Reinstituting warfarin in patients who develop warfarin skin necrosis.

Skin necrosis is a rare but serious complication of oral anticoagulation with coumarin derivatives. Frequently, the necrosis can be extensive and may result in major morbidity and mortality. The majority of these patients require prolonged anticoagulation for life-threatening conditions such as deep various thrombosis and pulmonary embolism. Resuming oral anticoagulants in the face of skin necrosis is a difficult decision for both the patient and the physician. Because long-term heparin therapy is inconvenient and is associated with significant side effects, we reviewed the literature to find alternative treatment strategies. A Medline search was done, and all papers published in English since 1967 were reviewed. Of 58 cases with skin necrosis attributed to oral anticoagulants, oral anticoagulation was resumed in 7 patients with no resulting adverse effects. Warfarin is the most widely used coumarin derivative in the United States. Based on our review, we make recommendations for resuming warfarin in patients who have developed skin necrosis when the clinical condition absolutely requires prolonged anticoagulation.

Fatal thrombocytopenic coagulopathy after cardiopulmonary bypass: clinicopathologic correlations implicating heparin.

Heparin-associated thrombotic thrombocytopenia after cardiopulmonary bypass is frequently lethal. The propensity for this syndrome generally goes unrecognized because thrombocytopenia is common in the early postoperative period and because testing for heparin-induced platelet antibody may not distinguish between patients with thrombocytopenia alone and those in whom associated thrombi (the white clot syndrome) may develop. Moreover, differentiation between heparin-associated thrombotic thrombocytopenia and a consumptive coagulopathy may be difficult, and intervention may be inappropriate because of diametrically opposite treatments. Our experience with three cases and the necropsy findings in two of them demonstrate that postbypass thrombocytopenic coagulopathy may be a clinical and pathologic spectrum of consumptive coagulopathy, with heparin as the major premorbid factor. This report further emphasizes the need for vigilance in assessing certain patients preoperatively to lessen the high risk of morbidity and mortality associated with this syndrome.

When a patient with a bleeding disorder needs dental work. How you can work with the dentist to prevent a crisis.

Patients with bleeding disorders need close cooperation between their physician and their dental practitioner to receive safe, comprehensive dental care. When indicated, physicians must advise a compromised treatment plan to avoid deep injections or surgical procedures that may initiate a bleeding crisis in patients at risk. The conditions most commonly seen that require special consideration are long-term use of antithrombotic agents, platelet dysfunction caused by chronic renal failure, and congenital clotting factor deficiencies. Even these patients may undergo a high-risk procedure, such as periodontal surgery, with adequate precautions and preparation.

Streptokinase therapy for deep vein thrombosis: a comprehensive review of the English literature.

A comprehensive review of the English literature evaluating streptokinase (SK) in the treatment of deep venous thrombosis (DVT) of the lower extremity reveals complete lysis of thrombi in as many as 70% of patients studied. The degree of lysis is affected by duration of symptoms before treatment, degree of occlusion, thrombus location, and development of a plasma proteolytic state. SK-treated patients have not been found to have a greater incidence of major hemorrhagic complications when compared with heparin-treated patients. SK is clearly beneficial in the treatment of DVT if patients are properly selected and carefully managed. Proper patient selection and a recommended treatment protocol are described.

Hb Evans or alpha 262(E11)Val----Met beta 2; an unstable hemoglobin causing a mild hemolytic anemia.

Structural analysis of the alpha chain of the hemoglobin from a Caucasian female with a mild hemolytic anemia showed the presence of a variant with a Val----Met substitution at position alpha 62. The valine at this position forms one of the contacts with heme and its replacement by methionine will likely decrease heme binding and cause a distortion of the heme crevice and a decreased stability of the abnormal protein. Dot-blot analysis of amplified DNA with 32P-labeled synthetic oligonucleotide probes confirmed the suspected G----A mutation in the first position of codon 62, and also located the mutation in the alpha 2-globin gene. The mutation was found in the proposita and one of her daughters but was most probably absent in her parents.

Desensitization to factor VIII in a patient with classic hemophilia and C2 deficiency.

Factor VIII therapy has been reported to cause anaphylactic reactions in patients with hemophilia. Desensitization attempts have been complicated by severe allergic reactions that have prevented the achievement of protective factor VIII levels. We report successful administration of factor VIII by a graded dose desensitization protocol in a 36-year-old man with hemophilia A who had previously experienced anaphylactic reactions to factor VIII infusions. The reactions were manifested by urticaria, choking, and bronchospasm and were not prevented by pretreatment with antihistamines and corticosteroids. Intradermal skin test with factor VIII was positive. Serum levels of circulating immune complexes were slightly elevated. Persistently low serum C2 levels were consistent with genetic C2 deficiency. These findings suggest the possibility of Type I (IgE mediated) and Type III (immune complex) immunopathogenic mechanisms. Our experience suggests that administration of factor VIII by graded dose desensitization protocol may offer a practical therapeutic approach for management of hemorrhage in patients with classic hemophilia who are allergic to factor VIII.

Lack of toxicity of oral and intrapulmonary group B streptococcal lipoteichoic acid.

Lipoteichoic acid (LTA) was prepared from type III group B streptococci and administered by topical oral application or intravenous or intratracheal injection in weanling and adult white New Zealand rabbits. Tritiated [3H]LTA in tissues and body fluids was measured by scintillation spectrometry. Five minutes to 120 h after intravenous injection of 10 mg (17 x 10(6) dpm) of [3H]LTA, none was present in blood. Combined urine and fecal excretion peaked at 24 h and decreased over 5 days. There was no effect on collagen-induced platelet aggregation. [3H]LTA concentrations were greatest in colon, bone, stomach, and skin 1 day after intravenous injection. After a 5-mg oral dose (8.5 x 10(6) dpm) in an adult animal, fecal excretion peaked at 24 h and decreased after 4 days. No systemic absorption was noted. No [3H]LTA was found in any of seven tissues examined at autopsy 3 days after 1 to 5 mg/kg oral doses in weanling animals with normal or traumatized buccal mucosa. No effect was noted on platelet aggregation or serum complement, there was no increase in the incidence of nephrocalcinosis and the buccal mucosa remained histologically normal. Intratracheal injection of 0.5 to 2.5 mg/kg of LTA resulted in no tachypnea or alteration in blood gases. All animals remained healthy after LTA administration. The absence of toxicity and absorption in animals suggests that studies could be performed in humans to evaluate the safety and efficacy of oral LTA.

Partial characterization of an erythropoiesis inhibitory factor.

An inhibitory factor of erythropoiesis, obtained from normal human urine, is indicated to be a complex of a fragment of alpha 1-acid glycoprotein and prostaglandin F2 alpha. Immunoelectrophoresis reveals two protein components in the EIF complex which separate during acrylamide gel electrophoresis. A gamma-globulin (MW 185,000) is a carrier of the complex. A fragment of alpha 1-acid glycoprotein (MW 9300) retains the inhibitory factor, PGF2 alpha. Noncovalent forces bind the PGF2 alpha to the protein, and PGF2 alpha can be extracted with benzene.

Unregulated production of virus and/or sperm specific anti-idiotypic antibodies as a cause of AIDS.

A network of idiotypic and anti-idiotypic antibodies is often suggested as the basis for cellular interactions that maintain a steady-state immunological equilibrium. This hypothesis proposes that repeated exposure to certain external antigens--ie, both viral and sperm--stimulates an unregulated production of a uniquely potent immunomodulating idiotypic antibody(ies). In a genetically predisposed individual, this particular antibody(ies), which is also an autoantibody(ies), results in a cellular immune deficiency. This disruption in the immune system permits opportunistic infection and thus the acquired immune deficiency syndrome. This hypothesis, which is readily testable and which does not involve a primary pathogen, can explain both the active induction of this disease in, as well as its passive transfer to, all at-risk populations.

Chronic erythroid hyperplasia and accelerated bone turnover.

Bone atrophy is generally thought to be the etiology of the decreased skeletal mass and fractures found in patients with ineffective hematopoiesis and associated erythroid hyperplasia. A bone biopsy from a patient with chronic erythroid hyperplasia and diffuse cortical osteopenia revealed a normal trabecular bone volume, excess osteoid, numerous osteoblasts, and increased osteoclastic resorptive surface. The increased fractional labeled surfaces and widely spaced double tetracycline labels indicated accelerated bone turnover, despite demonstrable iron deposits at the calcification front and cement lines and a low serum level of 25-hydroxyvitamin D. The relationship between the expanded marrow space and trabecular bone suggests that local marrow factors may be responsible for the rapid bone remodeling.

Inhibition of Friend virus (FVP)-induced murine erythropoiesis with prostaglandin (PGF2 alpha): potentiation and inhibition of erythropoietin and prevention of both with PGD2.

An erythropoietin-independent virus-induced murine erythroleukemia (FVP) is used to compare the effects of an erythropoiesis inhibitory factor (EIF) isolated from human urine with the effects of prostaglandin F2 alpha. The consequent inhibition of FVP-induced erythropoiesis suggests that EIF and PGF2 alpha have similar effects on the FVP-induced erythropoiesis in mice, and the effect of PGF2 alpha is indirect. The similarity of the actions of EIF and PGF2 alpha may indicate a potential role for prostaglandins in the physiological control of some types of erythrocytosis.

Effect of intraarterial injection of heparin on the complications of percutaneous arterial catheterization in infants and children.

Thrombotic complications of percutaneous arterial catheterization still remain a significant and serious problem in infants and children. Systemic heparinization has been recommended for prevention of these complications. The purpose of this study was to evaluate the effect of intraarterial injection of heparin in reducing thrombotic complications following percutaneous femoral artery catheterization. One hundred sixteen consecutive patients (ages four months to 20 years) studied by the Desilets-Hoffman modification of Seldinger's technique of femoral artery catheterization were randomly allocated to the control or heparin groups using a double-blind technique. At the completion of the catheterization, 0.1 mg/kg of placebo or heparin (1,000 units/ml) was injected into the common iliac artery prior to removal of the catheter and sheath. Segmental plethysmography was performed in both lower extremities prior to and after the catheterization, and a plethysmography index (PI) was calculated. The age and sex distribution, diagnoses, number, type, and site of previous catheterization, hemoglobin, platelet count, the amount of flush solution and the heparin contained therein, size of the catheter and sheath used, number of arterial punctures, and the length of the time in the artery were similar in the two groups (P greater than 0.1). Thrombin time and activated partial thromboplastin time were measured prior to the use of flush solution and prior to angiography, and these remained essentially unchanged in the two groups. The PI in the control group (97.5 +/- 320 was not significantly different (P greater than 0.1) from that of the heparin group (97.7 +/- 32). Similarly, the six to 24 month of postcatheterization plethysmography data show no differences (P greater than 0.1). The number of patients with reduced ipsilateral posterior tibial and dorsalis pedis pulses was also similar (P greater than 0.1). None of the patients in either group required thrombectomy. The low low incidence of arterial complications in our patients when compared with other studies may be related in part to the use of a sheath, which is not called for in original Seldinger technique. The data suggest that full-dose heparin administration does not significantly alter arterial complications following percutaneous femoral artery catheterization, especially in children over five years of age.

Inhibition of erythropoiesis by plasma component(s) from sheep, goats, and rabbits.

Plasma from hypertransfused and normal sheep and experimentally induced anemic and normal goats was fractionated by ultrafiltration. Fractions obtained were assayed for erythropoiesis stimulatory factor (ESF) or erythropoiesis inhibitory factor (EIF) activity (or both) in the posthypoxic polycythemic mouse assay. The most potent sheep plasma-inhibitor fraction was found in the retentate on a membrane with a cutoff at mol wt 50,000. The most potent EIF fraction from anemic goats passed into the ultrafiltrate, but the comparable EIF from normal goats remained in the retentate on a membrane with a cutoff at mol wt 500. The yield of the most potent EIF fraction was higher from anemic goats than was the yield from normal goats. During thin-layer chromatography, EIF extracted from goat plasma fractions had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction IV-4 had an inhibitory factor, and a benzene extract of the fraction contained a component that had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction V contained a component that potentiated an erythropoietin-generating factor.