Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review.

BACKGROUND: The desert horned vipers (Cerastes cerastes and C. gasperettii) are the most familiar snakes of the great deserts of North Africa and the Middle East, including the plains of Iraq. They are responsible for many human snake bites. In Western countries, they are popular among exotic-snake keepers. AIM: To investigate mechanisms of life-threatening envenoming and treatment. DESIGN: Clinical investigation. METHODS: Clinical and laboratory studies with measurement of serum venom antigen concentrations by enzyme immunoassay. RESULTS: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure. The clinical picture is explicable by the presence in C. cerastes venom of several thrombin-like, Factor-X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In one case, prophylactic use of subcutaneous epinephrine may have contributed to intracranial haemorrhage. The roles in treatment of heparin (rejected) and specific antivenom (recommended) are discussed. DISCUSSION: Cerastes cerastes is capable of life-threatening envenoming in humans. Optimal treatment of envenoming is by early administration of specific antivenom, and avoidance of ineffective and potentially-dangerous ancillary methods.

Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients.

Beriplex, a prothrombin complex concentrate (PCC), was administered to 42 patients requiring immediate reversal of their oral anticoagulant therapy. The dose administered was determined using the pretreatment International Normalized Ratio (INR). Blood samples were obtained before treatment and at 20, 60 and 120 min after treatment. The following investigations were performed on all samples - INR, clotting factors II, VII, IX and X, coagulation inhibitors protein C (PC) and antithrombin (AT), and other markers of disseminated intravascular coagulation, plasma fibrinogen, D-dimer and platelet count. Immediate reversal of the INR, the vitamin K-dependent clotting factors and PC was achieved in virtually all patients. Reduced AT levels were present in 18 patients before treatment. Further slight AT reductions occurred in four patients, but other associated abnormalities of haemostasis were observed in only one of the four patients. One patient with severe peripheral vascular disease, sepsis and renal and cardiac failure died of a thrombotic stroke following leg amputation, 48 h after receiving Beriplex. No other arterial and no venous thromboembolic events occurred within 7 d of treatment. Beriplex is effective in rapidly reversing the anticoagulant effects of warfarin, including PC deficiency, without inducing coagulation activation. Caution should continue to be exercised in the use of these products in patients with disseminated intravascular coagulation, sepsis or liver disease.

Immune hemolytic anemia due to diclofenac.

A 37-year-old male presented with severe anemia, mild jaundice, and hemoglobinuria during his second course of diclofenac for gout. The peripheral blood showed microspherocytes and nucleated red blood cells (RBCs). The reticulocyte count was 21 percent and haptoglobin was < 0.1 g/L. A presumptive diagnosis of diclofenac-induced immune hemolysis was made and blood, urine, and drug samples were referred for investigation. Direct antiglobulin testing showed the RBCs to be coated with IgG1, IgG4, and C3d, but an eluate only yielded weakly reacting IgG antibodies. In tests for drug-dependent antibodies, group O, R1R2 red cells were incubated with the patient's serum that had been mixed with either urine (which contained diclofenac metabolites) or diclofenac solution and then tested by an antiglobulin method. Strongly positive reactions with anti-IgG occurred in the tests using urine but only weak reactions in those tests employing diclofenac solution. All controls gave negative results. These findings support the role of diclofenac in causing hemolysis and the importance of employing urine as a source of drug metabolites. The findings also showed that an immune complex mechanism predominated and that the eluted IgG (detectable independently of the presence of the drug or its metabolites) confirmed a minor autoimmune component. Diclofenac was stopped and treatment with prednisolone and folic acid instituted; this resulted in complete recovery.