. Treatment with antifibrinolytic drugs to control hemorrhage may be unrewarding; alternative therapies such as plasma transfusions or coagulation factor concentrates should be investigated.

AN IMPORTED CASE OF COMPLICATED FALCIPARUM MALARIA.

The paper describes a clinical case of imported severe Pfalciparum malaria in a French citizen treated at the clinic of the Research Institute of Epidemiology, Microbiology, and Infectious Disdases, Ministry of the Republic of Uzbekistan. Due to the fact that the patient with tropical malaria sought medical advice too late, the disease was complicated by grade I malaria-induced coma, acute renal failure- in an oliguric phase, severe anemia, and disseminated intravascular coagulation syndrome. Thanks to effective etiopathogenetic and pathogenetic therapy, the patient recovered and returned to his motherland.

Coagulopathy in malaria.

Blood coagulation activation is frequently found in patients with malaria. Clinically apparent bleeding or disseminated intravascular coagulation (DIC) is associated with very severe disease and a high mortality. Protein C, protein S, and antithrombin levels were found to be low in P. falciparum, but were normal in P. vivax infection. Plasma levels of plasminogen activator inhibitor-1 were high in cases of P. falciparum infection whereas tissue plasminogen activator levels were low. Elevated plasma levels of von Willebrand factor (vWF) and vWF propeptide, thrombomodulin, endothelial microparticles have been reported in P. falciparum-infected patients. It has been demonstrated that severe P. falciparum infection is associated with acute endothelial cell (EC) activation, abnormal circulating ultralarge vWF multimers, and a significant reduction in plasma ADAMTS13 function. These changes may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease. It has also been shown that P. falciparum-parasitized red blood cells (pRBCs) induce tissue factor (TF) expression in microvascular ECs in vitro. Recently, loss of endothelial protein C receptor (EPCR) localized to sites of cytoadherent pRBCs in cerebral malaria has been demonstrated. Severe malaria is associated with parasite binding to EPCR. The cornerstone of the treatment of coagulopathy in malaria is the use of effective anti-malarial agents. DIC with spontaneous systemic bleeding should be treated with screened blood products. Study in Thailand has shown that for patients who presented with parasitemia >30% and severe systemic complications such as acute renal failure and ARDS, survival was superior in the group who received exchange transfusion. The use of heparin is generally restricted to patients with DIC and extensive deposition of fibrin, as occurs with purpura fulminans or acral ischemia. Antiplatelet agents interfere with the protective effect of platelets against malaria and should be avoided.

[Disseminated intravascular coagulopathy in a dog with Angiostrongylus vasorum infection]. / Disseminierte intravasale Koagulopathie bei einem Hund mit Angiostrongylus-vasorum-Infektion.

A 2-year-old female spayed Epagneul-Breton dog was presented with ecchymoses, but an undisturbed general condition. Clinical examination additionally revealed petechia and a haematoma. Travel history included Italy and Denmark. Laboratory abnormalities were moderate thrombocytopenia, prolonged PT, aPTT and TT, and elevated d-dimers. Initial therapy consisted of plasma transfusions, fluids, doxycycline and famotidine administration. Babesiosis, ehrlichiosis, leishmaniosis, dirofilariosis or anaplasmosis could not be confirmed. Abdominal ultrasound was unremarkable, while thoracic radiographs showed a bronchointerstitial pattern. Faecal samples collected over 3 days were positive for Angiostrongylus vasorum after examination using the Baermann lungworm test. The A. vasorum infection was successfully treated with fenbendazole, whereupon thrombocytopenia and prolonged coagulation times were resolved. In regions of low prevalence, an infection with A. vasorum should also be considered as a differential diagnosis in dogs with coagulation abnormalities. Respiratory signs can be absent with this disease. The patient may have acquired the infection abroad or in Germany.

Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy.

Thrombocytopenia develops early in malaria, but the underlying mechanisms remain incompletely understood. We studied the aetiology of malaria-associated thrombocytopenia in volunteers experimentally infected with Plasmodium falciparum malaria, in Indonesian malaria patients and in ex vivo studies. In experimental human malaria, the decrease in platelet counts was associated with a concurrent rise in young platelets (immature platelet fraction) and thrombopoietin. D-dimer concentrations were moderately elevated without a prolongation in the activated partial thromboplastin time or decrease in fibrinogen. There was no increase in expression of the platelet surface markers CD62P, PAC-1 and CD63 and in plasma concentrations of the platelet factors P-selectin, CXCR4, CXCL7, RANTES and CD40L. In contrast, concentrations of soluble glycoprotein-1b (sGP1b), the external domain of the platelet receptor for von Willebrand factor (VWF), increased early. Indonesian malaria patients also had elevated concentrations of sGP1b, which correlated with VWF concentrations. Finally, incubation of platelets with parasitized erythrocytes in vitro failed to induce platelet aggregation or activation. We concluded that neither compromised platelet production nor platelet activation or consumptive coagulopathy were responsible for the early thrombocytopenia in malaria. We hypothesize that the increase in sGP1b concentrations results from VWF-mediated GP1b shedding; a process that may prevent excessive adhesion of platelets and parasitized erythrocytes.

Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality.

OBJECTIVE: To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis. METHODS: In a prospective study, parameters of the coagulation system were measured on admission and during follow-up in 52 consecutive patients with severe leptospirosis. RESULTS: All patients showed coagulation disorders, such as prolonged prothrombin time (PT) and activated partial thromboplastin time, marked procoagulant activity [thrombin-antithrombin (TAT) complexes, prothrombin fragment 1+2, D-dimer], reduced levels of anticoagulant markers (protein C, antithrombin) and increased (anti-) fibrinolytic activity [plasmin-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1]. These disorders were more pronounced in patients who died eventually. PT prolongation was associated with mortality (OR 1.4, 95% CI: 1.0-1.8, P = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets

Blood coagulation, inflammation, and malaria.

Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article (i) reviews the literature related to blood coagulation and malaria in a historic perspective, (ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, (iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), (iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum infected patients, and (v) emphasizes the procoagulant role of parasitized red blood cells (RBCs) and activated platelets in the pathogenesis of malaria. This article also presents the Tissue Factor Model (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell (EC) activation, blood coagulation disorder, and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis.

Role of chronic disseminated intravascular coagulation in a case of canine angiostrongylosis.

A dog whose major clinical signs suggested a coagulopathy, is described. The dog had a history of bleeding episodes and had a severe regenerative anaemia. By using specific factor assays, the coagulopathy was found to be due to a consumptive intravascular process that resembled chronic disseminated intravascular coagulation. Subsequent investigations identified Angiostrongylus vasorum as the cause.

Disseminated toxoplasmosis in AIDS patients--report of 16 cases.

Between June 1986 and October 1992, disseminated toxoplasmosis was diagnosed in 16 AIDS patients. 13 cases were diagnosed at autopsy where multiple organ involvement was documented in all 13. Three patients were diagnosed intra vitam. All 3 survived with appropriate treatment. Clinical features indicative of disseminated toxoplasmosis were: fever of unknown origin between 39 degrees and 40 degrees C in 16 cases, clinical signs suggestive of sepsis or septic shock in 15, with progression to multiorgan failure in 10, disseminated intravascular coagulopathy in 6, confusion, disorientation or apathy in 13 and lack of a systemic pneumocystis carinii prophylaxis in all 16. Typical laboratory markers were: CD4 cell counts below 100 x 10(6)/l in 16 cases, elevation of serum lactic dehydrogenase in 16 and creatine phosphokinase (in 4/6), normal or only slightly elevated C-reactive protein (in 9/11), positive Toxoplasma gondii IgG antibodies in 15/16 and negative IgM antibodies in all 16. Lesions indicative of cerebral toxoplasmosis were visualized on cranial computerized tomography in only 3/10 evaluated patients. In patients with advanced HIV infection presenting with a systemic illness, including the clinical and laboratory features described above, systemic Toxoplasma gondii infection must be included in the differential diagnosis. In these patients, specific and if warranted, invasive diagnostic procedures followed by early vigorous therapeutic intervention should be considered.

[Pulmonary echinococcosis, hepatic opisthorchiasis and generalized trichinelliasis combined with pregnancy]. / Ekhinokokk legkikh, opistorkhoz pecheni, generalizovannyi trikhinellez v sochetanii s beremennost'iu.

A case is reported of a spontaneous abortion (25 weeks of gestation) in a Nenets woman resulting in thrombohemorrhagic syndrome and profuse uterine bleeding. The abortion is attributed to drastic allergization by three parasites: Echinococcus granulosus, Opisthorchis felineus, Trichinella spiralis.

Thrombocytopenia in leptospirosis: the absence of evidence for disseminated intravascular coagulation.

In a prospective study of human leptospirosis, thrombocytopenia was demonstrated in 54% of 24 cases. The only additional laboratory evidence suggestive of disseminated intravascular coagulation lay in a mild elevation of fibrinogen degradation products, but this occurred with equal frequency in nonthrombocytopenic patients. There is therefore no causal relationship between disseminated intravascular coagulation and the thrombocytopenia of human leptospirosis.

Thrombocytopenia in leptospirosis: the absence of evidence for disseminated intravascular coagulation

In a prospective study of human leptospirosis, thrombocytopenia was demonstrated in 54 percent of 24 cases. The only additional laboratory evidence suggestive of disseminated intravascular coagulation lay in a mild elevation of fibrinogen degradation products, but this occurred with equal frequency in nonthrombocytopenic patients. There is therefore no causal relationship between disseminated intravascular coagulation and the thrombocytopenia of human leptospirosis. (AU)

Experimental induction of a toxemia-like syndrome in the pregnant beagle.

A toxemia-like syndrome was induced in pregnant beagles by intraperitoneal inoculation of concentrates prepared from placentas of patients with preeclampsia-eclampsia and hydatidiform mole, which contained an agent, Hydatoxi lualba, that stained in a unique fashion with toluidine blue-O-. The pregnant dogs inoculated with either of these concentrates progressively developed hypertension, eyeground changes consistent with hypertensive retinopathy, proteinuria, disseminated intravascular coagulation, and hepatic dysfunction in addition to intrauterine growth retardation and intrauterine fetal death. Hepatic periportal hemorrhage and glomeruloendotheliosis, lesions usually seen in preeclampsia-eclampsia, were also noted to occur in pregnant beagles inoculated with these concentrates. A significant increased sensitivity to angiotensin II infusion was also noted. The toxemia-like syndrome did not develop in pregnant beagles when inoculated in a similar fashion with concentrates prepared from placentas from normal term pregnancies which were free of Hydatoxi lualba or in nonpregnant beagles inoculated with concentrates containing Hydatoxi lualba. Although the agent was not injected in pure form, the inoculation of concentrates containing Hydatoxi lualba appears to be required for the manifestation of the toxemia-like syndrome.