Biomedical subjects

M C Coots

Publications and source records attributed to M C Coots.

9 recordsLinked to original sources

PubMed1992

Protein S deficiency and skin necrosis associated with continuous ambulatory peritoneal dialysis.

Skin necrosis associated with protein C deficiency has recently been reported to occur in hemodialysis patients. The clinical presentation and course of this syndrome appears indistinguishable from skin necrosis (purpura fulminans) seen in other settings with inherited or acquired deficiency of the naturally occurring anticoagulant proteins, protein C and S. Patients on maintenance hemodialysis may have low levels of these factors. However, patients on peritoneal dialysis have normal or elevated levels of these proteins despite documented peritoneal losses. We report two patients in whom the occurrence of protein S deficiency and subsequent skin necrosis can be related to demonstrated peritoneal dialysis-associated losses. We suggest that these losses may become critical under appropriate conditions and suggest caution in peritoneal dialysis patients requiring warfarin therapy.

Blood Proteins↗

PubMed1990

The persistence and heterogeneity of factor VIII:C inhibitors as demonstrated by preparative isofocusing.

The purpose of this study was to determine if factor VIII:C inhibitors completely disappear during remission and if they recur on exacerbation, are they similar to or different from the original inhibitors? To answer these questions, isofocusing, which separates proteins on the basis of their pIs, was utilized to recover inhibitors from the plasmas of six patients, five nonhemophiliacs with acquired VIII:C inhibitors and the sixth with classic hemophilia. Initially, all plasmas were studied during the presenting hemorrhagic episodes and, subsequently, following the disappearance or recurrence of the inhibitors. Following isofocusing, each fraction was tested for inhibitory activity. The method enabled us to determine that inhibitors to factor VIII:C persisted even when they could not be demonstrated by conventional methods. The inhibitory activity resulted from a composite of inhibitors, each of the group identified by its own pI. In many patients, some peaks persisted throughout the entire interval of study, whereas others disappeared and new ones appeared, suggesting that various groups of cells were capable of producing the inhibitors.

Aged↗

PubMed1989

A monoclonal immunoglobulin A (kappa) factor VIII:C inhibitor associated with primary amyloidosis: identification and characterization.

Factor VIII:C inhibitors associated with primary amyloidosis have not been previously reported. A patient with autopsy-proved primary amyloidosis developed renal failure requiring peritoneal dialysis. Purpura and a prolonged partial thromboplastin time (PTT) were first observed 3 years later, after treatment was changed from peritoneal dialysis to hemodialysis. Plasma contained a time-dependent factor VIII:C inhibitor. The inhibitor on isoelectric focusing showed two peaks of activity, one with an isoelectric point (pl) of approximately 4 and the second larger, with a pl of approximately 8. Both were neutralized only by antisera to IgA and kappa light chain. A monoclonal antibody prepared in Balb/c mice against the variable region of the kappa light chain also blocked the inhibitor. The delayed onset of the coagulopathy could be explained by the change from peritoneal to hemodialysis, because in the former, significant amounts of the paraprotein, indicated by an "M-spike," were recovered in the dialysate. N-terminal amino acid sequencing of the first 20 amino acids of the variable region of the kappa light chain from the urinary protein and the splenic amyloid subunit showed identity.

Amino Acid Sequence↗

PubMed1987

An acquired inhibitor to factor VIIIC in a non-hemophiliac: twenty years of observation and characterization.

A non-hemophilic patient with an acquired inhibitor to factor VIIIC was initially diagnosed in this laboratory 20 years ago at age 63. Following its initial appearance in 1963, the inhibitor was detectable on two other occasions. We believe that this is the longest duration such an inhibitor has persisted. No sample remained from his initial admission; however, samples were available from the last 8 years of his life for retrospective study. Preparative isofocusing, affinity chromatography, and immunoglobulin subtyping were used to determine the similarities and/or differences in the inhibitor over these 8 years. The following similarities and differences were observed in both the 1975 and 1983 plasmas. Isofocusing showed that both plasmas contained peaks of inhibitory activity with pIs of 7.25, 8.26, and 8.88; the 1975 sample in addition contained two peaks with pIs of 7.77 and 9.45, whereas two other peaks with pIs of 7.64 and 7.85 were found in the 1983 sample. For the final characterization, each isofocused inhibitory peak was eluted from Protein A Sepharose and incubated with antisera to determine the immunoglobulin subtype. Each peak consisted of mixtures of IgG1 and IgG4 with both kappa and lambda light chains. It was concluded that the inhibitor was polyclonal, based on the presence of inhibitory peaks with different pIs and immunoglobulin subtypes. These findings support the conclusion that the development of and changes in the inhibitor was a dynamic process with some inhibitors (antibodies) persisting, while at the same time others with different characteristics were being formed.

Chromatography, Affinity↗

PubMed1985

Agarose gel method: its usefulness in assaying factor VIII inhibitors, evaluating treatment and suggesting a mechanism of action for factor IX concentrates.

Plasmas from 14 patients with factor VIII inhibitors, 10 haemophiliacs and four non-haemophiliacs, were assayed by both the agarose gel and Bethesda methods. Good correlation was observed in 34 samples from 13 patients, but there was poor correlation in three samples from a single haemophilic patient. The sensitivity of the method was increased by diluting normal platelet rich plasma (PRP) with congenital factor VIII deficient plasma. With this modification, as little as 0.4 of a Bethesda unit (Bu) could be measured accurately. The agarose method is easier to perform and requires much less technician time than the Bethesda assay (Ba). Inhibitory activity can be measured even in the presence of large amounts of transfused factor VIII or factor IX concentrates. To study the effect of factor IX concentrates on the inhibitor, the method was modified by incorporating into the gels plasmas specifically deficient in either factor VII, IX or X. Our data suggest that factor VII is probably responsible for the 'bypassing' activity of factor IX concentrates.

Factor IX↗

PubMed1979

An acquired abnormal fibrinogen associated with thromboembolic disease and pseudotumor cerebri.

An abnormal fibrinogen was found in a patient associated with disabling recurrent phlebitis and pulmonary emboli, pseudotumor cerebri, gout and endometriosis. The fibrinogen is characterized by (1) abnormal side-to-side and end-to-end polymerization, (2) abnormal fibrinopeptide release, (3) a delayed gamma-gamma dimerization of the non cross-linked fibrin, (4) a pH optimum of 7--7.8, and (5) a deviation from normal amino acid composition with regard to lysine, aspartic acid, glutamic acid and serine. Since no defect has been found in any of her three children, and since the prothromin and partial thromboplastin times vary from time to time, it is assumed that the defect is acquired. Liver disease, usually associated with acquired abnormal fibrinogen, has been excluded as an etiological cause since liver function tests and biopsy are completely normal.

Amino Acids↗

PubMed1979

A factor V inhibitor: in vitro interference by calcium.

A patient with a factor V inhibitor resistant to all standard methods of therapy was recently reported. Because of this resistance, further investigation of the inhibitor was carried out employing the inhibitory plasma, serum, and isofocused fraction. It has subsequently been shown in vitro by use of the prothrombin time, partial thromboplastin time, and Russell's viper venom time that the activity of the inhibitor is diminished by the addition of calcium chloride or calcium gluconate to the inhibitory plasma, serum, or isofocused fraction before the addition of normal pooled plasma. This inhibitor, an IgG4 (lambda) immunoglobulin appears to have a high calcium binding affinity and is markedly potentiated in acid pH. These findings suggest that there may be a role in vivo for calcium infusion as part of the clinical management of such an inhibitor and that the metabolic acidosis associated with hemorrhagic shock may potentiate this type of inhibitor.

Calcium↗

PubMed1979

A monoclonal IgG4 (lambda) with factor V inhibitory activity.

A monoclonal IgG4 (lambda) with inhibitory activity to human coagulation factor V was isolated from the serum of a patient with a fatal hemorrhagic diathesis by using a combination of DE-52 ion exchange chromatography and isoelectric focusing techniques. Using the criteria for defining a monoclonal immunoglobulin of restricted mobility on protein electrophoresis, immunoelectrophoresis, and isoelectric focusing, as well as neutralization with class, subclass, and light chain type antisera, we are the first to demonstrate a factor V inhibitor as a monoclonal IgG4 (lambda) detectable in serum or plasma.

Chromatography, Ion Exchange↗

PubMed1978

Hemorrhagic death associated with a high titer factor V inhibitor.

An acquired bleeding diathesis was first noted in a 51-year-old patient 11 days following an exploratory laparotomy. Laboratory studies indicated the cause of bleeding to be the development of a circulating anticoagulant which inhibited factor V activity. The inhibitor, an immunoglobulin of the IgG class, was separated by use of Sephadex G-200 filtration, disc electrophoresis, and isoelectric focusing. Despite vigorous immunosuppressive, antifibrinolytic, and replacement therapy, including the use of a "prothrombin complex" and plasmaphoresis, the bleeding diathesis could not be reversed and the patient died of hemorrhage. Although inhibitors to factor V are not usually associated with major life-threatening hemorrhage, this case demonstrates that the development of such an inhibitor can be an ominous finding. The use of an aminoglycoside antibiotic in this and other patients so reported may be one of the contributing causes to the development of such an inhibitor.

Antibodies↗